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Sample records for vldl lipolysis products

  1. VLDL lipolysis products increase VLDL fluidity and convert apolipoprotein E4 into a more expanded conformation.

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    Tetali, Sarada D; Budamagunta, Madhu S; Simion, Catalina; den Hartigh, Laura J; Kálai, Tamás; Hideg, Kálmán; Hatters, Danny M; Weisgraber, Karl H; Voss, John C; Rutledge, John C

    2010-06-01

    Our previous work indicated that apolipoprotein (apo) E4 assumes a more expanded conformation in the postprandial period. The postprandial state is characterized by increased VLDL lipolysis. In this article, we tested the hypothesis that VLDL lipolysis products increase VLDL particle fluidity, which mediates expansion of apoE4 on the VLDL particle. Plasma from healthy subjects was collected before and after a moderately high-fat meal and incubated with nitroxyl-spin labeled apoE. ApoE conformation was examined by electron paramagnetic resonance spectroscopy using targeted spin probes on cysteines introduced in the N-terminal (S76C) and C-terminal (A241C) domains. Further, we synthesized a novel nitroxyl spin-labeled cholesterol analog, which gave insight into lipoprotein particle fluidity. Our data revealed that the order of lipoprotein fluidity was HDL approximately LDL<VLDL+lipoprotein lipase. Moreover, the conformation of apoE4 depended on the lipoprotein fraction: VLDL-associated apoE4 had a more linear conformation than apoE4 associated with LDL or HDL. Further, by changing VLDL fluidity, VLDL lipolysis products significantly altered apoE4 into a more expanded conformation. Our studies indicate that after every meal, VLDL fluidity is increased causing apoE4 associated with VLDL to assume a more expanded conformation, potentially enhancing the pathogenicity of apoE4 in vascular tissue.

  2. Postprandial apoE isoform and conformational changes associated with VLDL lipolysis products modulate monocyte inflammation.

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    Laura J den Hartigh

    Full Text Available Postprandial hyperlipemia, characterized by increased circulating very low-density lipoproteins (VLDL and circulating lipopolysaccharide (LPS, has been proposed as a mechanism of vascular injury. Our goal was to examine the interactions between postprandial lipoproteins, LPS, and apoE3 and apoE4 on monocyte activation.We showed that apoE3 complexed to phospholipid vesicles attenuates LPS-induced THP-1 monocyte cytokine expression, while apoE4 increases expression. ELISA revealed that apoE3 binds to LPS with higher affinity than apoE4. Electron paramagnetic resonance (EPR spectroscopy of site-directed spin labels placed on specific amino acids of apoE3 showed that LPS interferes with conformational changes normally associated with lipid binding. Specifically, compared to apoE4, apoE bearing the E3-like R112→Ser mutation displays increased self association when exposed to LPS, consistent with a stronger apoE3-LPS interaction. Additionally, lipolysis of fasting VLDL from normal human donors attenuated LPS-induced TNFα secretion from monocytes to a greater extent than postprandial VLDL, an effect partially reversed by blocking apoE. This effect was reproduced using fasting VLDL lipolysis products from e3/e3 donors, but not from e4/e4 subjects, suggesting that apoE3 on fasting VLDL prevents LPS-induced inflammation more readily than apoE4.Postprandial apoE isoform and conformational changes associated with VLDL dramatically modulate vascular inflammation.

  3. Impact of phosphatidylcholine liposomes on the compositional changes of VLDL during lipoprotein lipase (LPL)-mediated lipolysis.

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    Ćwiklińska, Agnieszka; Gliwińska, Anna; Senderowska, Zuzanna; Kortas-Stempak, Barbara; Kuchta, Agnieszka; Dąbkowski, Kamil; Jankowski, Maciej

    2016-02-01

    Lipoprotein lipase (LPL)-mediated triacylglycerol (TAG) hydrolysis in very low density lipoprotein (VLDL) is accompanied by the release of surface material containing phospholipids (PL), free cholesterol (FC) and apolipoproteins, E (apoE) and Cs (apoCII, apoCIII). The released molecules are accepted by high density lipoprotein (HDL), and new HDL-sized apoE-containing particles are also generated. A decrease in the number of HDL particles or abnormalities in their structure is associated with unfavourable changes in the features of VLDL remnants. Phosphatidylcholine liposomes (PC-L) can also act as acceptors of surface material components released from lipoproteins. Thus, the aim of this study was to assess the impact of liposomes on compositional changes of VLDL during its LPL-mediated lipolysis. VLDL isolated from human sera was incubated with LPL (LPL:VLDLTAG; 24 μg/ml:90 mg/dl) and/or PC-L (VLDLPL:PC-LPL; 1:30 weight ratio). After incubation (2h, 37 °C) VLDL was separated from other reaction products, and VLDL lipid and apolipoprotein content were analysed. Newly generated HDL-sized apoE-containing lipoproteins were separated by two-dimensional non-denaturing gradient gel electrophoresis (2D-PAGGE). The reaction of VLDL with PC-L in the presence or absence of LPL significantly affected the VLDL composition. The ratio of core (TAG+cholesteryl ester) to surface (PL+FC) lipids in VLDL decreased 1.8-fold with PC-L, 1.2-fold with LPL and 3-fold with PC-L+LPL. The reaction with PC-L and PC-L+LPL caused a 3.7-fold and 3.2-fold decrease of apoCs/apoE average weight ratio, respectively. Compositional changes in VLDL under the influence of PC-L were accompanied by an increase in the efficiency of VLDL lipolysis and the generation of apoE-containing HDL-sized particles, heterogeneous in size (from ∼ 9 to ∼ 18.8 nm) and mobility (γ and preβ). We conclude that PL-rich particles, similarly to HDL, promote the release of surface material components from VLDL during LPL

  4. VLDL-activated cell signaling pathways that stimulate adrenal cell aldosterone production.

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    Tsai, Ying-Ying; Rainey, William E; Johnson, Maribeth H; Bollag, Wendy B

    2016-09-15

    Aldosterone plays an important role in regulating ion and fluid homeostasis and thus blood pressure, and hyperaldosteronism results in hypertension. Hypertension is also observed with obesity, which is associated with additional health risks, including cardiovascular disease. Obese individuals have high serum levels of very low-density lipoprotein (VLDL), which has been shown to stimulate aldosterone production; however, the mechanisms underlying VLDL-induced aldosterone production are still unclear. Here we demonstrate in human adrenocortical carcinoma (HAC15) cells that submaximal concentrations of angiotensin II and VLDL stimulate aldosterone production in an additive fashion, suggesting the possibility of common mechanisms of action. We show using inhibitors that VLDL-induced aldosterone production is mediated by the PLC/IP3/PKC signaling pathway. Our results suggest that PKC is upstream of the extracellular signal-regulated kinase (ERK) activation previously observed with VLDL. An understanding of the mechanisms mediating VLDL-induced aldosterone production may provide insights into therapies to treat obesity-associated hypertension.

  5. VLDL hydrolysis by LPL activates PPAR-alpha through generation of unbound fatty acids.

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    Ruby, Maxwell A; Goldenson, Benjamin; Orasanu, Gabriela; Johnston, Thomas P; Plutzky, Jorge; Krauss, Ronald M

    2010-08-01

    Recent evidence suggests that lipoproteins serve as circulating reservoirs of peroxisomal proliferator activated receptor (PPAR) ligands that are accessible through lipolysis. The present study was conducted to determine the biochemical basis of PPAR-alpha activation by lipolysis products and their contribution to PPAR-alpha function in vivo. PPAR-alpha activation was measured in bovine aortic endothelial cells following treatment with human plasma, VLDL lipolysis products, or oleic acid. While plasma failed to activate PPAR-alpha, oleic acid performed similarly to VLDL lipolysis products. Therefore, fatty acids are likely to be the PPAR-alpha ligands generated by VLDL lipolysis. Indeed, unbound fatty acid concentration determined PPAR-alpha activation regardless of fatty acid source, with PPAR-alpha activation occurring only at unbound fatty acid concentrations that are unachievable under physiological conditions without lipase action. In mice, a synthetic lipase inhibitor (poloxamer-407) attenuated fasting-induced changes in expression of PPAR-alpha target genes. Apolipoprotein CIII (apoCIII), an endogenous inhibitor of lipoprotein and hepatic lipase, regulated access to the lipoprotein pool of PPAR-alpha ligands, because addition of exogenous apoCIII inhibited, and removal of endogenous apoCIII potentiated, lipolytic PPAR-alpha activation. These data suggest that the PPAR-alpha response is generated by unbound fatty acids released locally by lipase activity and not by circulating plasma fatty acids.

  6. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet.

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    van Diepen, Janna A; Vroegrijk, Irene O C M; Berbée, Jimmy F P; Shoelson, Steven E; Romijn, Johannes A; Havekes, Louis M; Rensen, Patrick C N; Voshol, Peter J

    2011-12-01

    Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-κB activity but also reduces hypertriglyceridemia in humans. The aim of this study was to investigate the mechanism by which aspirin improves hypertriglyceridemia. Human apolipoprotein CI (apoCI)-expressing mice (APOC1 mice), an animal model with elevated plasma triglyceride (TG) levels, as well as normolipidemic wild-type (WT) mice were fed a high-fat diet (HFD) and treated with aspirin. Aspirin treatment reduced hepatic NF-κB activity in HFD-fed APOC1 and WT mice, and in addition, aspirin decreased plasma TG levels (-32%, P < 0.05) in hypertriglyceridemic APOC1 mice. This TG-lowering effect could not be explained by enhanced VLDL-TG clearance, but aspirin selectively reduced hepatic production of VLDL-TG in both APOC1 (-28%, P < 0.05) and WT mice (-33%, P < 0.05) without affecting VLDL-apoB production. Aspirin did not alter hepatic expression of genes involved in FA oxidation, lipogenesis, and VLDL production but decreased the incorporation of plasma-derived FA by the liver into VLDL-TG (-24%, P < 0.05), which was independent of hepatic expression of genes involved in FA uptake and transport. We conclude that aspirin improves hypertriglyceridemia by decreasing VLDL-TG production without affecting VLDL particle production. Therefore, the inhibition of inflammatory pathways by aspirin could be an interesting target for the treatment of hypertriglyceridemia.

  7. Hepatocyte-specific IKK-β activation enhances VLDL-triglyceride production in APOE*3-Leiden mice.

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    van Diepen, Janna A; Wong, Man C; Guigas, Bruno; Bos, Jasper; Stienstra, Rinke; Hodson, Leanne; Shoelson, Steven E; Berbée, Jimmy F P; Rensen, Patrick C N; Romijn, Johannes A; Havekes, Louis M; Voshol, Peter J

    2011-05-01

    Low-grade inflammation in different tissues, including activation of the nuclear factor κB pathway in liver, is involved in metabolic disorders such as type 2 diabetes and cardiovascular diseases (CVDs). In this study, we investigated the relation between chronic hepatocyte-specific overexpression of IkB kinase (IKK)-β and hypertriglyceridemia, an important risk factor for CVD, by evaluating whether activation of IKK-β only in the hepatocyte affects VLDL-triglyceride (TG) metabolism directly. Transgenic overexpression of constitutively active human IKK-β specifically in hepatocytes of hyperlipidemic APOE*3-Leiden mice clearly induced hypertriglyceridemia. Mechanistic in vivo studies revealed that the hypertriglyceridemia was caused by increased hepatic VLDL-TG production rather than a change in plasma VLDL-TG clearance. Studies in primary hepatocytes showed that IKK-β overexpression also enhances TG secretion in vitro, indicating a direct relation between IKK-β activation and TG production within the hepatocyte. Hepatic lipid analysis and hepatic gene expression analysis of pathways involved in lipid metabolism suggested that hepatocyte-specific IKK-β overexpression increases VLDL production not by increased steatosis or decreased FA oxidation, but most likely by carbohydrate-responsive element binding protein-mediated upregulation of Fas expression. These findings implicate that specific activation of inflammatory pathways exclusively within hepatocytes induces hypertriglyceridemia. Furthermore, we identify the hepatocytic IKK-β pathway as a possible target to treat hypertriglyceridemia.

  8. Short-term overexpression of DGAT1 or DGAT2 increases hepatic triglyceride but not VLDL triglyceride or apoB production

    NARCIS (Netherlands)

    Millar, John S.; Stone, Scot J.; Tietge, Uwe J. F.; Tow, Bryan; Billheimer, Jeffrey T.; Wong, Jinny S.; Hamilton, Robert L.; Farese, Robert V.; Rader, Daniel J.

    2006-01-01

    Increased triglyceride synthesis resulting from enhanced flux of fatty acids into liver is frequently associated with VLDL overproduction. This has led to the common belief that hepatic triglyceride synthesis can directly modulate VLDL production. We used adenoviral vectors containing either murine

  9. Lipoprotein lipase release from BFC-1 beta adipocytes. Effects of triglyceride-rich lipoproteins and lipolysis products.

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    Sasaki, A; Goldberg, I J

    1992-07-25

    Lipoprotein lipase (LPL), synthesized by adipocytes and myocytes, must be transported to the luminal endothelial cell surface where it then interacts with circulating lipoproteins. The first step in this extracellular LPL transport pathway is LPL release from the surface of LPL-synthesizing cells. Because hydrolysis of triglyceride (TG)-rich lipoproteins releases LPL from the apical surface of endothelial cells, we hypothesized that the same substances dissociate LPL from adipocytes. 125I-LPL was bound to the surface of brown adipocytes (BFC-1 beta). LPL binding to the adipocyte surface was greater than to endothelial cell surfaces. Using low concentrations of heparin, more LPL was released from endothelial cells than BFC-1 beta, suggesting that the affinity of LPL binding to the adipocytes was greater than LPL affinity for endothelial cells. Greater than 3-fold more LPL was released from the cell surface when very low density lipoproteins (VLDL) were added to culture medium containing 3% bovine serum albumin. LPL remaining on the cell surface decreased with VLDL addition. Endogenously produced LPL activity was also released from the cells by VLDL. Low and high density lipoproteins did not release 125I-LPL or LPL activity from the adipocytes. To assess whether lipolysis was necessary for LPL release, BFC-1 beta were incubated with TG-rich lipoproteins from a patient with apoCII deficiency. The apoCII-deficient lipoproteins did not release LPL unless an exogenous source of apoCII was added. Apolipoproteins E and Cs and high molar ratios of oleic acid:bovine serum albumin did not release surface-associated LPL. Lysolecithin (25 and 100 microM), but not lecithin, monoglycerides, or diglycerides, released adipocyte surface LPL. Because lysolecithin also released LPL during a 4 degrees C incubation, cellular metabolic functions are not required for LPL dissociation from the cells. Lysolecithin also inhibited LPL binding to endothelial cells; however, this effect was

  10. GLP-1 receptor activation inhibits VLDL production and reverses hepatic steatosis by decreasing hepatic lipogenesis in high-fat-fed APOE*3-Leiden mice.

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    Edwin T Parlevliet

    Full Text Available OBJECTIVE: In addition to improve glucose intolerance, recent studies suggest that glucagon-like peptide-1 (GLP-1 receptor agonism also decreases triglyceride (TG levels. The aim of this study was to evaluate the effect of GLP-1 receptor agonism on very-low-density lipoprotein (VLDL-TG production and liver TG metabolism. EXPERIMENTAL APPROACH: The GLP-1 peptide analogues CNTO3649 and exendin-4 were continuously administered subcutaneously to high fat diet-fed APOE*3-Leiden transgenic mice. After 4 weeks, hepatic VLDL production, lipid content, and expression profiles of selected genes involved in lipid metabolism were determined. RESULTS: CNTO3649 and exendin-4 reduced fasting plasma glucose (up to -30% and -28% respectively and insulin (-43% and -65% respectively. In addition, these agents reduced VLDL-TG production (-36% and -54% respectively and VLDL-apoB production (-36% and -43% respectively, indicating reduced production of VLDL particles rather than reduced lipidation of apoB. Moreover, they markedly decreased hepatic content of TG (-39% and -55% respectively, cholesterol (-30% and -55% respectively, and phospholipids (-23% and -36% respectively, accompanied by down-regulation of expression of genes involved in hepatic lipogenesis (Srebp-1c, Fasn, Dgat1 and apoB synthesis (Apob. CONCLUSION: GLP-1 receptor agonism reduces VLDL production and hepatic steatosis in addition to an improvement of glycemic control. These data suggest that GLP-receptor agonists could reduce hepatic steatosis and ameliorate dyslipidemia in patients with type 2 diabetes mellitus.

  11. Acute central neuropeptide Y administration increases food intake but does not affect hepatic very low-density lipoprotein (VLDL production in mice.

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    Janine J Geerling

    Full Text Available OBJECTIVE: Central neuropeptide Y (NPY administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL-triglyceride (TG in rats. As hypertriglyceridemia is an important risk factor for atherosclerosis, for which well-established mouse models are available, we set out to validate the effect of NPY on hepatic VLDL-TG production in mice, to ultimately investigate whether NPY, by increasing VLDL production, contributes to the development of atherosclerosis. RESEARCH DESIGN AND METHODS: Male C57Bl/6J mice received an intracerebroventricular (i.c.v. cannula into the lateral (LV or third (3V ventricle of the brain. One week later, after a 4 h fast, the animals received an intravenous (i.v. injection of Tran(35S (100 µCi followed by tyloxapol (500 mg/kg body weight; BW, enabling the study of hepatic VLDL-apoB and VLDL-TG production, respectively. Immediately after the i.v. injection of tyloxapol, the animals received either an i.c.v. injection of NPY (0.2 mg/kg BW in artificial cerebrospinal fluid; aCSF, synthetic Y1 receptor antagonist GR231118 (0.5 mg/kg BW in aCSF or vehicle (aCSF, or an i.v. injection of PYY3-36 (0.5 mg/kg BW in PBS or vehicle (PBS. RESULTS: Administration of NPY into both the LV and 3V increased food intake within one hour after injection (+164%, p<0.001 and +367%, p<0.001, respectively. NPY administration neither in the LV nor in the 3V affected hepatic VLDL-TG or VLDL-apoB production. Likewise, antagonizing central NPY signaling by either PYY3-36 or GR231118 administration did not affect hepatic VLDL production. CONCLUSION: In mice, as opposed to rats, acute central administration of NPY increases food intake without affecting hepatic VLDL production. These results are of great significance when extrapolating findings on the central regulation of hepatic VLDL production between species.

  12. Hepatic VLDL production in ob/ob mice is not stimulated by massive de novo lipogenesis but is less sensitive to the suppressive effects of insulin.

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    Wiegman, Coen H; Bandsma, Robert H J; Ouwens, Margriet; van der Sluijs, Fjodor H; Havinga, Rick; Boer, Theo; Reijngoud, Dirk-Jan; Romijn, Johannes A; Kuipers, Folkert

    2003-05-01

    Type 2 diabetes in humans is associated with increased de novo lipogenesis (DNL), increased fatty acid (FA) fluxes, decreased FA oxidation, and hepatic steatosis. In this condition, VLDL production is increased and resistant to suppressive effects of insulin. The relationships between hepatic FA metabolism, steatosis, and VLDL production are incompletely understood. We investigated VLDL-triglyceride and -apolipoprotein (apo)-B production in relation to DNL and insulin sensitivity in female ob/ob mice. Hepatic triglyceride (5-fold) and cholesteryl ester (15-fold) contents were increased in ob/ob mice compared with lean controls. Hepatic DNL was increased approximately 10-fold in ob/ob mice, whereas hepatic cholesterol synthesis was not affected. Basal rates of hepatic VLDL-triglyceride and -apoB100 production were similar between the groups. Hyperinsulinemic clamping reduced VLDL-triglyceride and -apoB100 production rates by approximately 60% and approximately 75%, respectively, in lean mice but only by approximately 20% and approximately 20%, respectively, in ob/ob mice. No differences in hepatic expression of genes encoding apoB and microsomal triglyceride transfer protein were found. Hepatic expression and protein phosphorylation of insulin receptor and insulin receptor substrate isoforms were reduced in ob/ob mice. Thus, strongly induced hepatic DNL is not associated with increased VLDL production in ob/ob mice, possibly related to differential hepatic zonation of apoB synthesis (periportal) and lipid accumulation (perivenous) and/or relatively low rates of cholesterogenesis. Insulin is unable to effectively suppress VLDL-triglyceride production in ob/ob mice, presumably because of impaired insulin signaling.

  13. Adipocyte lipolysis-stimulated interleukin-6 production requires sphingosine kinase 1 activity.

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    Zhang, Wenliang; Mottillo, Emilio P; Zhao, Jiawei; Gartung, Allison; VanHecke, Garrett C; Lee, Jen-Fu; Maddipati, Krishna R; Xu, Haiyan; Ahn, Young-Hoon; Proia, Richard L; Granneman, James G; Lee, Menq-Jer

    2014-11-14

    Adipocyte lipolysis can increase the production of inflammatory cytokines such as interleukin-6 (IL-6) that promote insulin resistance. However, the mechanisms that link lipolysis with inflammation remain elusive. Acute activation of β3-adrenergic receptors (ADRB3) triggers lipolysis and up-regulates production of IL-6 in adipocytes, and both of these effects are blocked by pharmacological inhibition of hormone-sensitive lipase. We report that stimulation of ADRB3 induces expression of sphingosine kinase 1 (SphK1) and increases sphingosine 1-phosphate production in adipocytes in a manner that also depends on hormone-sensitive lipase activity. Mechanistically, we found that adipose lipolysis-induced SphK1 up-regulation is mediated by the c-Jun N-terminal kinase (JNK)/activating protein-1 signaling pathway. Inhibition of SphK1 by sphingosine kinase inhibitor 2 diminished the ADRB3-induced IL-6 production both in vitro and in vivo. Induction of IL-6 by ADRB3 activation was suppressed by siRNA knockdown of Sphk1 in cultured adipocytes and was severely attenuated in Sphk1 null mice. Conversely, ectopic expression of SphK1 increased IL-6 expression in adipocytes. Collectively, these data demonstrate that SphK1 is a critical mediator in lipolysis-triggered inflammation in adipocytes. © 2014 by The American Society for Biochemistry and Molecular Biology, Inc.

  14. Acute Central Neuropeptide Y Administration Increases Food Intake but Does Not Affect Hepatic Very Low-Density Lipoprotein (Vldl) Production in Mice

    NARCIS (Netherlands)

    Geerling, J.J.; Wang, Y.; Havekes, L.M.; Romijn, J.A.; Rensen, P.C.N.

    2013-01-01

    Objective: Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for athe

  15. Hepatic VLDL production in ob/ob mice is not stimulated by massive de novo lipogenesis but is less sensitive to the suppressive effects of insulin

    NARCIS (Netherlands)

    Wiegman, CH; Bandsma, RHJ; Ouwens, M; van der Sluijs, FH; Havinga, R; Boer, T; Reijngoud, DJ; Romijn, JA; Kuipers, F

    Type 2 diabetes in humans is associated with increased de novo lipogenesis (DNL), increased fatty acid (FA) fluxes, decreased FA oxidation, and hepatic steatosis. In this condition, VLDL production is increased and resistant to suppressive effects of insulin. The relationships between hepatic FA

  16. The coffee diterpene cafestol increases plasma triacylglycerol by increasing the production rate of large VLDL apolipoprotein B in healthy normolipidemic subjects

    NARCIS (Netherlands)

    Roos, de B.; Caslake, M.J.; Stalenhoef, A.F.H.; Bedford, D.; Demacker, P.N.; Katan, M.B.; Packard, C.J.

    2001-01-01

    Background: Cafestol is a diterpene in unfiltered coffee that raises plasma triacylglycerol in humans. Objective: We studied whether cafestol increases plasma triacylglycerol by increasing the production rate or by decreasing the fractional catabolic rate of VLDL1 [Svedberg flotation unit (Sf) 60-40

  17. Intracerebroventricular neuropeptide Y infusion precludes inhibition of glucose and VLDL production by insulin.

    NARCIS (Netherlands)

    Hoek, A.M. van den; Voshol, P.J.; Karnekamp, B.N.; Buijs, R.M.; Romijn, J.A.; Havekes, L.M.; Pijl, H.

    2004-01-01

    Recent evidence demonstrates that hypothalamic insulin signaling is required for inhibition of endogenous glucose production. The downstream mechanisms that are responsible for the effects of hypothalamic insulin receptor activation on hepatic fuel flux remain to be determined. To establish whether

  18. Measurement of lipolysis.

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    Schweiger, Martina; Eichmann, Thomas O; Taschler, Ulrike; Zimmermann, Robert; Zechner, Rudolf; Lass, Achim

    2014-01-01

    Lipolysis is defined as the hydrolytic cleavage of ester bonds in triglycerides (TGs), resulting in the generation of fatty acids (FAs) and glycerol. The two major TG pools in the body of vertebrates comprise intracellular TGs and plasma/nutritional TGs. Accordingly, this leads to the discrimination between intracellular and intravascular/gastrointestinal lipolysis, respectively. This chapter focuses exclusively on intracellular lipolysis, referred to as lipolysis herein. The lipolytic cleavage of TGs occurs in essentially all cells and tissues of the body. In all of them, the resulting FAs are utilized endogenously for energy production or biosynthetic pathways with one exception, white adipose tissue (WAT). WAT releases FAs and glycerol to supply nonadipose tissues at times of nutrient deprivation. The fundamental role of lipolysis in lipid and energy homeostasis requires the accurate measurement of lipase activities and lipolytic rates. The recent discovery of new enzymes and regulators that mediate the hydrolysis of TG has made these measurements more complex. Here, we describe detailed methodology for how to measure lipolysis and specific enzymes' activities in cells, organs, and their respective extracts. © 2014 Elsevier Inc. All rights reserved.

  19. LXR agonist increases apoE secretion from HepG2 spheroid, together with an increased production of VLDL and apoE-rich large HDL

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    Koike Kazuhiko

    2011-08-01

    Full Text Available Abstract Background The physiological regulation of hepatic apoE gene has not been clarified, although the expression of apoE in adipocytes and macrophages has been known to be regulated by LXR. Methods and Results We investigated the effect of TO901317, a LXR agonist, on hepatic apoE production utilizing HepG2 cells cultured in spheroid form, known to be more differentiated than HepG2 cells in monolayer culture. Spheroid HepG2 cells were prepared in alginate-beads. The secretions of albumin, apoE and apoA-I from spheroid HepG2 cells were significantly increased compared to those from monolayer HepG2 cells, and these increases were accompanied by increased mRNA levels of apoE and apoA-I. Several nuclear receptors including LXRα also became abundant in nuclear fractions in spheroid HepG2 cells. Treatment with TO901317 significantly increased apoE protein secretion from spheroid HepG2 cells, which was also associated with the increased expression of apoE mRNA. Separation of the media with FPLC revealed that the production of apoE-rich large HDL particles were enhanced even at low concentration of TO901317, and at higher concentration of TO901317, production of VLDL particles increased as well. Conclusions LXR activation enhanced the expression of hepatic apoE, together with the alteration of lipoprotein particles produced from the differentiated hepatocyte-derived cells. HepG2 spheroids might serve as a good model of well-differentiated human hepatocytes for future investigations of hepatic lipid metabolism.

  20. The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas.

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    Wiggins, D; Gibbons, G F

    1992-01-01

    In hepatocyte cultures maintained in the absence of extracellular fatty acids, at least 70% of the secreted very-low-density lipoprotein (VLDL) triacylglycerol was derived via lipolysis of intracellular triacylglycerol. This proportion was unchanged when the cells were exposed for 24 h to insulin or glucagon, hormones which decreased the overall secretion of intracellular triacylglycerol, or to chloroquine or tolbutamide, agents which inhibit lysosomal lipolysis. The rate of intracellular lipolysis was 2-3-fold greater than that required to maintain the observed rate of triacylglycerol secretion. Most of the fatty acids released were returned to the intracellular pool. Neither insulin nor glucagon had any significant effect on the overall lipolysis and re-esterification of intracellular triacylglycerol. In these cases a greater proportion of the released fatty acids re-entered the cellular pool, rather than being recruited for VLDL assembly. Tolbutamide inhibited intracellular lipolysis, but suppressed VLDL secretion to a greater extent. 3,5-Dimethylpyrazole did not affect lipolysis or VLDL secretion. The increased secretion of VLDL triacylglycerol observed after exposure of cells to insulin for 3 days was not accompanied by an increased rate of intracellular lipolysis. However, a larger proportion of the triacylglycerol secreted under these conditions may not have undergone prior lipolysis. PMID:1599431

  1. Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion

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    Wolfe, R.R.; Shaw, J.H.; Durkot, M.J.

    1985-06-01

    The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with (2-/sup 3/H)glycerol and (1-/sup 14/C)palmitic acid, was used to trace VLDL kinetics and oxidation, and (1-/sup 13/C)palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. The authors conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.

  2. Up-regulation of VLDL Receptor Expression and Its Signaling Pathway Induced by VLDL and β-VLDL

    Institute of Scientific and Technical Information of China (English)

    Zhiguo LIU; He LI; Yinghong LI; Yan WANG; Yiqiang ZONG; Youmei FENG; Zongchen FENG; Yaozu DENG; Shen QU

    2009-01-01

    Very low density lipoprotein receptor (VLDLR) is thought to participate in the patho-genesis of atherosclerosis induced by VLDL and β-VLDL. The present study was undertaken to elu-cidate the effects of VLDL and β-VLDL on VLDLR expression and its signaling pathway. RAW264.7 cells were incubated with VLDL and β-VLDL. The expression of VLDLR mRNA was detected by RT-PCR. The transcriptional activity of VLDLR gene was detected in recombinant plasmid pGL4.2VR-luciferase transfected RAW264.7. Western blot assay was used to detect the changes of phosphorylated ERK1/2 protein. Inhibitors or activators were used to observe the signal pathway in-volving VLDLR expression regulation. The results showed that VLDL and β-VLDL stimulated ERKI/2 activity in a PKC-dependent manner. VLDL or β-VLDL-induced VLDLR expression on macrophages was extremely abolished by inhibitors ERKI/2 or PKC. Our findings revealed that VLDL or β-VLDL-induced VLDLR expression via PKC/ERK cascades and the effect was linked to the transcriptional activation of VLDLR gene promoter.

  3. [Lipolysis lasers].

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    Mazer, J-M

    2009-10-01

    We use lipolysis lasers for around five years. The principle of those lasers is that, for some wavelengths, the fat, located in the adipocytes reacts as a chromophor. In order to allow the direct exposure of the adipocytes to the optical fiber (around 1mm diameter), this has to be inserted in the hypodermis, then move back and forth inside the treated areas. The theorical benefits, compared to the liposuction procedures are related to the fact that the thermal effect of the laser emission allows to avoid laxity, sometimes observed after a liposuction. If we consider the first publications related to this emerging procedure, the profile of tolerance seems good, and even possibly better than the liposuctions. Nevertheless, this procedure with lasers is still a surgical procedure, exposing theorically to the side effects related in and after each surgery: infections, ecchymosis... Recently, some cases of severe side effects (infection of the skin, and necrosis) have been reported. They seem to be related to a homogeneous distribution of the energy inducing an excessive thermal injury. Some new improvements, with the last generation lasers, could allow us to avoid, or at least to dramatically reduce those side effects. The efficacy of those lasers is visibly satisfying; the key question is to precise the optimal modalities of use : in a surgery room, after an optimal training, with the last generation lasers?

  4. A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions.

    Science.gov (United States)

    Adiels, Martin; Packard, Chris; Caslake, Muriel J; Stewart, Philip; Soro, Aino; Westerbacka, Jukka; Wennberg, Bernt; Olofsson, Sven-Olof; Taskinen, Marja-Riitta; Borén, Jan

    2005-01-01

    The use of stable isotopes in conjunction with compartmental modeling analysis has greatly facilitated studies of the metabolism of the apolipoprotein B (apoB)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2) after a bolus injection of [(2)H(3)]leucine and [(2)H(5)]glycerol and to follow the catabolism and transfer of the lipoprotein particles. Here, we describe the model and present the results of its application in a fasting steady-state situation in 17 subjects with lipid values representative of a Western population. Analysis of the correlations showed that plasma TG was determined by the VLDL(1) and VLDL(2) apoB and TG fractional catabolic rate. Furthermore, the model showed a linear correlation between VLDL(1) TG and apoB production. A novel observation was that VLDL TG entered the circulation within 21 min after its synthesis, whereas VLDL apoB entered the circulation after 33 min. These observations are consistent with a sequential assembly model of VLDL and suggest that the TG is added to a primordial apoB-containing particle in the liver.

  5. Effect of apolipoprotein E variants on lipolysis of very low density lipoproteins by heparan sulphate proteoglycan-bound lipoprotein lipase

    NARCIS (Netherlands)

    Man, F.H.A.F. de; Beer, F. de; Laarse, A. van der; Smelt, A.H.M.; Leuven, J.A.G.; Havekes, L.M.

    1998-01-01

    Lipoprotein lipase (LPL) is bound to heparan sulphate proteoglycans (HSPG) at the luminal surface of endothelium. It is the key enzyme involved in the hydrolysis of very low density lipoproteins (VLDL). Prior to lipolysis by LPL, the lipoproteins are considered to interact with vessel wall HSPG. Apo

  6. Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver.

    Science.gov (United States)

    Fu, Jihua; Ma, Shaoxin; Li, Xin; An, Shanshan; Li, Tao; Guo, Keke; Lin, Min; Qu, Wei; Wang, Shanshan; Dong, Xinyue; Han, Xiaoyu; Fu, Ting; Huang, Xinping; Wang, Tianying; He, Siyu

    2016-01-01

    Hepatic triglycerides production and adipose lipolysis are pivotal for long-term stress (LTS) or hyperglucocorticoidemia-induced insulin resistance. 5-hydroxytryptamine (5-HT) has been demonstrated to induce hepatic lipid metabolic abnormality by activating mammalian target of rapamycin (mTOR). In present study, we explored whether 5-HT is involved in LTS effects in liver using restraint stress-exposed rats and cultured primary rat hepatocytes and HepG2 cells. LTS with hyperglucocorticoidemia induced hepatic 5-HT synthetic increase with tryptophan hydroxylase 1 (Tph1) up-regulation, and 5-HT2 receptor (5-HT2R, including 5-HT2A, 2B receptor) up-regulation in liver and visceral adipose, as well as hepatic mTOR activation with triglycerides and VLDL overproduction with steatosis, and visceral adipose lipolytic increase with high blood free fatty acids (FFAs) level. 5-HT exposure exhibited LTS-like effects in both tissues, and both LTS and 5-HT effects could be abolished significantly by blocking 5-HT2R. In HepG2 cells dexamethasone or palmitate-induced mTOR activation with triglycerides and VLDL overproduction were accompanied by up-regulations of 5-HT synthesis and 5-HT2R, which were significantly abolished by gene silencing Tph1 or 5-HT2R and were almost fully abolished by co-silencing of both, especially on VLDL overproduction. Chemical inhibition of Tph1 or/and 5-HT2R in both hepatocytes exhibited similar abolishment with genetic inhibition on dexamethason-induced effects. 5-HT-stimulated effects in both hepatocytes were fully abolished by blocking 5-HT2R, while 5-HT itself also up-regulated 5-HT2R. In conclusion, up-regulated hepatic 5-HT synthesis and 5-HT2R induced by both glucocorticoid and FFAs are crucial for LTS-induced hepatic steatosis with VLDL overproduction, while 5-HT by acting on 5-HT2R mediates mTOR activation in liver.

  7. Preparation and Characterization of Polyclonal Antibodies against VLDL Receptor

    Institute of Scientific and Technical Information of China (English)

    屈伸; 陈涛; 吴凡; 尹燕华; 毕昊

    2004-01-01

    Summary: The polyclonal antibodies against VLDL receptor were prepared and identified. Rabbits were immunized with polypeptide fragment of VLDL receptor as antigen. The collected blood serum of the immunized rabbits was analyzed and identified by using ELISA and Western Blot. The results showed that the rabbit against mouse and human VLDL receptor antibodies were obtained with high titer and could recognize the natural VLDL receptors through Western blot. The prepared poly clonal antibodies against VLDL receptor provide a new tool to study the protein of VLDL receptor.

  8. Adipose tissue lipolysis.

    Science.gov (United States)

    Kolditz, Catherine-Ines; Langin, Dominique

    2010-07-01

    Adipose tissue lipolysis is a critical pathway for the maintenance of energy homeostasis through the degradation of triglycerides and the release of fatty acids into the circulation. The understanding of the cellular factors regulating triglyceride hydrolysis and the metabolic function of lipases has considerably expanded in the last few years, revealing an unexpected complexity. This review aims at describing recent discoveries related to the lipolytic pathway and its regulatory mechanisms. Considerable progress has been made in understanding the role and the mechanisms of activation of the lipolytic enzymes. Recent discoveries have dramatically altered the view of adipose tissue lipolysis and highlighted the importance of additional molecular actors in regulating this process. Catecholamines, natriuretic peptides, and insulin are considered to be the major regulators of lipolysis in humans. However, autocrine/paracrine factors such as metabolites and prostaglandins may also participate in its regulation. The manipulation of lipolysis has therapeutic potential in the metabolic disorders frequently associated with obesity. Unraveling the molecular events occurring during regulation of lipolysis may lead to novel therapeutic targets.

  9. Lipolysis and lipases in white adipose tissue - An update.

    Science.gov (United States)

    Bolsoni-Lopes, Andressa; Alonso-Vale, Maria Isabel C

    2015-08-01

    Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanisms involved, which reformulated the concept of lipolysis. Novel findings from these studies include the identification of lipolytic products as signaling molecules regulating important metabolic processes in many non-adipose tissues, unveiling a previously underestimated aspect of lipolysis. Thus, we present here an updated review of concepts and regulation of white adipocyte lipolysis with a special emphasis in its role in metabolism homeostasis and as a source of important signaling molecules.

  10. Intracellular & extracellular lipolysis

    NARCIS (Netherlands)

    Dijk, Wieneke

    2016-01-01

    The body efficiently stores energy in the form of triglyceride (fat) molecules. However, triglycerides cannot directly enter or exit our cells, but first need to be degraded to so-called fatty acids before moving in or out a cell. This degradation process, called lipolysis, is crucial for human phys

  11. Overproduction of altered VLDL in an insulin-resistance rat model: Influence of SREBP-1c and PPAR-α.

    Science.gov (United States)

    Lucero, Diego; Miksztowicz, Verónica; Macri, Vanesa; López, Gustavo H; Friedman, Silvia; Berg, Gabriela; Zago, Valeria; Schreier, Laura

    2015-01-01

    In insulin-resistance, VLDL presents alterations that increase its atherogenic potential. The mechanism by which insulin-resistance promotes the production of altered VLDL is still not completely understood. The aim of this study was to evaluate the relationship between the expression of sterol regulatory element binding protein 1c (SREBP-1c) and of peroxisome proliferator-activated receptor-α (PPAR-α), with the features of composition and size of VLDL in an insulin-resistance rat model induced by a sucrose rich diet (SRD). The study was conducted on 12 male Wistar rats (180g) receiving SRD (12 weeks) and 12 controls. Lipid profile, free fatty acids, glucose, and insulin were measured. Lipid content in liver and visceral fat were assessed. Isolated VLDL (d<1.006g/ml) was characterized by its chemical composition and size by HPLC. The respective hepatic expression of SREBP-1c and PPAR-α was determined (Western blot). As expected, SRD had elevated triglycerides (TG), free fatty acids and insulin levels, and decreased HDL-cholesterol (p<0.05), together with augmented hepatic and visceral fat (p<0.05). SRD showed higher VLDL total mass - with increased TG content - and predominance of large VLDL (p<0.05). SRD showed an increase in SREBP-1c (precursor and mature forms) and decreased PPAR-α expression (p<0.045). SREBP-1c forms were positively associated with VLDL total mass (p<0.04), VLDL-TG% (p<0.019), and large VLDL% (p<0.002). On the other hand, PPAR-α correlated negatively with VLDL total mass (p=0.05), VLDL-TG% (p=0.005), and large VLDL% (p=0.002). Insulin-resistance, by coordinated activation of SREBP-1c and reduction of PPAR-α, could promote the secretion of larger and TG over-enriched VLDL particles, with greater atherogenic capacity. Copyright © 2014 Sociedad Española de Arteriosclerosis. Published by Elsevier España. All rights reserved.

  12. Lipolysis in Skeletal Muscle

    DEFF Research Database (Denmark)

    Serup, Annette Karen Lundbeck

    and especially the energy sensor 5' adenosine monophosphate-activated protein kinase (AMPK), which is activated during exercise, has received increased attention. However, whether AMPK is an activator or inhibitor of lipolysis in skeletal muscle is not clear. Therefore, we in study I aimed to identify the role...... contraction. Accordingly, AMPK is suggested to be an important regulator of basal IMTG and lipid handling in skeletal muscle as well as an important activator of lipolysis by phosphorylation of ATGL and HSL during muscle contractions. Oversupply of energy and dietary fat leads to obesity and accumulation...... chemical structure of DAG. We took advantage of the fact that insulin sensitivity is increased after exercise, and that mice knocked out (KO) of HSL accumulate DAG after exercise, and measured insulin stimulated glucose uptake after treadmill running in skeletal muscle from HSL KO mice and wildtype control...

  13. Immobilised lipase for in vitro lipolysis experiments.

    Science.gov (United States)

    Phan, Stephanie; Salentinig, Stefan; Hawley, Adrian; Boyd, Ben J

    2015-04-01

    In vitro lipolysis experiments are used to assess digestion of lipid-based formulations, and probe solubilisation by colloidal phases during digestion. However, proteins and other biological components in the pancreatin often used as the lipase result in high-background scattering when interrogating structures using scattering approaches, complicating the resolution of colloidal structures. In this study, to circumvent this problem, a modified in vitro digestion model employing lipase immobilised on polymer beads, which allows for separation of the lipid digestion components during lipolysis, was investigated. Titration of the fatty acids released during digestion of medium chain triglycerides using pancreatin compared with immobilised lipase, combined with HPLC was used to follow the digestion, and small-angle X-ray scattering was used to determine colloidal structure formation. Digestion of medium chain triglycerides at the same nominal activity revealed that for the immobilised lipase, a longer digestion time was required to achieve the same extent of digestion. However, the same structural endpoint was observed, indicating that structure formation was not affected by the choice of lipase used. Lipolysis with immobilised lipase led to the reduction of parasitic scattering, resulting in clearer and more defined scattering from the structures generated by the lipolysis products. © 2015 Wiley Periodicals, Inc. and the American Pharmacists Association.

  14. Overproduction of a kinetic subclass of VLDL-apoB, and direct catabolism of VLDL-apoB in human endogenous hypertriglyceridemia: an analytical model solution of tracer data

    Energy Technology Data Exchange (ETDEWEB)

    Eaton, R.P.; Allen, R.C.; Schade, D.S.

    1983-10-01

    To investigate the participation of the major apoprotein involved in triglyceride transport in the pathogenesis of endogenous hypertriglyceridemia, five kinetic studies of apoprotein B were conducted in volunteer normolipidemic subjects and six studies in four patients with endogenous hypertriglyceridemia. The transport of apoprotein B within four kinetic subclasses of very low density lipoprotein (VLDL), intermediate density lipoprotein (IDL), and low density lipoprotein (LDL) was studied by injection of (/sup 75/Se)selenomethionine. A 24-fold increase in the entry of newly synthesized apoprotein B at the initial kinetic subclass of the four-compartment VLDL delipidation sequence characterized the hypertriglyceridemic studies relative to normal subjects. Moreover, approximately 75 mg/kg per day of VLDL-B turnover reflected direct catabolism independent of conversion to IDL and/or to LDL, in contrast to the 8 mg/kg per day observed in controls. IDL-B was derived from VLDL-B in both normal and hypertriglyceridemic subjects, and was responsible for greater than 70% of all LDL-B synthesis. LDL-B pool size and turnover were indistinguishable in hypertriglyceridemic subjects from that observed in normal subjects. These studies suggest that two kinetic phenomena may characterize the pathophysiology of endogenous hypertriglyceridemia: a) over-production of apoB within a kinetic subclass of VLDL and b) preferential catabolism of hypertriglyceridemic VLDL without prior conversion to IDL/LDL.

  15. Influence of milk quality and production protocol on proteolysis and lipolysis in Monti Dauni Meridionali Caciocavallo cheese.

    Science.gov (United States)

    Albenzio, Marzia; Santillo, Antonella; Russo, Donatella Esterina; Caroprese, Mariangela; Marino, Rosaria; Sevi, Agostino

    2010-11-01

    The aim of this study was to assess the effect of milk source and of cheese production protocol on proteolytic and lipolytic pattern of cheese during ripening. The study involved six dairy factories located in Monti Dauni Meridionali area of Southern Italy; three dairy factories processed the milk produced by their own cow herds, while the other three dairy factories processed the milk collected in other dairy farms located in the neighbouring area. Cow milk processed to cheese had different nutritional parameters and hygienic quality. Caciocavallo cheese showed differences in the evolution of proteolysis during ripening and in the intensity of the lipolytic process detected at the end of ripening. The main factors influencing Caciocavallo cheese features were the quality of the starting milk, differences in technological steps such as milk heating, type of starter cultures and coagulant used.

  16. VLDL hydrolysis by hepatic lipase regulates PPARδ transcriptional responses.

    Directory of Open Access Journals (Sweden)

    Jonathan D Brown

    Full Text Available BACKGROUND: PPARs (α,γ,δ are a family of ligand-activated transcription factors that regulate energy balance, including lipid metabolism. Despite these critical functions, the integration between specific pathways of lipid metabolism and distinct PPAR responses remains obscure. Previous work has revealed that lipolytic pathways can activate PPARs. Whether hepatic lipase (HL, an enzyme that regulates VLDL and HDL catabolism, participates in PPAR responses is unknown. METHODS/PRINCIPAL FINDINGS: Using PPAR ligand binding domain transactivation assays, we found that HL interacted with triglyceride-rich VLDL (>HDL≫LDL, IDL to activate PPARδ preferentially over PPARα or PPARγ, an effect dependent on HL catalytic activity. In cell free ligand displacement assays, VLDL hydrolysis by HL activated PPARδ in a VLDL-concentration dependent manner. Extended further, VLDL stimulation of HL-expressing HUVECs and FAO hepatoma cells increased mRNA expression of canonical PPARδ target genes, including adipocyte differentiation related protein (ADRP, angiopoietin like protein 4 and pyruvate dehydrogenase kinase-4. HL/VLDL regulated ADRP through a PPRE in the promoter region of this gene. In vivo, adenoviral-mediated hepatic HL expression in C57BL/6 mice increased hepatic ADRP mRNA levels by 30%. In ob/ob mice, a model with higher triglycerides than C57BL/6 mice, HL overexpression increased ADRP expression by 70%, demonstrating the importance of triglyceride substrate for HL-mediated PPARδ activation. Global metabolite profiling identified HL/VLDL released fatty acids including oleic acid and palmitoleic acid that were capable of recapitulating PPARδ activation and ADRP gene regulation in vitro. CONCLUSIONS: These data define a novel pathway involving HL hydrolysis of VLDL that activates PPARδ through generation of specific monounsaturated fatty acids. These data also demonstrate how integrating cell biology with metabolomic approaches provides insight

  17. Adipocyte lipolysis and insulin resistance.

    Science.gov (United States)

    Morigny, Pauline; Houssier, Marianne; Mouisel, Etienne; Langin, Dominique

    2016-06-01

    Obesity-induced insulin resistance is a major risk factor for the development of type 2 diabetes. Basal fat cell lipolysis (i.e., fat cell triacylglycerol breakdown into fatty acids and glycerol in the absence of stimulatory factors) is elevated during obesity and is closely associated with insulin resistance. Inhibition of adipocyte lipolysis may therefore be a promising therapeutic strategy for treating insulin resistance and preventing obesity-associated type 2 diabetes. In this review, we explore the relationship between adipose lipolysis and insulin sensitivity. After providing an overview of the components of fat cell lipolytic machinery, we describe the hypotheses that may support the causality between lipolysis and insulin resistance. Excessive circulating fatty acids may ectopically accumulate in insulin-sensitive tissues and impair insulin action. Increased basal lipolysis may also modify the secretory profile of adipose tissue, influencing whole body insulin sensitivity. Finally, excessive fatty acid release may also worsen adipose tissue inflammation, a well-known parameter contributing to insulin resistance. Partial genetic or pharmacologic inhibition of fat cell lipases in mice as well as short term clinical trials using antilipolytic drugs in humans support the benefit of fat cell lipolysis inhibition on systemic insulin sensitivity and glucose metabolism, which occurs without an increase of fat mass. Modulation of fatty acid fluxes and, putatively, of fat cell secretory pattern may explain the amelioration of insulin sensitivity whereas changes in adipose tissue immune response do not seem involved. Copyright © 2015 Elsevier B.V. and Société Française de Biochimie et Biologie Moléculaire (SFBBM). All rights reserved.

  18. Control of lipolysis by natriuretic peptides and cyclic GMP.

    Science.gov (United States)

    Lafontan, Max; Moro, Cédric; Berlan, Michel; Crampes, François; Sengenes, Coralie; Galitzky, Jean

    2008-01-01

    Human fat cell lipolysis was, until recently, thought to be mediated exclusively by a cAMP-dependent protein kinase (PKA)-regulated pathway under the control of catecholamines and insulin. We have shown that atrial- and B-type natriuretic peptides (ANP and BNP respectively) stimulate lipolysis in human fat cells through a cGMP-dependent protein kinase (PKG) signaling pathway independent of cAMP production and PKA activity. Pharmacological or physiological (exercise) increases in plasma ANP levels stimulate lipid mobilization in humans. This pathway becomes important during chronic treatment with beta-adrenoceptor antagonists, which inhibit catecholamine-induced lipolysis but enhance cardiac ANP release. These findings have metabolic implications and point to potential problems when natriuretic peptide secretion is altered or during therapeutic use of recombinant BNP.

  19. Lipolysis Response to Endoplasmic Reticulum Stress in Adipose Cells*

    Science.gov (United States)

    Deng, Jingna; Liu, Shangxin; Zou, Liangqiang; Xu, Chong; Geng, Bin; Xu, Guoheng

    2012-01-01

    In obesity and diabetes, adipocytes show significant endoplasmic reticulum (ER) stress, which triggers a series of responses. This study aimed to investigate the lipolysis response to ER stress in rat adipocytes. Thapsigargin, tunicamycin, and brefeldin A, which induce ER stress through different pathways, efficiently activated a time-dependent lipolytic reaction. The lipolytic effect of ER stress occurred with elevated cAMP production and protein kinase A (PKA) activity. Inhibition of PKA reduced PKA phosphosubstrates and attenuated the lipolysis. Although both ERK1/2 and JNK are activated during ER stress, lipolysis is partially suppressed by inhibiting ERK1/2 but not JNK and p38 MAPK and PKC. Thus, ER stress induces lipolysis by activating cAMP/PKA and ERK1/2. In the downstream lipolytic cascade, phosphorylation of lipid droplet-associated protein perilipin was significantly promoted during ER stress but attenuated on PKA inhibition. Furthermore, ER stress stimuli did not alter the levels of hormone-sensitive lipase and adipose triglyceride lipase but caused Ser-563 and Ser-660 phosphorylation of hormone-sensitive lipase and moderately elevated its translocation from the cytosol to lipid droplets. Accompanying these changes, total activity of cellular lipases was promoted to confer the lipolysis. These findings suggest a novel pathway of the lipolysis response to ER stress in adipocytes. This lipolytic activation may be an adaptive response that regulates energy homeostasis but with sustained ER stress challenge could contribute to lipotoxicity, dyslipidemia, and insulin resistance because of persistently accelerated free fatty acid efflux from adipocytes to the bloodstream and other tissues. PMID:22223650

  20. Lipolysis response to endoplasmic reticulum stress in adipose cells.

    Science.gov (United States)

    Deng, Jingna; Liu, Shangxin; Zou, Liangqiang; Xu, Chong; Geng, Bin; Xu, Guoheng

    2012-02-24

    In obesity and diabetes, adipocytes show significant endoplasmic reticulum (ER) stress, which triggers a series of responses. This study aimed to investigate the lipolysis response to ER stress in rat adipocytes. Thapsigargin, tunicamycin, and brefeldin A, which induce ER stress through different pathways, efficiently activated a time-dependent lipolytic reaction. The lipolytic effect of ER stress occurred with elevated cAMP production and protein kinase A (PKA) activity. Inhibition of PKA reduced PKA phosphosubstrates and attenuated the lipolysis. Although both ERK1/2 and JNK are activated during ER stress, lipolysis is partially suppressed by inhibiting ERK1/2 but not JNK and p38 MAPK and PKC. Thus, ER stress induces lipolysis by activating cAMP/PKA and ERK1/2. In the downstream lipolytic cascade, phosphorylation of lipid droplet-associated protein perilipin was significantly promoted during ER stress but attenuated on PKA inhibition. Furthermore, ER stress stimuli did not alter the levels of hormone-sensitive lipase and adipose triglyceride lipase but caused Ser-563 and Ser-660 phosphorylation of hormone-sensitive lipase and moderately elevated its translocation from the cytosol to lipid droplets. Accompanying these changes, total activity of cellular lipases was promoted to confer the lipolysis. These findings suggest a novel pathway of the lipolysis response to ER stress in adipocytes. This lipolytic activation may be an adaptive response that regulates energy homeostasis but with sustained ER stress challenge could contribute to lipotoxicity, dyslipidemia, and insulin resistance because of persistently accelerated free fatty acid efflux from adipocytes to the bloodstream and other tissues.

  1. Splanchnic lipolysis in human obesity

    OpenAIRE

    Nielsen, Soren; Guo, ZengKui; Johnson, C. Michael; Hensrud, Donald D.; Jensen, Michael D

    2004-01-01

    Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obe...

  2. The effect of interaction between Lipoprotein Lipase and ApoVLDL-II ...

    African Journals Online (AJOL)

    The effect of interaction between Lipoprotein Lipase and ApoVLDL-II genes on fat and serum biochemical levels. ... Single nucleotide polymorphism (SNP) in apoVLDL-II and lipoprotein lipase genes was screened by ... Article Metrics.

  3. A new combined multicompartmental model for apolipoprotein B-100 and triglyceride metabolism in VLDL subfractions

    National Research Council Canada - National Science Library

    Adiels, Martin; Packard, Chris; Caslake, Muriel J; Stewart, Philip; Soro, Aino; Westerbacka, Jukka; Wennberg, Bernt; Olofsson, Sven-Olof; Taskinen, Marja-Riitta; Borén, Jan

    ...)-containing lipoproteins in humans. The aim of this study was to develop a multicompartment model that allows us to simultaneously determine the kinetics of apoB and triglyceride (TG) in VLDL(1) and VLDL(2...

  4. Splanchnic lipolysis in human obesity

    Science.gov (United States)

    Nielsen, Soren; Guo, ZengKui; Johnson, C. Michael; Hensrud, Donald D.; Jensen, Michael D.

    2004-01-01

    Elevated FFA concentrations have been shown to reproduce some of the metabolic abnormalities of obesity. It has been hypothesized that visceral adipose tissue lipolysis releases excess FFAs into the portal vein, exposing the liver to higher FFA concentrations. We used isotope dilution/hepatic vein catheterization techniques to examine whether intra-abdominal fat contributes a greater portion of hepatic FFA delivery in visceral obesity. Obese women (n = 24) and men (n = 20) with a range of obesity phenotypes, taken together with healthy, lean women (n = 12) and men (n = 12), were studied. Systemic, splanchnic, and leg FFA kinetics were measured. The results showed that plasma FFA concentrations were approximately 20% greater in obese men and obese women. The contribution of splanchnic lipolysis to hepatic FFA delivery ranged from less than 10% to almost 50% and increased as a function of visceral fat in women (r = 0.49, P = 0.002) and in men (r = 0.52, P = 0.002); the slope of the relationship was greater in women than in men (P < 0.05). Leg and splanchnic tissues contributed a greater portion of systemic FFA release in obese men and women than in lean men and women. We conclude that the contribution of visceral adipose tissue lipolysis to hepatic FFA delivery increases with increasing visceral fat in humans and that this effect is greater in women than in men. PMID:15173884

  5. Echium Oil Reduces Plasma Triglycerides by Increasing Intravascular Lipolysis in apoB100-Only Low Density Lipoprotein (LDL Receptor Knockout Mice

    Directory of Open Access Journals (Sweden)

    John S. Parks

    2013-07-01

    Full Text Available Echium oil (EO, which is enriched in SDA (18:4 n-3, reduces plasma triglyceride (TG concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%, EO (10% EO + 10% PO, or FO (10% FO + 10% PO. Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL particle size was ordered: PO (63 ± 4 nm > EO (55 ± 3 nm > FO (40 ± 2 nm. Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  6. Echium oil reduces plasma triglycerides by increasing intravascular lipolysis in apoB100-only low density lipoprotein (LDL) receptor knockout mice.

    Science.gov (United States)

    Forrest, Lolita M; Lough, Christopher M; Chung, Soonkyu; Boudyguina, Elena Y; Gebre, Abraham K; Smith, Thomas L; Colvin, Perry L; Parks, John S

    2013-07-12

    Echium oil (EO), which is enriched in SDA (18:4 n-3), reduces plasma triglyceride (TG) concentrations in humans and mice. We compared mechanisms by which EO and fish oil (FO) reduce plasma TG concentrations in mildly hypertriglyceridemic male apoB100-only LDLrKO mice. Mice were fed one of three atherogenic diets containing 0.2% cholesterol and palm oil (PO; 20%), EO (10% EO + 10% PO), or FO (10% FO + 10% PO). Livers from PO- and EO-fed mice had similar TG and cholesteryl ester (CE) content, which was significantly higher than in FO-fed mice. Plasma TG secretion was reduced in FO vs. EO-fed mice. Plasma very low density lipoprotein (VLDL) particle size was ordered: PO (63 ± 4 nm) > EO (55 ± 3 nm) > FO (40 ± 2 nm). Post-heparin lipolytic activity was similar among groups, but TG hydrolysis by purified lipoprotein lipase was significantly greater for EO and FO VLDL compared to PO VLDL. Removal of VLDL tracer from plasma was marginally faster in EO vs. PO fed mice. Our results suggest that EO reduces plasma TG primarily through increased intravascular lipolysis of TG and VLDL clearance. Finally, EO may substitute for FO to reduce plasma TG concentrations, but not hepatic steatosis in this mouse model.

  7. Mathematical modeling of laser lipolysis

    Directory of Open Access Journals (Sweden)

    Reynaud Jean

    2008-02-01

    Full Text Available Abstract Background and Objectives Liposuction continues to be one of the most popular procedures performed in cosmetic surgery. As the public's demand for body contouring continues, laser lipolysis has been proposed to improve results, minimize risk, optimize patient comfort, and reduce the recovery period. Mathematical modeling of laser lipolysis could provide a better understanding of the laser lipolysis process and could determine the optimal dosage as a function of fat volume to be removed. Study design/Materials and Methods An Optical-Thermal-Damage Model was formulated using finite-element modeling software (Femlab 3.1, Comsol Inc. The general model simulated light distribution using the diffusion approximation of the transport theory, temperature rise using the bioheat equation and laser-induced injury using the Arrhenius damage model. Biological tissue was represented by two homogenous regions (dermis and fat layer with a nonlinear air-tissue boundary condition including free convection. Video recordings were used to gain a better understanding of the back and forth movement of the cannula during laser lipolysis in order to consider them in our mathematical model. Infrared video recordings were also performed in order to compare the actual surface temperatures to our calculations. The reduction in fat volume was determined as a function of the total applied energy and subsequently compared to clinical data reported in the literature. Results In patients, when using cooled tumescent anesthesia, 1064 nm Nd:YAG laser or 980 nm diode laser: (6 W, back and forth motion: 100 mm/s give similar skin surface temperature (max: 41°C. These measurements are in accordance with those obtained by mathematical modeling performed with a 1 mm cannula inserted inside the hypodermis layer at 0.8 cm below the surface. Similarly, the fat volume reduction observed in patients at 6-month follow up can be determined by mathematical modeling. This fat reduction

  8. Impaired Insulin Suppression of VLDL-Triglyceride Kinetics in Non-alcoholic Fatty Liver Disease

    DEFF Research Database (Denmark)

    Poulsen, Marianne K; Nellemann, Birgitte; Stødkilde-Jørgensen, Hans;

    2016-01-01

    CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting and hyperin......CONTEXT: Non-alcoholic fatty liver disease (NAFLD) is associated with glucose and lipid metabolic abnormalities. However, insulin suppression of VLDL-triglyceride (VLDL-TG) kinetics is not fully understood. OBJECTIVE: To determine VLDL-TG, glucose and palmitate kinetics during fasting...... and hyperinsulinemia in men with (NAFLD+) and without NAFLD (NAFLD-). DESIGN: 27 non-diabetic, upper-body obese (WHR >0.9, BMI >28 kg/m(2)) men, 18 NAFLD+ and 9 NAFLD- determined by magnetic resonance spectroscopy, were enrolled.(14)C-labeled VLDL-TG and (3)H-labeled glucose and palmitate tracers were applied...... metabolic abnormalities associated with NAFLD and presumably diabetes....

  9. Catecholamine-induced lipolysis causes mTOR complex dissociation and inhibits glucose uptake in adipocytes.

    Science.gov (United States)

    Mullins, Garrett R; Wang, Lifu; Raje, Vidisha; Sherwood, Samantha G; Grande, Rebecca C; Boroda, Salome; Eaton, James M; Blancquaert, Sara; Roger, Pierre P; Leitinger, Norbert; Harris, Thurl E

    2014-12-09

    Anabolic and catabolic signaling oppose one another in adipose tissue to maintain cellular and organismal homeostasis, but these pathways are often dysregulated in metabolic disorders. Although it has long been established that stimulation of the β-adrenergic receptor inhibits insulin-stimulated glucose uptake in adipocytes, the mechanism has remained unclear. Here we report that β-adrenergic-mediated inhibition of glucose uptake requires lipolysis. We also show that lipolysis suppresses glucose uptake by inhibiting the mammalian target of rapamycin (mTOR) complexes 1 and 2 through complex dissociation. In addition, we show that products of lipolysis inhibit mTOR through complex dissociation in vitro. These findings reveal a previously unrecognized intracellular signaling mechanism whereby lipolysis blocks the phosphoinositide 3-kinase-Akt-mTOR pathway, resulting in decreased glucose uptake. This previously unidentified mechanism of mTOR regulation likely contributes to the development of insulin resistance.

  10. Apolipoprotein A-V Deficiency Results in MarkedHypertriglyceridemia Attributable to Decreased Lipolysis ofTriglyceride-Rich Lipoproteins and Removal of Their Remnants

    Energy Technology Data Exchange (ETDEWEB)

    Grosskopf, Itamar; Baroukh, Nadine; Lee, Sung-Joon; Kamari,Yehuda; Harats, Dror; Rubin, Edward M.; Pennacchio, Len A.; Cooper, AllenD.

    2005-09-01

    Objective--ApoAV, a newly discovered apoprotein, affectsplasma triglyceride level. To determine how this occurs, we studiedtriglyceride-rich lipoprotein (TRL) metabolism in mice deficient inapoAV. Methods and Results No significant difference in triglycerideproduction rate was found between apoa5_/_ mice and controls. Thepresence or absence of apoAV affected TRL catabolism. After the injectionof 14C-palmitate and 3H-cholesterol labeled chylomicrons and 125I-labeledchylomicron remnants, the disappearance of 14C, 3H, and 125I wassignificantly slower in apoa5_/_ mice relative to controls. This wasbecause of diminished lipolysis of TRL and the reduced rate of uptake oftheir remnants in apoa5_/_ mice. Observed elevated cholesterol level wascaused by increased high-density lipoprotein (HDL) cholesterol inapoa5_/_ mice. VLDL from apoa5_/_ mice were poor substrate forlipoprotein lipase, and did not bind to the low-density lipoprotein (LDL)receptor as well as normal very-low-density lipoprotein (VLDL). LDLreceptor levels were slightly elevated in apoa5_/_ mice consistent withlower remnant uptake rates. These alterations may be the result of thelower apoE-to-apoC ratio found in VLDL isolated from apoa5_/_mice.Conclusions These results support the hypothesis that the absence ofapoAV slows lipolysis of TRL and the removal of their remnants byregulating their apoproteins content after secretion.

  11. ApoB100-LDL acts as a metabolic signal from liver to peripheral fat causing inhibition of lipolysis in adipocytes.

    Directory of Open Access Journals (Sweden)

    Josefin Skogsberg

    Full Text Available BACKGROUND: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. METHODS AND FINDINGS: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr(-/-Apob(100/100. CONCLUSIONS: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome.

  12. Effect of Alternative Splicing of VLDL Receptor on its Ligand Binding and Internalization Capability

    Institute of Scientific and Technical Information of China (English)

    Ying-Hong LI; Jun TIAN; Tao CHEN; Yi-Qiang ZONG; Yu WANG; Pu YANG; Shen QU

    2005-01-01

    @@ 1 Introduction Very low density lipoprotein receptor (VLDL-R) is a main receptor mediating the uptake of triglyceride-rich lipoprotein(TRL), so it is in all probability to play an important role in the development of atherosclerosis(AS). On account of alternative splicing of O-linked carbohydrate chains in extracellular fragment, VLDL-R can be classified into two isoforms: VLDL-R Ⅰ with O-linker sugar region, while VLDL-R Ⅱ without this domain[1].But so far, the difference of their function and biological significance between two isoforms, especially those of VLDL-R Ⅱ has not been clarified. In our research, ldlA7 cell strains stably expressing two isoforms of VLDL-R were obtained through gene clone technology. Binding and internalization of the natural ligands (VLDL and β-VLDL)of two types VLDL-R and their roles in the formation of foam cells were compared to clarify the difference between two isoforms of VLDL-R, and elucidate their roles in the metabolism of lipoprotein and development of AS.

  13. Isolated hyperglycaemia does not increase VLDL-triacylglycerol secretion in type 1 diabetic men

    DEFF Research Database (Denmark)

    Johansen, Rakel Fuglsang; Søndergaard, Esben; Sørensen, Lars Peter

    2015-01-01

    AIMS/HYPOTHESIS: In type 1 diabetes, abnormalities of both glucose and lipoprotein metabolism are seen. The relationship between these factors is not understood, but studies indicate that hyperglycaemia may increase hepatic VLDL-triacylglycerol (VLDL-TG) secretion and reduce VLDL-TG fatty acid...... oxidation, which could lead to the development of dyslipidaemia. The aim of this study was to determine the isolated effect of hyperglycaemia on VLDL-TG and NEFA kinetics in men with type 1 diabetes. METHODS: VLDL-TG and palmitate kinetics were measured in eight men with type 1 diabetes using ex vivo...... of acute hyperglycaemia (16 mmol/l) without a concomitant increase in insulin does not alter VLDL-TG and NEFA kinetics in men with type 1 diabetes. Clinical trial registry number: NCT01178957....

  14. [Adipose triglyceride lipase regulates adipocyte lipolysis].

    Science.gov (United States)

    Xu, Chong; Xu, Guo-Heng

    2008-01-01

    Obesity, insulin resistance, and type 2 diabetes are associated with elevated concentration of circulating free fatty acids (FFAs), which are critically governed by the process of triglyceride lipolysis in adipocytes. Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) are two major enzymes in the control of triacylglycerol hydrolysis in adipose tissue. ATGL expressed predominantly in white adipose tissue specifically initiates triacylglycerol hydrolysis to generate diacylglycerols and FFA, a role distinguished from HSL that mainly hydrolyzes diacylglycerols. The transcription of ATGL is regulated by several factors. ATGL activity is regulated by CGI-58. Under basal conditions, interaction of CGI-58 with a lipid droplet associating protein, perilipin, results in an inactivation of ATGL activity. During PKA-stimulated lipolysis, CGI-58 is released from phosphorylated perilipin and in turn, binds to ATGL. This action facilitates triglyceride lipolysis. This review focuses on the regulation and function of ATGL in adipose lipolysis and metabolism.

  15. Glycerol inhibition of ruminal lipolysis in vitro

    Science.gov (United States)

    Supplemental glycerol inhibits rumen lipolysis, a prerequisite for rumen biohydrogenation, which is responsible for the saturation of dietary fatty acids consumed by ruminant animals. Feeding excess glycerol, however, adversely affects dry matter digestibility. To more clearly define the effect of...

  16. Effect of Alternative Splicing of VLDL Receptor on its Ligand Binding and Internalization Capability

    Institute of Scientific and Technical Information of China (English)

    2005-01-01

    1 IntroductionVery low density lipoprotein receptor (VLDL-R) is a main receptor mediating the uptake of triglyceride-rich lipoprotein(TRL), so it is in all probability to play an important role in the development of atherosclerosis (AS). On account of alternative splicing of O-linked carbohydrate chains in extracellular fragment, VLDL-R can be classified into two isoforms: VLDL-RⅠ with O-linker sugar region, while VLDL-RⅡ without this domain~([1]). But so far, the difference of their function and biological...

  17. Acute inhibition of hepatic beta-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity

    NARCIS (Netherlands)

    Duivenvoorden, [No Value; Teusink, B; Rensen, PCN; Kuipers, F; Romijn, JA; Havekes, LM; Voshol, PJ

    2005-01-01

    Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate ( MP), an inhibitor of ca

  18. Atorvastatin and Fenofibrate have Comparable Effects on VLDL-Apolipoprotein C-III Kinetics in Men with the Metabolic Syndrome

    Science.gov (United States)

    Chan, Dick C; Watts, Gerald F; Ooi, Esther M.M; Ji, Juying; Johnson, Anthony G; Barrett, P Hugh R

    2009-01-01

    Objectives The metabolic syndrome (MetS) is characterised by insulin resistance and dyslipidemia that may accelerate atherosclerosis. Disturbed apolipoprotein (apo) C-III metabolism may account for dyslipidemia in these subjects. Atorvastatin and fenofibrate decrease plasma apoC-III, but the underlying mechanisms are not fully understood. Methods and Results The effects of atorvastatin (40 mg/d) and fenofibrate (200mg/d) on the kinetics of very-low density lipoprotein (VLDL)-apoC-III were investigated in a cross-over trial of 11 MetS men. VLDL-apoC-III kinetics were studied, following intravenous d3-leucine administration using gas chromatography-mass spectrometry and compartmental modeling. Compared with placebo, both atorvastatin and fenofibrate significantly decreased (Ptriglyceride, apoB, apoB-48 and total apoC-III. Atorvastatin, not fenofibrate, significantly decreased plasma apoA-V concentrations (Pkinetics in MetS; reduced production and increased fractional catabolism of VLDL-apoC-III may explain the triglyceride-lowering effect of these agents. PMID:18566295

  19. VLDL from Metabolic Syndrome Individuals Enhanced Lipid Accumulation in Atria with Association of Susceptibility to Atrial Fibrillation

    Directory of Open Access Journals (Sweden)

    Hsiang-Chun Lee

    2016-01-01

    Full Text Available Metabolic syndrome (MetS represents a cluster of metabolic derangements. Dyslipidemia is an important factor in MetS and is related to atrial fibrillation (AF. We hypothesized that very low density lipoproteins (VLDL in MetS (MetS-VLDL may induce atrial dilatation and vulnerability to AF. VLDL was therefore separated from normal (normal-VLDL and MetS individuals. Wild type C57BL/6 male mice were divided into control, normal-VLDL (nVLDL, and MetS-VLDL (msVLDL groups. VLDL (15 µg/g and equivalent volumes of saline were injected via tail vein three times a week for six consecutive weeks. Cardiac chamber size and function were measured by echocardiography. MetS-VLDL significantly caused left atrial dilation (control, n = 10, 1.64 ± 0.23 mm; nVLDL, n = 7, 1.84 ± 0.13 mm; msVLDL, n = 10, 2.18 ± 0.24 mm; p < 0.0001 at week 6, associated with decreased ejection fraction (control, n = 10, 62.5% ± 7.7%, vs. msVLDL, n = 10, 52.9% ± 9.6%; p < 0.05. Isoproterenol-challenge experiment resulted in AF in young msVLDL mice. Unprovoked AF occurred only in elderly msVLDL mice. Immunohistochemistry showed excess lipid accumulation and apoptosis in msVLDL mice atria. These findings suggest a pivotal role of VLDL in AF pathogenesis for MetS individuals.

  20. IRE1α-XBP1s induces PDI expression to increase MTP activity for hepatic VLDL assembly and lipid homeostasis.

    Science.gov (United States)

    Wang, Shiyu; Chen, Zhouji; Lam, Vivian; Han, Jaeseok; Hassler, Justin; Finck, Brian N; Davidson, Nicholas O; Kaufman, Randal J

    2012-10-03

    The unfolded protein response (UPR) is a signaling pathway required to maintain endoplasmic reticulum (ER) homeostasis and hepatic lipid metabolism. Here, we identify an essential role for the inositol-requiring transmembrane kinase/endoribonuclease 1α (IRE1α)-X box binding protein 1 (XBP1) arm of the UPR in regulation of hepatic very low-density lipoprotein (VLDL) assembly and secretion. Hepatocyte-specific deletion of Ire1α reduces lipid partitioning into the ER lumen and impairs the assembly of triglyceride (TG)-rich VLDL but does not affect TG synthesis, de novo lipogenesis, or the synthesis or secretion of apolipoprotein B (apoB). The defect in VLDL assembly is, at least in part, due to decreased microsomal triglyceride-transfer protein (MTP) activity resulting from reduced protein disulfide isomerase (PDI) expression. Collectively, our findings reveal a key role for the IRE1α-XBP1s-PDI axis in linking ER homeostasis with regulation of VLDL production and hepatic lipid homeostasis that may provide a therapeutic target for disorders of lipid metabolism.

  1. The binding of human lipoprotein lipase treated VLDL by the human hepatoma cell line HepG2

    NARCIS (Netherlands)

    Mulder, M.; Wit, E.de; Havekes, L.M.

    1991-01-01

    It has been suggested that besides the LDL-receptor, hepatocytes possess an apo E or remnant receptor. To evaluate which hepatic lipoprotein receptor is involved in VLDL remnant catabolism, we studied the binding of VLDL remnants to HepG2 cells. Native VLDL was obtained from type IIb hyperlipidemic

  2. Role of VLDL Receptor in the Process of Foam Cell Formation

    Institute of Scientific and Technical Information of China (English)

    屈伸; 吴凡; 田俊; 李映红; 王燕; 王宇哲; 宗义强

    2004-01-01

    Summary: The role of very low density lipoprotein receptor (LVLDR) in the process of foam cell formation was investigated. After the primary cultured mouse peritoneal macrophages were incubated with VLDL, β-VLDL or low density lipoprotein (LDL), respectively for 24 h and 48 h, foam cells formation was identified by oil red O staining and cellular contents of triglyceride (TG) and total cholesterol (TC) were determined. The mRNA levels of LDLR, LDLR related protein (LRP)and VLDLR were detected by semi-quantitative RT-PCR. The results demonstrated that VLDL, βVLDL and LDL could increase the contents of TG and TC in macrophages. Cells treated with VLDL or β-VLDL showed markedly increased expression of VLDLR and decreased expression of LDLR, whereas LRP was up-regulated slightly. For identifying the effect of VLDL receptor on cellular lipid accumulation, Idl-A7-VR cells, which expresses VLDLR and trace amount of LRP without functional LDLR, was used to incubate with lipoproteins for further examination. The results elucidated that the uptake of triglyceride-rich lipoprotein mediated by VLDLR plays an important role in accumulation of lipid and the formation of foam cells.

  3. Loss of fat with increased adipose triglyceride lipase-mediated lipolysis in adipose tissue during laying stages in quail.

    Science.gov (United States)

    Yang, Shujin; Suh, Yeunsu; Choi, Young Min; Shin, Sangsu; Han, Jae Yong; Lee, Kichoon

    2013-01-01

    The goal of the current study was to investigate regulation of key genes involved in lipid metabolism in adipose and liver to relate lipolytic and lipogenic capacities with physiological changes at the pre-laying, onset of laying, and actively laying stages of quail. Followed by a 50 % increase from pre-laying to onset of laying, adipose to body weight ratio was significantly reduced by 60 % from the onset of laying to the actively laying stage (P quail, increased protein expression and phosphorylation of adipose triglyceride lipase (ATGL) together with an elevated mRNA expression of comparative gene identification-58, an activator of ATGL, contributes to increased lipolytic activity, as proved by increased amounts of plasma non-esterified fatty acid (P quail could contribute to the adipocyte hypotrophy (P quail. These results suggest that the laying birds undergo active lipolysis in the adipocyte, and increase VLDL secretion from the liver in order to secure a lipid supply for yolk maturation.

  4. GLP-1 receptor agonism ameliorates hepatic VLDL overproduction and de novo lipogenesis in insulin resistance

    Directory of Open Access Journals (Sweden)

    Jennifer Taher

    2014-12-01

    Conclusion: Exendin-4 prevents fructose-induced dyslipidemia and hepatic VLDL overproduction in insulin resistance through an indirect mechanism involving altered energy utilization, decreased hepatic lipid synthesis and also requires an intact parasympathetic signaling pathway.

  5. Increased VLDL-TG fatty acid storage in skeletal muscle in men with type 2 diabetes

    DEFF Research Database (Denmark)

    Andersen, Iben R; Søndergaard, Esben; Sørensen, Lars P

    2016-01-01

    -TG storage rate and LPL activity or other storage factors in muscle or adipose tissue. However, LPL activity correlated with fractional VLDL-TG storage in abdominal fat (p=0.04). CONCLUSIONS: Men with type 2 diabetes have increased VLDL-TG storage in muscle tissue, potentially contributing to increased......CONTEXT: Lipoprotein lipase (LPL) activity is considered the rate-limiting step of very-low-density-lipoprotein triglycerides (VLDL-TG) tissue storage, and has been suggested to relate to the development of obesity as well as insulin resistance and type 2 diabetes. OBJECTIVE: The objective...... of the study was to assess the relationship between the quantitative storage of VLDL-TG fatty acids and LPL activity and other storage factors in muscle and adipose tissue. In addition, we examine whether such relations were influenced by type 2 diabetes. DESIGN: 23 men (12 with type 2 diabetes, 11 non...

  6. Digestion of microencapsulated oil powders: in vitro lipolysis and in vivo absorption from a food matrix.

    Science.gov (United States)

    Augustin, Mary Ann; Sanguansri, Luz; Rusli, Jenny Kartika; Shen, Zhiping; Cheng, Li Jiang; Keogh, Jennifer; Clifton, Peter

    2014-11-01

    Microencapsulation provides a vehicle for the incorporation of fats and oils into powders that can be used as dry ingredients in an expanded variety of food products. Microencapsulated omega-3 oils in particular are commonly incorporated into a variety of foods and numerous in vitro studies have examined the impact of individual microencapsulation technologies on the simulated digestibility of the oil core. We have exposed twelve microencapsulated canola oil-in-water emulsions, formulated with different proteins (milk or soy) or mixtures of protein and carbohydrates (sugars, oligosaccharides, resistant starch) and processed into powders by spray drying, to simulated gastric and intestinal fluids in vitro. The extent of lipolysis of the canola oil in these products varied between 12-68% suggesting that the in vitro digestibility of the oil within the powders was dependent on both the formulation and the processing steps used in their manufacture. Five microencapsulated powders with differing extents of in vitro lipolysis were then incorporated into a dairy beverage for an in vivo human trial with neat oil incorporation in the beverage used as the control. Measurement of triglyceride levels in blood revealed both enhanced peak height and area under the curve (AUC) in vivo for the microencapsulated oil groups when compared to the neat oil control. The range of lipolysis efficiencies observed with the different formulations in vitro was not reflected in vivo. These observations suggest that care needs to be taken when extrapolating data from in vitro lipolysis to bioavailability in humans.

  7. Lipolysis in human adipose tissue during exercise

    DEFF Research Database (Denmark)

    Lange, Kai Henrik Wiborg; Lorentsen, Jeanne; Isaksson, Fredrik

    2002-01-01

    Subcutaneous adipose tissue lipolysis was studied in vivo by Fick's arteriovenous (a-v) principle using either calculated (microdialysis) or directly measured (catheterization) adipose tissue venous glycerol concentration. We compared results during steady-state (rest and prolonged continuous...... exercise), as well as during non-steady-state (onset of exercise and early exercise) experimental settings. Fourteen healthy women [age: 74 +/- 1 (SE) yr] were studied at rest and during 60-min continuous bicycling at 60% of peak O(2) uptake. Calculated and measured subcutaneous abdominal adipose tissue...... adipose tissue venous glycerol concentration. Despite several methodological limitations inherent to both techniques, the results strongly suggest that microdialysis and catheterization provide similar estimates of subcutaneous adipose tissue lipolysis in steady-state experimental settings like rest...

  8. Treatment of lipoma by injection lipolysis.

    Science.gov (United States)

    Nanda, Soni

    2011-05-01

    Injection lipolysis or lipodissolve is the practice of injecting phosphatidyl choline/ sodium deoxycholate (PDC/DC) compounds in the subcutaneous fat. Though this practice is being used extensively for nonsurgical contouring of body and dissolving localized collections of excess fat, it's use as a treatment modality for lipomas needs further evaluation. We present a case where this technique was used for treating a lipoma, with no recurrence after 9 months of follow up. Injection lipolysis as a treatment modality for lipomas needs to be evaluated for safety and efficacy in trials on larger population. This could prove to be a very valuable adjunct to the current practice of excision, if done by a trained person in a properly selected patient. Also the side effects and the controversies regarding this procedure have been discussed in detail in the present paper.

  9. Physiological regulation of NEFA availability: lipolysis pathway.

    Science.gov (United States)

    Stich, V; Berlan, M

    2004-05-01

    Plasma NEFA are an important energy substrate and, furthermore, play a key role in the induction of insulin resistance in the body. The availability of NEFA is determined predominantly by their mobilization from adipose tissue triacylglycerol stores by the process of lipolysis. Adipose tissue lipolysis in man is regulated by a number of hormonal and paracrine and/or autocrine signals. The main hormonal signals may be represented by catecholamines, insulin, growth hormone, natriuretic peptides and some adipocytokines. The absolute levels and relative importance and contribution of these signals vary in different physiological situations, with diet and physical exercise being the main physiological variables that affect the hormonal signalling. Thus, modulations in hormonal signals induce an increase in NEFA mobilization in the post-absorptive state and during an acute bout of exercise, and suppress NEFA mobilization in the postprandial state. In addition, hormonal regulation is modified by long-term interventions in energy balance, such as dietary restriction and/or physical training, and is disturbed in some pathological states, such as obesity or diabetes. The question that remains is whether disturbances in lipolysis regulation in obese and diabetic subjects may be 'corrected' by the long-term interventions in diet and physical activity.

  10. Curcumin inhibits lipolysis via suppression of ER stress in adipose tissue and prevents hepatic insulin resistance.

    Science.gov (United States)

    Wang, Lulu; Zhang, Bangling; Huang, Fang; Liu, Baolin; Xie, Yuan

    2016-07-01

    Curcumin is natural polyphenol with beneficial effects on lipid and glucose metabolism and this study aimed to investigate the effects of curcumin on lipolysis and hepatic insulin resistance. Endoplasmic reticulum (ER) stress and lipolysis signaling in adipose and FFA influx, lipid deposits, and glucose production in liver were examined. Palmitate challenge and high-fat diet feeding evoked ER stress-associated lipolysis with cAMP accumulation in adipose tissue. Curcumin treatment inhibited adipose tissue ER stress by dephosphorylation of inositol-requiring enzyme 1α and eukaryotic initiation factor 2α and reduced cAMP accumulation by preserving phosphodiesterase 3B induction. Knockdown of mitogen-activated protein kinase α1/2α with siRNAs diminished such effects of curcumin. As a result from downregulation of cAMP, curcumin blocked protein kinase (PK)A/hormone-sensitive lipase lipolysis signaling, and thereby reduced glycerol and FFA release from adipose tissue. Curcumin reduced FFA influx into the liver by blocking FFA trafficking, and then prevented diacylglycerol deposits and PKCε translocation in the liver, resultantly improving insulin action in the suppression of hepatic gluconeogenesis. Curcumin decreased adipose lipolysis by attenuating ER stress through the cAMP/PKA pathway, reduced FFA influx into the liver by blocking FFA trafficking, and thereby improved insulin sensitivity to inhibit hepatic glucose production. These findings suggested a novel pathway of curcumin to prevent lipid deposits and insulin resistance in liver by beneficial regulation of adipose function. Copyright © 2016 by the American Society for Biochemistry and Molecular Biology, Inc.

  11. Kinetics of ruminal lipolysis of triacylglycerol and biohydrogenation of long-chain fatty acids: new insights from old data.

    Science.gov (United States)

    Moate, P J; Boston, R C; Jenkins, T C; Lean, I J

    2008-02-01

    Previous investigations into ruminal lipolysis of triacylglycerol and ruminal biohydrogenation (BH) of unsaturated long-chain fatty acids have generally quantified these processes with either zero-order or first-order kinetics. This investigation examined if Michaelis-Menten and other nonlinear kinetics might be useful for quantifying these processes. Data from 2 previously published in vitro experiments employing rumen fluid from sheep to investigate the lipolysis of trilinolein, the BH of cis-9, cis-12 linoleic acid (LA), and the BH of fatty acids derived from the lipolysis of trilinolein were used for the development of a multi-compartmental model. The model described the lipolysis of triacylglycerol well. The model also provided a good mathematical description of the resulting production of nonesterified fatty acids, the isomerization of nonesterified LA, and subsequent production of rumenic acid (RA), vaccenic acid (VA), and stearic acid (SA). However, the model described poorly the patterns of the concentrations of LA, RA, VA, and SA after incubation of trilinolein in rumen fluid. The model is consistent with known stoichiometry and biochemistry and is parsimonious in that it employs a minimal number of parameters to describe all of the major aspects of lipolysis and BH. The first step in the lipolysis of trilinolein was described by Michaelis-Menten kinetics (Vmax = 529 +/- 16 mg/L per h; Km = 698 +/- 41 mg/L). Both subsequent lipolysis steps were approximated by a first-order (linear kinetics) rate constant (k = 2.64 +/- 0.041 /h). Isomerization of LA to RA was modeled by simple Michaelis-Menten kinetics (Vmax = 2,421 +/- 83 mg/L per h; Km = 440 +/- 22 mg/L). The kinetics of the BH of RA to VA was described by a Michaelis-Menten-type process involving competitive inhibition by VA (Vmax = 492 +/- 6.5 mg/L per h; Km = 1 mg/L). The final step, the BH of VA to SA, was modeled by a quasi-first-order process (k = 0.533 +/- 0.021 /h), but as the concentration of

  12. Adipocyte lipases and defect of lipolysis in human obesity.

    Science.gov (United States)

    Langin, Dominique; Dicker, Andrea; Tavernier, Geneviève; Hoffstedt, Johan; Mairal, Aline; Rydén, Mikael; Arner, Erik; Sicard, Audrey; Jenkins, Christopher M; Viguerie, Nathalie; van Harmelen, Vanessa; Gross, Richard W; Holm, Cecilia; Arner, Peter

    2005-11-01

    The mobilization of fat stored in adipose tissue is mediated by hormone-sensitive lipase (HSL) and the recently characterized adipose triglyceride lipase (ATGL), yet their relative importance in lipolysis is unknown. We show that a novel potent inhibitor of HSL does not inhibit other lipases. The compound counteracted catecholamine-stimulated lipolysis in mouse adipocytes and had no effect on residual triglyceride hydrolysis and lipolysis in HSL-null mice. In human adipocytes, catecholamine- and natriuretic peptide-induced lipolysis were completely blunted by the HSL inhibitor. When fat cells were not stimulated, glycerol but not fatty acid release was inhibited. HSL and ATGL mRNA levels increased concomitantly during adipocyte differentiation. Abundance of the two transcripts in human adipose tissue was highly correlated in habitual dietary conditions and during a hypocaloric diet, suggesting common regulatory mechanisms for the two genes. Comparison of obese and nonobese subjects showed that obesity was associated with a decrease in catecholamine-induced lipolysis and HSL expression in mature fat cells and in differentiated preadipocytes. In conclusion, HSL is the major lipase for catecholamine- and natriuretic peptide-stimulated lipolysis, whereas ATGL mediates the hydrolysis of triglycerides during basal lipolysis. Decreased catecholamine-induced lipolysis and low HSL expression constitute a possibly primary defect in obesity.

  13. Resveratrol regulates lipolysis via adipose triglyceride lipase.

    Science.gov (United States)

    Lasa, Arrate; Schweiger, Martina; Kotzbeck, Petra; Churruca, Itziar; Simón, Edurne; Zechner, Rudolf; Portillo, María del Puy

    2012-04-01

    Resveratrol has been reported to increase adrenaline-induced lipolysis in 3T3-L1 adipocytes. The general aim of the present work was to gain more insight concerning the effects of trans-resveratrol on lipid mobilization. The specific purpose was to assess the involvement of the two main lipases: adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), in the activation of lipolysis induced by this molecule. For lipolysis experiments, 3T3-L1 and human SGBS adipocytes as well as adipose tissue from wild-type, ATGL knockout and HSL knockout mice were used. Moreover, gene and protein expressions of these lipases were analyzed. Resveratrol-induced free fatty acids release but not glycerol release in 3T3-L1 under basal and isoproterenol-stimulating conditions and under isoproterenol-stimulating conditions in SGBS adipocytes. When HSL was blocked by compound 76-0079, free fatty acid release was still induced by resveratrol. By contrast, in the presence of the compound C, an inhibitor of adenosine monophosphate-activated protein kinase, resveratrol effect was totally blunted. Resveratrol increased ATGL gene and protein expressions, an effect that was not observed for HSL. Resveratrol increased fatty acids release in epididymal adipose tissue from wild-type and HSL knockout mice but not in that adipose tissue from ATGL knockout mice. Taking as a whole, the present results provide novel evidence that resveratrol regulates lipolytic activity in human and murine adipocytes, as well as in white adipose tissue from mice, acting mainly on ATGL at transcriptional and posttranscriptional levels. Enzyme activation seems to be induced via adenosine monophosphate-activated protein kinase. Copyright © 2012 Elsevier Inc. All rights reserved.

  14. Rosiglitazone regulates IL-6-stimulated lipolysis in porcine adipocytes.

    Science.gov (United States)

    Yang, Yongqing; Yang, Gongshe

    2010-10-01

    Interleukin (IL)-6, a proinflammatory cytokine, stimulates adipocyte lipolysis and induces insulin resistance in obese and diabetic subjects. However, the effects of the anti-diabetic drug rosiglitazone on IL-6-stimulated lipolysis and the underlying molecular mechanism are largely unknown. In this study, we demonstrated that rosiglitazone suppressed IL-6-stimulated lipolysis in differentiated porcine adipocytes by inactivation of extracellular signal-related kinase (ERK). Meanwhile, rosiglitazone enhanced the lipolysis response of adipocytes to isoprenaline. In addition, rosiglitazone significantly reversed IL-6-induced down-regulation of several genes such as perilipin A, peroxisome proliferators activated receptor gamma (PPARγ), and fatty acid synthetase, as well as the up-regulation of IL-6 mRNA. However, mRNA expression of PPARγ coactivator-1 alpha (PCG-1α) was enhanced by rosiglitazone in IL-6-stimulated adipocytes. These results indicate that rosiglitazone suppresses IL-6-stimulated lipolysis in porcine adipocytes through multiple molecular mechanisms.

  15. Hypothalamic neuropeptide Y (NPY) controls hepatic VLDL-triglyceride secretion in rats via the sympathetic nervous system

    NARCIS (Netherlands)

    Bruinstroop, E.; Pei, L.; Ackermans, M.T.; Foppen, E.; Borgers, A.J.F.; Kwakkel, J.; Alkemade, A.; Fliers, E.; Kalsbeek, A.

    2012-01-01

    Excessive secretion of triglyceride-rich very low-density lipoproteins (VLDL-TG) contributes to diabetic dyslipidemia. Earlier studies have indicated a possible role for the hypothalamus and autonomic nervous system in the regulation of VLDL-TG. In the current study, we investigated whether the auto

  16. Binding of β-VLDL to heparan sulfate proteoglycans requires lipoprotein lipase, whereas apoE only modulates binding affinity

    NARCIS (Netherlands)

    Beer, F. de; Hendriks, W.L.; Vark, L.C. van; Kamerling, S.W.A.; Dijk, K.W. van; Hofker, M.H.; Smelt, A.H.M.; Havekes, L.M.

    1999-01-01

    The binding of β-VLDL to heparan sulfate proteoglycans (HSPG) has been reported to be stimulated by both apoE and lipoprotein lipase (LPL). In the present study we investigated the effect of the isoform and the amount of apoE per particle, as well as the role of LPL on the binding of β-VLDL to HSPG.

  17. Comparison of FTIR-ATR and Raman spectroscopy in determination of VLDL triglycerides in blood serum with PLS regression

    Science.gov (United States)

    Oleszko, Adam; Hartwich, Jadwiga; Wójtowicz, Anna; Gąsior-Głogowska, Marlena; Huras, Hubert; Komorowska, Małgorzata

    2017-08-01

    Hypertriglyceridemia, related with triglyceride (TG) in plasma above 1.7 mmol/L is one of the cardiovascular risk factors. Very low density lipoproteins (VLDL) are the main TG carriers. Despite being time consuming, demanding well-qualified staff and expensive instrumentation, ultracentrifugation technique still remains the gold standard for the VLDL isolation. Therefore faster and simpler method of VLDL-TG determination is needed. Vibrational spectroscopy, including FT-IR and Raman, is widely used technique in lipid and protein research. The aim of this study was assessment of Raman and FT-IR spectroscopy in determination of VLDL-TG directly in serum with the isolation step omitted. TG concentration in serum and in ultracentrifugated VLDL fractions from 32 patients were measured with reference colorimetric method. FT-IR and Raman spectra of VLDL and serum samples were acquired. Partial least square (PLS) regression was used for calibration and leave-one-out cross validation. Our results confirmed possibility of reagent-free determination of VLDL-TG directly in serum with both Raman and FT-IR spectroscopy. Quantitative VLDL testing by FT-IR and/or Raman spectroscopy applied directly to maternal serum seems to be promising screening test to identify women with increased risk of adverse pregnancy outcomes and patient friendly method of choice based on ease of performance, accuracy and efficiency.

  18. Effects of fish oil on oxidation resistance of VLDL in hypertriglyceridemic patients

    NARCIS (Netherlands)

    Hau, M.-F.; Smelt, A.H.M.; Bindels, A.J.G.H.; Sijbrands, E.J.G.; Laarse, A. van der; Onkenhout, W.; Duyvenvoorde, W. van; Princen, H.M.G.

    1996-01-01

    In hypertriglyceridemic (HTG) patients the addition of fish oil to the diet causes a marked reduction in the concentration of triglyceride-rich lipoproteins in the serum. To investigate the effects of fish oil on the oxidation resistance of VLDL and LDL in HTG patients, nine male patients received 1

  19. Mea6 controls VLDL transport through the coordinated regulation of COPII assembly

    Science.gov (United States)

    Wang, Yaqing; Liu, Liang; Zhang, Hongsheng; Fan, Junwan; Zhang, Feng; Yu, Mei; Shi, Lei; Yang, Lin; Lam, Sin Man; Wang, Huimin; Chen, Xiaowei; Wang, Yingchun; Gao, Fei; Shui, Guanghou; Xu, Zhiheng

    2016-01-01

    Lipid accumulation, which may be caused by the disturbance in very low density lipoprotein (VLDL) secretion in the liver, can lead to fatty liver disease. VLDL is synthesized in endoplasmic reticulum (ER) and transported to Golgi apparatus for secretion into plasma. However, the underlying molecular mechanism for VLDL transport is still poorly understood. Here we show that hepatocyte-specific deletion of meningioma-expressed antigen 6 (Mea6)/cutaneous T cell lymphoma-associated antigen 5C (cTAGE5C) leads to severe fatty liver and hypolipemia in mice. Quantitative lipidomic and proteomic analyses indicate that Mea6/cTAGE5 deletion impairs the secretion of different types of lipids and proteins, including VLDL, from the liver. Moreover, we demonstrate that Mea6/cTAGE5 interacts with components of the ER coat protein complex II (COPII) which, when depleted, also cause lipid accumulation in hepatocytes. Our findings not only reveal several novel factors that regulate lipid transport, but also provide evidence that Mea6 plays a critical role in lipid transportation through the coordinated regulation of the COPII machinery. PMID:27311593

  20. Effects of fish oil on oxidation resistance of VLDL in hypertriglyceridemic patients

    NARCIS (Netherlands)

    Hau, M.-F.; Smelt, A.H.M.; Bindels, A.J.G.H.; Sijbrands, E.J.G.; Laarse, A. van der; Onkenhout, W.; Duyvenvoorde, W. van; Princen, H.M.G.

    1996-01-01

    In hypertriglyceridemic (HTG) patients the addition of fish oil to the diet causes a marked reduction in the concentration of triglyceride-rich lipoproteins in the serum. To investigate the effects of fish oil on the oxidation resistance of VLDL and LDL in HTG patients, nine male patients received 1

  1. The Binding Ability Analysis of the Normal VLDL Receptor and Its Mutant

    Institute of Scientific and Technical Information of China (English)

    QU Shen; FENG Ning; LIU Zhiguo; ZHOU Hua; DENG Yaozu; FENG Zongchen

    2001-01-01

    The ligand-binding domain of VLDL receptor contains eight imperfectly similar repeats.To discuss the contribution of each repeat to ligand binding, the RT-PCR technique was used to clone the VLDLR-cDNA from the heart muscle of Chinese people. Two recombinants were further constructed, which contained the full-length cDNA of VLDLR and the mutant lacking repeats 1-5.CHO cell line was transfected with two recombinants. The expression of VLDLR gene could be detected by RT-PCR from the CHO cells transfected with pCD-VR. The results of binding experiments showed that the ability of the CHO cells transfected with the full-length cDNA of VLDL-R binding DiI-labeled β-VLDL was higher than that of the CHO cells transfected with the mutant. Our findings indicated that human VLDL-R gene could be expressed effectively on CHO cells, and the receptor was almost inactivated when repeats1-5 were deleted.

  2. The effect of interaction between Lipoprotein Lipase and ApoVLDL-II ...

    African Journals Online (AJOL)

    GREGO

    2007-04-02

    Apr 2, 2007 ... non-significantly different in fat chicken. SNP in apoVLDL-II and ... stage in the control of adipose tissue accretion is the removal of triglycerides ..... of absorbed fat is the same, lower body fat deposition may be attributed to.

  3. Metformin lowers plasma triglycerides by promoting vldl-triglyceride clearance by brown adipose tissue in mice

    NARCIS (Netherlands)

    Geerling, J.J.; Boon, M.R.; Zon, G.C. van der; Berg, S.A.A. van den; Hoek, A.M. van den; Lombès, M.; Princen, H.M.G.; Havekes, L.M.; Rensen, P.C.N.; Guigas, B.

    2014-01-01

    Metformin is the first-line drug for the treatment of type 2 diabetes. Besides its well-characterized antihyperglycemic properties, metformin also lowers plasma VLDL triglyceride (TG). In this study, we investigated the underlying mechanisms in APOE*3-Leiden.CETP mice, a well-established model for h

  4. Increased and early lipolysis in children with long-chain 3-hydroxyacyl-CoA dehydrogenase (LCHAD) deficiency during fast.

    Science.gov (United States)

    Haglind, C Bieneck; Nordenström, A; Ask, S; von Döbeln, U; Gustafsson, J; Stenlid, M Halldin

    2015-03-01

    Children with long-chain 3-hydroxyacyl-CoA dehydrogenase deficiency (LCHAD) have a defect in the degradation of long-chain fatty acids and are at risk of hypoketotic hypoglycemia and insufficient energy production as well as accumulation of toxic fatty acid intermediates. Knowledge on substrate metabolism in children with LCHAD deficiency during fasting is limited. Treatment guidelines differ between centers, both as far as length of fasting periods and need for night feeds are concerned. To increase the understanding of fasting intolerance and improve treatment recommendations, children with LCHAD deficiency were investigated with stable isotope technique, microdialysis, and indirect calometry, in order to assess lipolysis and glucose production during 6 h of fasting. We found an early and increased lipolysis and accumulation of long chain acylcarnitines after 4 h of fasting, albeit no patients developed hypoglycemia. The rate of glycerol production, reflecting lipolysis, averaged 7.7 ± 1.6 µmol/kg/min, which is higher compared to that of peers. The rate of glucose production was normal for age; 19.6 ± 3.4 µmol/kg/min (3.5 ± 0.6 mg/kg/min). Resting energy expenditure was also normal, even though the respiratory quotient was increased indicating mainly glucose oxidation. The results show that lipolysis and accumulation of long chain acylcarnitines occurs before hypoglycemia in fasting children with LCHAD, which may indicate more limited fasting tolerance than previously suggested.

  5. Subcutaneous Adipocyte Lipolysis Contributes to Circulating Lipid Levels.

    Science.gov (United States)

    Rydén, Mikael; Arner, Peter

    2017-09-01

    Fatty acids released via fat cell lipolysis can affect circulating lipid levels. However, the contribution of different lipolysis measures in adipose tissue is unknown and was presently examined in isolated subcutaneous adipocytes. One thousand and sixty-six men and women were examined for lipolysis regulation in subcutaneous abdominal fat cells. Results were compared with fasting plasma levels of total cholesterol, high-density lipoprotein (HDL) cholesterol (HDL-C) and triglycerides. Spontaneous (basal) lipolysis and the effects of the major hormones stimulating (catecholamines and natriuretic peptides) and inhibiting lipolysis (insulin) were examined. Several statistically significant (Plipolysis parameters and plasma lipids were observed. However, physiologically relevant correlations (adjusted r(2)≥0.05) were only evident between basal or insulin-inhibited lipolysis and plasma triglycerides or HDL-C. Together, these lipolysis measures explained 14% of the variation in triglycerides or HDL-C, respectively. In comparison, a combination of established factors associated with variations in plasma lipids, that is, age; body mass index; waist circumference; waist-to-hip ratio; sex; nicotine use; fat cell volume; and pharmacotherapy against diabetes mellitus; hypertension; or hyperlipidemia explained 17% and 28%, respectively, of the variations in plasma triglycerides and HDL-C. Subcutaneous fat cell lipolysis is an important independent contributor to interindividual variations in plasma lipids. High spontaneous lipolysis activity and resistance to the antilipolytic effect of insulin associate with elevated triglyceride and low HDL-C concentrations. Thus, although several other factors also play a role, subcutaneous adipose tissue may have a causal influence on dyslipidemia. © 2017 The Authors.

  6. Impaired atrial natriuretic peptide-mediated lipolysis in obesity.

    Science.gov (United States)

    Rydén, M; Bäckdahl, J; Petrus, P; Thorell, A; Gao, H; Coue, M; Langin, D; Moro, C; Arner, P

    2016-04-01

    Catecholamines and natriuretic peptides (NPs) are the only hormones with pronounced lipolytic effects in human white adipose tissue. Although catecholamine-induced lipolysis is well known to be impaired in obesity and insulin resistance, it is not known whether the effect of NPs is also altered. Catecholamine- and atrial NP (ANP)-induced lipolysis was investigated in abdominal subcutaneous adipocytes in vitro and in situ by microdialysis. In a cohort of 122 women, both catecholamine- and ANP-induced lipolysis in vitro was markedly attenuated in obesity (n=87), but normalized after substantial body weight loss (n=52). The impairment of lipolysis differed between the two hormones when expressing lipolysis per lipid weight, the ratio of stimulated over basal (spontaneous) lipolysis rate or per number of adipocytes. Thus, while the response to catecholamines was lower when expressed as the former two measures, it was higher when expressed per cell number, a consequence of the significantly larger fat cell size in obesity. In contrast, although ANP-induced lipolysis was also attenuated when expressed per lipid weight or the ratio stimulated/basal, it was similar between non-obese and obese subjects when expressed per cell number suggesting that the lipolytic effect of ANP may be even more sensitive to the effects of obesity than catecholamines. Obesity was characterized by a decrease in the protein expression of the signaling NP A receptor (NPRA) and a trend toward increased levels of the clearance receptor NPRC. The impairment in ANP-induced lipolysis observed in vitro was corroborated by microdialysis experiments in situ in a smaller cohort of lean and overweight men. ANP- and catecholamine-induced lipolysis is reversibly attenuated in obesity. The pro-lipolytic effects of ANP are relatively more impaired compared with that of catecholamines, which may in part be due to specific changes in NP receptor expression.

  7. Both lipolysis and hepatic uptake of VLDL are impaired in transgenic mice coexpressing human apolipoprotein E*3Leiden and human apolipoprotein C1

    NARCIS (Netherlands)

    Jong, M.C.; Dahlmans, V.E.H.; Gorp, P.J.J. van; Breuer, M.L.; Mol, M.J.T.M.; Zee, A. van der; Frants, R.R.; Hofker, M.H.; Havekes, L.M.

    1996-01-01

    Transgenic mice overexpressing human APOE*3Leiden are highly susceptible to diet-induced hyperlipoproteinemia and atherosclerosis due to a defect in hepatic uptake of remnant lipoproteins. In addition to the human APOE*3Leiden gene, these mice carry the human APOC1 gene (APOE*3Leiden- C1). To

  8. Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue.

    Science.gov (United States)

    Zhou, Shui-Rong; Guo, Liang; Wang, Xu; Liu, Yang; Peng, Wan-Qiu; Liu, Yuan; Wei, Xiang-Bo; Dou, Xin; Ding, Meng; Lei, Qun-Ying; Qian, Shu-Wen; Li, Xi; Tang, Qi-Qun

    2017-08-15

    White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT. Copyright © 2017 American Society for Microbiology.

  9. Nutritional repletion of children with severe acute malnutrition does not affect VLDL apolipoprotein B-100 synthesis rate.

    Science.gov (United States)

    Badaloo, Asha V; Forrester, Terrence; Reid, Marvin; Jahoor, Farook

    2012-05-01

    VLDL apo B-100 is essential for the secretion of liver fat. It is thought that synthesis of this lipoprotein is impaired in childhood severe acute malnutrition (SAM), especially in the edematous syndromes, and that this contributes to the common occurrence of hepatic steatosis in this condition. However, to our knowledge, it has not been confirmed that VLDL apo B-100 synthesis is slower in edematous compared with nonedematous SAM and that it is impaired in the malnourished compared with the well-nourished state. Therefore, VLDL apo B-100 kinetics were measured in 2 groups of children with SAM (15 edematous and 7 nonedematous), aged 4-20 mo, at 3 stages during treatment. Measurements were done at 4 ± 1 d postadmission, mid- catch-up growth in weight, and at recovery (normal weight-for-length). VLDL apo B-100 synthesis was determined using stable isotope methodology to measure the rate of incorporation of (2)H(3)-leucine into its apoprotein moiety. The fractional and absolute synthesis of VLDL apo B-100 did not differ between the groups or from the initial malnourished stage to the recovery stage. Concentrations of VLDL apo B-100 were greater in the edematous than in the nonedematous group (P < 0.04) and did not differ from the initial stage to recovery. The data indicate that VLDL apo B-100 synthesis is not reduced when children develop either edematous or nonedematous SAM.

  10. Lipolysis and lipid mobilization in human adipose tissue.

    Science.gov (United States)

    Lafontan, Max; Langin, Dominique

    2009-09-01

    Triacylglycerol (TAG) stored in adipose tissue (AT) can be rapidly mobilized by the hydrolytic action of the three main lipases of the adipocyte. The non-esterified fatty acids (NEFA) released are used by other tissues during times of energy deprivation. Until recently hormone-sensitive lipase (HSL) was considered to be the key rate-limiting enzyme responsible for regulating TAG mobilization. A novel lipase named adipose triglyceride lipase/desnutrin (ATGL) has been identified as playing an important role in the control of fat cell lipolysis. Additionally perilipin and other proteins of the surface of the lipid droplets protecting or exposing the TAG core of the droplets to lipases are also potent regulators of lipolysis. Considerable progress has been made in understanding the mechanisms of activation of the various lipases. Lipolysis is under tight hormonal regulation. The best understood hormonal effects on AT lipolysis concern the opposing regulation by insulin and catecholamines. Heart-derived natriuretic peptides (i.e., stored in granules in the atrial and ventricle cardiomyocytes and exerting stimulating effects on diuresis and natriuresis) and numerous autocrine/paracrine factors originating from adipocytes and other cells of the stroma-vascular fraction may also participate in the regulation of lipolysis. Endocrine and autocrine/paracrine factors cooperate and lead to a fine regulation of lipolysis in adipocytes. Age, anatomical site, sex, genotype and species differences all play a part in the regulation of lipolysis. The manipulation of lipolysis has therapeutic potential in the metabolic disorders frequently associated with obesity and probably in several inborn errors of metabolism.

  11. Lipolysis and lipases in white adipose tissue – An update

    OpenAIRE

    Bolsoni-Lopes,Andressa; Alonso-Vale, Maria Isabel C.

    2015-01-01

    Lipolysis is defined as the sequential hydrolysis of triacylglycerol (TAG) stored in cell lipid droplets. For many years, it was believed that hormone-sensitive lipase (HSL) and monoacylglycerol lipase (MGL) were the main enzymes catalyzing lipolysis in the white adipose tissue. Since the discovery of adipose triglyceride lipase (ATGL) in 2004, many studies were performed to investigate and characterize the actions of this lipase, as well as of other proteins and possible regulatory mechanism...

  12. Fenofibrate increases very low density lipoprotein triglyceride production despite reducing plasma triglyceride levels in APOE*3-Leiden.CETP mice.

    Science.gov (United States)

    Bijland, Silvia; Pieterman, Elsbet J; Maas, Annemarie C E; van der Hoorn, José W A; van Erk, Marjan J; van Klinken, Jan B; Havekes, Louis M; van Dijk, Ko Willems; Princen, Hans M G; Rensen, Patrick C N

    2010-08-13

    The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are controversial, we aimed to investigate in (more) detail the mechanism underlying the TG-lowering effect by studying VLDL-TG production and clearance using APOE*3-Leiden.CETP mice, a unique mouse model for human-like lipoprotein metabolism. Male mice were fed a Western-type diet for 4 weeks, followed by the same diet without or with fenofibrate (30 mg/kg bodyweight/day) for 4 weeks. Fenofibrate strongly lowered plasma cholesterol (-38%) and TG (-60%) caused by reduction of VLDL. Fenofibrate markedly accelerated VLDL-TG clearance, as judged from a reduced plasma half-life of glycerol tri[(3)H]oleate-labeled VLDL-like emulsion particles (-68%). This was associated with an increased post-heparin lipoprotein lipase (LPL) activity (+110%) and an increased uptake of VLDL-derived fatty acids by skeletal muscle, white adipose tissue, and liver. Concomitantly, fenofibrate markedly increased the VLDL-TG production rate (+73%) but not the VLDL-apolipoprotein B (apoB) production rate. Kinetic studies using [(3)H]palmitic acid showed that fenofibrate increased VLDL-TG production by equally increasing incorporation of re-esterified plasma fatty acids and liver TG into VLDL, which was supported by hepatic gene expression profiling data. We conclude that fenofibrate decreases plasma TG by enhancing LPL-mediated VLDL-TG clearance, which results in a compensatory increase in VLDL-TG production by the liver.

  13. Leptin induces nitric oxide-mediated inhibition of lipolysis and glyceroneogenesis in rat white adipose tissue.

    Science.gov (United States)

    Niang, Fatoumata; Benelli, Chantal; Ribière, Catherine; Collinet, Martine; Mehebik-Mojaat, Nadia; Penot, Graziella; Forest, Claude; Jaubert, Anne-Marie

    2011-01-01

    Leptin is secreted by white adipose tissue (WAT) and induces lipolysis and nonesterified fatty acid (NEFA) oxidation. During lipolysis, NEFA efflux is the result of triglyceride breakdown, NEFA oxidation, and re-esterification via glyceroneogenesis. Leptin's effects on glyceroneogenesis remain unexplored. We investigated the effect of a long-term treatment with leptin at a physiological concentration (10 μg/L) on lipolysis and glyceroneogenesis in WAT explants and analyzed the underlying mechanisms. Exposure of rat WAT explants to leptin for 2 h resulted in increased NEFA and glycerol efflux. However, a longer treatment with leptin (18 h) did not affect NEFA release and reduced glycerol output. RT-qPCR showed that leptin significantly downregulated the hormone-sensitive lipase (HSL), cytosolic phosphoenolpyruvate carboxykinase (Pck1), and PPARγ genes. In agreement with its effect on mRNA, leptin also decreased the levels of PEPCK-C and HSL proteins. Glyceroneogenesis, monitored by [1-(14) C] pyruvate incorporation into lipids, was reduced. Because leptin increases nitric oxide (NO) production in adipocytes, we explored the role of NO in the leptin signaling pathway. Pretreatment of explants with the NO synthase inhibitor Nω-nitro-l-arginine methyl ester eliminated the effect of leptin on lipolysis, glyceroneogenesis, and expression of the HSL, Pck1, and PPARγ genes. The NO donor S-nitroso-N-acetyl-DL penicillamine mimicked leptin effects, thus demonstrating the role of NO in these pathways. The inverse time-dependent action of leptin on WAT is consistent with a process that limits NEFA re-esterification and energy storage while reducing glycerol release, thus preventing hypertriglyceridemia.

  14. Uraemic sera stimulate lipolysis in human adipocytes: role of perilipin.

    Science.gov (United States)

    Axelsson, Jonas; Aström, Gaby; Sjölin, Eva; Qureshi, Abdul Rashid; Lorente-Cebrián, Silvia; Stenvinkel, Peter; Rydén, Mikael

    2011-08-01

    Although chronic kidney disease (CKD) is associated with dyslipidaemia and insulin resistance, the exact cause(s) are unknown. Since adipose tissue plays an important role in the development of these complications, we investigated the effect of uraemic sera on human adipocytes in vitro. Cultured human adipocytes were incubated for 48 h with media containing sera from eight CKD Stage 5 patients or four (matched for age, sex and body mass index) healthy controls. Glycerol release (an index of lipolysis) was determined in conditioned media. RNA was isolated from the cells and quantitative polymerase chain reaction of genes involved in lipolysis was performed. In vivo lipolysis was determined by the plasma glycerol/total fat mass (from dual energy X-ray absorptiometry) ratio in 28 CKD patients and 28 matched controls. Incubation with uraemic, but not control, sera resulted in a significant ∼30% increase in spontaneous (basal) lipolysis (P lipolysis in human adipocytes in vitro, probably by attenuating the expression of the lipolytic regulator PLIN. Since in vivo lipolysis is a well-established risk factor for insulin resistance and cardiovascular disease, these effects may promote increased morbidity and mortality in CKD.

  15. Visceral fat cell lipolysis and cardiovascular risk factors in obesity.

    Science.gov (United States)

    Andersson, D P; Löfgren, P; Thorell, A; Arner, P; Hoffstedt, J

    2011-10-01

    Visceral fat accumulation relates to cardiovascular risk factors, but the underlying mechanisms are not well understood. We investigated the role of visceral adipocyte triglyceride breakdown (lipolysis) for several risk factors of cardiovascular disease. In 73 obese women, fat mass and distribution, blood pressure, blood samples for cardiometabolic risk factors, and whole-body insulin sensitivity were determined. A subcutaneous and a visceral fat biopsy were taken. Fat cell glycerol release after stimulation with a major lipolytic hormone, noradrenaline, was measured. In simple regression analysis, visceral fat cell lipolysis, but not subcutaneous adipocyte lipolysis was related to components of the metabolic syndrome. Moreover, subjects in the highest quartile of catecholamine-induced visceral lipolysis had higher levels of systolic blood pressure, estimated liver fat, plasma levels of glucose, insulin, cholesterol, LDL-cholesterol, triglycerides and apolipoprotein B and lower whole-body insulin sensitivity than those in the lowest quartile (p=0.0004-0.048). Among subjects with the metabolic syndrome, visceral fat cell lipolysis was 40% higher than in the remaining subjects (p=0.0052). Catecholamine-activated lipolysis in visceral but not subcutaneous fat cells is associated with cardiovascular risk factors in obesity. © Georg Thieme Verlag KG Stuttgart · New York.

  16. CD36 is important for adipocyte recruitment and affects lipolysis.

    Science.gov (United States)

    Vroegrijk, Irene O C M; van Klinken, Jan Bert; van Diepen, Janna A; van den Berg, Sjoerd A A; Febbraio, Maria; Steinbusch, Laura K M; Glatz, Jan F C; Havekes, Louis M; Voshol, Peter J; Rensen, Patrick C N; van Dijk, Ko Willems; van Harmelen, Vanessa

    2013-10-01

    The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Fat cell size and number were determined in gonadal, visceral, and subcutaneous adipose tissue of CD36(-/-) and WT mice after 6 weeks on HFD. Basal lipolysis and insulin-inhibited lipolysis were investigated in gonadal adipose tissue. CD36(-/-) mice showed a reduction in adipocyte size in all fat pads. Gonadal adipose tissue also showed a lower total number of adipocytes because of a lower number of very small adipocytes (diameter lipolysis, in adipose tissue from CD36(-/-) mice, cAMP levels were increased and both basal and 8-bromo-cAMP stimulated lipolysis were higher. However, insulin-mediated inhibition of lipolysis was more potent in CD36(-/-) mice. These results indicate that during fat depot expansion, CD36-deficiency negatively affects preadipocyte recruitment and that in mature adipocytes, CD36-deficiency is associated with increased basal lipolysis and insulin responsiveness. Copyright © 2013 The Obesity Society.

  17. Biochemistry and pathophysiology of intravascular and intracellular lipolysis.

    Science.gov (United States)

    Young, Stephen G; Zechner, Rudolf

    2013-03-01

    All organisms use fatty acids (FAs) for energy substrates and as precursors for membrane and signaling lipids. The most efficient way to transport and store FAs is in the form of triglycerides (TGs); however, TGs are not capable of traversing biological membranes and therefore need to be cleaved by TG hydrolases ("lipases") before moving in or out of cells. This biochemical process is generally called "lipolysis." Intravascular lipolysis degrades lipoprotein-associated TGs to FAs for their subsequent uptake by parenchymal cells, whereas intracellular lipolysis generates FAs and glycerol for their release (in the case of white adipose tissue) or use by cells (in the case of other tissues). Although the importance of lipolysis has been recognized for decades, many of the key proteins involved in lipolysis have been uncovered only recently. Important new developments include the discovery of glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1 (GPIHBP1), the molecule that moves lipoprotein lipase from the interstitial spaces to the capillary lumen, and the discovery of adipose triglyceride lipase (ATGL) and comparative gene identification-58 (CGI-58) as crucial molecules in the hydrolysis of TGs within cells. This review summarizes current views of lipolysis and highlights the relevance of this process to human disease.

  18. Composition of human VLDL triacylglycerols after ingestion of olive oil and high oleic sunflower oil.

    Science.gov (United States)

    Ruiz-Gutiérrez, V; Morgado, N; Prada, J L; Pérez-Jiménez, F; Muriana, F J

    1998-03-01

    This work was undertaken to determine the effect of diets enriched with olive oil or high oleic sunflower oil on very low density lipoprotein (VLDL) triacylglycerol composition of healthy human subjects. Both oils contain a similar proportion of monounsaturated fatty acids (MUFA) but differ in their triacylglycerol composition. All 22 human subjects initially consumed a low fat, high carbohydrate diet as recommended by the National Cholesterol Education Program (NCEP-I). They then consumed the two experimental oils (40% dietary energy) in a crossover design. The olive oil and high oleic sunflower oil diets resulted in significant increases in palmitoleic (55%, P 100%, P sunflower oil diet increased the content of stearic acid (60%, P 100%, P sunflower oil diet). Intake of olive oil, in particular, significantly decreased the content of sn-glycerol-tripalmitate (36%, P sunflower oil diets. In addition, olive oil, but not high oleic sunflower oil, further contributed to VLDL triacylglycerols that contained alpha-linolenic and docosahexaenoic acids acylated in the sn-2 position. These data suggest that differences in the composition of VLDL triacylglycerols may be of major importance in explaining the beneficial effects of dietary olive oil in reducing the atherogenic risk profile in healthy subjects.

  19. Adipocyte pseudohypoxia suppresses lipolysis and facilitates benign adipose tissue expansion.

    Science.gov (United States)

    Michailidou, Zoi; Morton, Nicholas M; Moreno Navarrete, José Maria; West, Christopher C; Stewart, Kenneth J; Fernández-Real, José Manuel; Schofield, Christopher J; Seckl, Jonathan R; Ratcliffe, Peter J

    2015-03-01

    Prolyl hydroxylase enzymes (PHDs) sense cellular oxygen upstream of hypoxia-inducible factor (HIF) signaling, leading to HIF degradation in normoxic conditions. In this study, we demonstrate that adipose PHD2 inhibition plays a key role in the suppression of adipocyte lipolysis. Adipose Phd2 gene ablation in mice enhanced adiposity, with a parallel increase in adipose vascularization associated with reduced circulating nonesterified fatty acid levels and normal glucose homeostasis. Phd2 gene-depleted adipocytes exhibited lower basal lipolysis in normoxia and reduced β-adrenergic-stimulated lipolysis in both normoxia and hypoxia. A selective PHD inhibitor suppressed lipolysis in murine and human adipocytes in vitro and in vivo in mice. PHD2 genetic ablation and pharmacological inhibition attenuated protein levels of the key lipolytic effectors hormone-sensitive lipase and adipose triglyceride lipase (ATGL), suggesting a link between adipocyte oxygen sensing and fatty acid release. PHD2 mRNA levels correlated positively with mRNA levels of AB-hydrolase domain containing-5, an activator of ATGL, and negatively with mRNA levels of lipid droplet proteins, perilipin, and TIP47 in human subcutaneous adipose tissue. Therapeutic pseudohypoxia caused by PHD2 inhibition in adipocytes blunts lipolysis and promotes benign adipose tissue expansion and may have therapeutic applications in obesity or lipodystrophy. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. CREBH-FGF21 axis improves hepatic steatosis by suppressing adipose tissue lipolysis

    NARCIS (Netherlands)

    Park, Jong-Gil; Xu, Xu; Cho, Sungyun; Hur, Kyu Yeon; Lee, Myung-Shik; Kersten, Sander; Lee, Ann-Hwee

    2016-01-01

    Adipose tissue lipolysis produces glycerol and nonesterified fatty acids (NEFA) that serve as energy sources during nutrient scarcity. Adipose tissue lipolysis is tightly regulated and excessive lipolysis causes hepatic steatosis, as NEFA released from adipose tissue constitutes a major source of TG

  1. Laser lipolysis with a 980 nm diode laser.

    Science.gov (United States)

    Forman Taub, Amy; Friedman, Adam

    2010-05-01

    Laser lipolysis is recognized as an effective, non-surgical solution for fat removal and body reshaping. Its appeal lay in the procedure's ability to treat localized fat deposits and correct body asymmetries with apparent decreased risk compared to traditional liposuction. The energy emitted by the laser uses volumetric heating to destroy fat cells, contract skin and stimulate collagenesis. Although devices of five different wavelengths are FDA approved for lipolysis, it has been found that the 980 nm diode laser is consistently successful in inducing the required fat-heat and skin-heat interactions necessary for optimal results. Although laser lipolysis is not intended to replace traditional liposuction, it offers patients a procedure that yields similar benefits with fewer complications and faster recovery.

  2. Brain insulin controls adipose tissue lipolysis and lipogenesis.

    Science.gov (United States)

    Scherer, Thomas; O'Hare, James; Diggs-Andrews, Kelly; Schweiger, Martina; Cheng, Bob; Lindtner, Claudia; Zielinski, Elizabeth; Vempati, Prashant; Su, Kai; Dighe, Shveta; Milsom, Thomas; Puchowicz, Michelle; Scheja, Ludger; Zechner, Rudolf; Fisher, Simon J; Previs, Stephen F; Buettner, Christoph

    2011-02-02

    White adipose tissue (WAT) dysfunction plays a key role in the pathogenesis of type 2 diabetes (DM2). Unrestrained WAT lipolysis results in increased fatty acid release, leading to insulin resistance and lipotoxicity, while impaired de novo lipogenesis in WAT decreases the synthesis of insulin-sensitizing fatty acid species like palmitoleate. Here, we show that insulin infused into the mediobasal hypothalamus (MBH) of Sprague-Dawley rats increases WAT lipogenic protein expression, inactivates hormone-sensitive lipase (Hsl), and suppresses lipolysis. Conversely, mice that lack the neuronal insulin receptor exhibit unrestrained lipolysis and decreased de novo lipogenesis in WAT. Thus, brain and, in particular, hypothalamic insulin action play a pivotal role in WAT functionality. Copyright © 2011 Elsevier Inc. All rights reserved.

  3. Positional distribution of decanoic acid: Effect on chylomicron and VLDL TAG structures and postprandial lipemia

    DEFF Research Database (Denmark)

    Yli-Jokipii, K.M.; Schwab, U.S.; Tarvonen, R.L.;

    2004-01-01

    Although medium-chain FA (MCFA) are mainly absorbed via the portal venous system, they are also incorporated into chylomicron TAG; therefore, the positional distribution of MCFA in TAG is likely to affect their metabolic fate. We studied chylomicron and VLDL TAG structures, as well as the magnitu...... or in FFA concentrations. Thus, the positional distribution of MCFA in TAG affects their metabolic fate, but the magnitude of postprandial lipemia does not seem to be dependent on the positional distribution of MCFA in the ingested fat....

  4. Effects of atorvastatin and n-3 fatty acid supplementation on VLDL apolipoprotein C-III kinetics in men with abdominal obesity.

    Science.gov (United States)

    Chan, Dick C; Nguyen, Minh N; Watts, Gerald F; Ooi, Esther Mm; Barrett, P Hugh R

    2010-04-01

    Disturbed apolipoprotein (apo) C-III metabolism in obese subjects may account for hypertriglyceridemia and increased risk of cardiovascular disease. Atorvastatin and fish oils decrease plasma triglycerides and VLDL concentrations, but the underlying mechanisms are not fully understood. We studied the independent and combined effects of atorvastatin and fish oils on the metabolism of VLDL apo C-III in obese men. We carried out a 6-wk randomized, placebo-controlled, 2 x 2 factorial intervention study of atorvastatin (40 mg/d) and fish oils (4 g/d) on VLDL apo C-III kinetics in the postabsorptive state in 39 abdominally obese men using intravenous administration of d(3)-leucine. VLDL apo C-III isotopic enrichments were measured by using gas chromatography-mass spectrometry with kinetic parameters derived by using a multicompartmental model. Atorvastatin significantly (P triglycerides but did not significantly alter plasma VLDL apo C-III concentrations or kinetic parameters. Combination treatment provided no additional effect on VLDL apo C-III concentrations or kinetics compared with atorvastatin alone. In obesity, the triglyceride-lowering effect of atorvastatin, but not fish oils, is associated with increased VLDL apo C-III fractional catabolism and hence lower VLDL apo C-III concentrations. Combination treatment provided no significant additional improvement in VLDL apo C-III metabolism compared with atorvastatin alone.

  5. Tumor necrosis factor-alpha modulates human in vivo lipolysis

    DEFF Research Database (Denmark)

    Plomgaard, Peter; Fischer, Christian P; Ibfelt, Tobias;

    2008-01-01

    in lipolysis, increasing circulatory free fatty acid (FFA) levels. SUBJECTS AND METHODS: Using a randomized controlled, crossover design, healthy young male individuals (n = 10) received recombinant human (rh) TNF-alpha (700 ng/m(-2).h(-1)) for 4 h, and energy metabolism was evaluated using a combination...

  6. Fed and fasted state gastro-intestinal in vitro lipolysis

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten B; Christiansen, Martin Lau; Holm, Rene

    2014-01-01

    delivery system (SNEDDS) was either dosed in a hard gelatin capsule (SNEDDS-C) or loaded onto a porous tablet core (SNEDDS-T) and compared to a marketed conventional tablet (Conv) in an in vitro lipolysis model. The model simulates the digestion in the stomach and intestine during either the fasted...

  7. Endoplasmic reticulum stress in adipose tissue augments lipolysis.

    Science.gov (United States)

    Bogdanovic, Elena; Kraus, Nicole; Patsouris, David; Diao, Li; Wang, Vivian; Abdullahi, Abdikarim; Jeschke, Marc G

    2015-01-01

    The endoplasmic reticulum (ER) is an organelle important for protein synthesis and folding, lipid synthesis and Ca(2+) homoeostasis. Consequently, ER stress or dysfunction affects numerous cellular processes and has been implicated as a contributing factor in several pathophysiological conditions. Tunicamycin induces ER stress in various cell types in vitro as well as in vivo. In mice, a hallmark of tunicamycin administration is the development of fatty livers within 24-48 hrs accompanied by hepatic ER stress. We hypothesized that tunicamycin would induce ER stress in adipose tissue that would lead to increased lipolysis and subsequently to fatty infiltration of the liver and hepatomegaly. Our results show that intraperitoneal administration of tunicamycin rapidly induced an ER stress response in adipose tissue that correlated with increased circulating free fatty acids (FFAs) and glycerol along with decreased adipose tissue mass and lipid droplet size. Furthermore, we found that in addition to fatty infiltration of the liver as well as hepatomegaly, lipid accumulation was also present in the heart, skeletal muscle and kidney. To corroborate our findings to a clinical setting, we examined adipose tissue from burned patients where increases in lipolysis and the development of fatty livers have been well documented. We found that burned patients displayed significant ER stress within adipose tissue and that ER stress augments lipolysis in cultured human adipocytes. Our results indicate a possible role for ER stress induced lipolysis in adipose tissue as an underlying mechanism contributing to increases in circulating FFAs and fatty infiltration into other organs.

  8. Ex vivo laser lipolysis assisted with radially diffusing optical applicator

    Science.gov (United States)

    Hwang, Jieun; Hau, Nguyen Trung; Park, Sung Yeon; Rhee, Yun-Hee; Ahn, Jin-Chul; Kang, Hyun Wook

    2016-05-01

    Laser-assisted lipolysis has been implemented to reduce body fat in light of thermal interactions with adipose tissue. However, using a flat fiber with high irradiance often needs rapid cannula movements and even undesirable thermal injury due to direct tissue contact. The aim of the current study was to explore the feasibility of a radially diffusing optical applicator to liquefy the adipose tissue for effective laser lipolysis. The proposed diffuser was evaluated with a flat fiber in terms of temperature elevation and tissue liquefaction after laser lipolysis with a 980-nm wavelength. Given the same power (20 W), the diffusing applicator generated a 30% slower temperature increase with a 25% lower maximum temperature (84±3.2°C in 1 min ptissue, compared with the flat fiber. Under the equivalent temperature development, the diffuser induced up to fivefold larger area of the adipose liquefaction due to radial light emission than the flat fiber. Ex vivo tissue tests for 5-min irradiation demonstrated that the diffuser (1.24±0.15 g) liquefied 66% more adipose tissue than the flat fiber (0.75±0.05 g). The proposed diffusing applicator can be a feasible therapeutic device for laser lipolysis due to low temperature development and wide coverage of thermal treatment.

  9. Brown adipose tissue takes up plasma triglycerides mostly after lipolysis

    NARCIS (Netherlands)

    Khedoe, P.P.S.J.; Hoeke, Geerte; Kooijman, Sander; Dijk, Wieneke; Buijs, Jeroen T.; Kersten, Sander; Havekes, Louis M.; Hiemstra, Pieter S.; Berbée, Jimmy F.P.; Boon, Mariëtte R.; Rensen, Patrick C.N.

    2015-01-01

    Brown adipose tissue (BAT) produces heat by burning TGs that are stored within intracellular lipid droplets and need to be replenished by the uptake of TG-derived FA from plasma. It is currently unclear whether BAT takes up FA via uptake of TG-rich lipoproteins (TRLs), after lipolysis-mediated li

  10. Thiazolidinediones attenuate lipolysis and ameliorate dexamethasone-induced insulin resistance.

    Science.gov (United States)

    He, Jinhan; Xu, Chong; Kuang, Jiangying; Liu, Qinhui; Jiang, Hongfeng; Mo, Li; Geng, Bin; Xu, Guoheng

    2015-07-01

    Elevated levels of circulating free fatty acids induce insulin resistance and often occur in obese and diabetic conditions. One pharmacological basis for the antidiabetic effects of thiazolidinediones (TZDs) is that TZDs reduce levels of circulating FFAs by accelerating their uptake and reesterification from plasma into adipocytes. Here, we investigated whether TZDs affect adipose lipolysis, a process controlling triglyceride hydrolysis and FFA efflux to the bloodstream. The effects of TZDs on lipolysis were investigated in primary rat adipocytes in vitro and in rats in vivo. In rat primary adipocytes, the TZDs pioglitazone, rosiglitazone and troglitazone inhibited the lipolytic reaction dose- and time-dependently and in a post-receptor pathway by decreasing cAMP level and total lipase activity. TZDs increased the phosphorylation of Akt/protein kinase B, an action required for activating cyclic-nucleotide phosphodiesterase 3B, a major enzyme responsible for cAMP hydrolysis in adipocytes. Furthermore, rosiglitazone inhibited the lipolytic action in dexamethasone-stimulated adipocytes, thereby preventing the increased level of circulating FFAs, and ameliorated insulin resistance in vivo in dexamethasone-treated rats. TZDs may attenuate lipolysis and FFA efflux by activating Akt signaling to decrease cAMP level and hence reduce lipase activity in adipocytes. Inhibiting lipolysis and FFA efflux with TZDs could be a pharmacological basis by which TZDs antagonize diabetes, particularly in patients with hypercortisolemia or glucocorticoid challenge. Copyright © 2015. Published by Elsevier Inc.

  11. Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity.

    Directory of Open Access Journals (Sweden)

    Marina R Pulido

    Full Text Available Lipid droplets (LDs are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K, the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed.

  12. Rab18 dynamics in adipocytes in relation to lipogenesis, lipolysis and obesity.

    Science.gov (United States)

    Pulido, Marina R; Diaz-Ruiz, Alberto; Jiménez-Gómez, Yolanda; Garcia-Navarro, Socorro; Gracia-Navarro, Francisco; Tinahones, Francisco; López-Miranda, José; Frühbeck, Gema; Vázquez-Martínez, Rafael; Malagón, Maria M

    2011-01-01

    Lipid droplets (LDs) are organelles that coordinate lipid storage and mobilization, both processes being especially important in cells specialized in managing fat, the adipocytes. Proteomic analyses of LDs have consistently identified the small GTPase Rab18 as a component of the LD coat. However, the specific contribution of Rab18 to adipocyte function remains to be elucidated. Herein, we have analyzed Rab18 expression, intracellular localization and function in relation to the metabolic status of adipocytes. We show that Rab18 production increases during adipogenic differentiation of 3T3-L1 cells. In addition, our data show that insulin induces, via phosphatidylinositol 3-kinase (PI3K), the recruitment of Rab18 to the surface of LDs. Furthermore, Rab18 overexpression increased basal lipogenesis and Rab18 silencing impaired the lipogenic response to insulin, thereby suggesting that this GTPase promotes fat accumulation in adipocytes. On the other hand, studies of the β-adrenergic receptor agonist isoproterenol confirmed and extended previous evidence for the participation of Rab18 in lipolysis. Together, our data support the view that Rab18 is a common mediator of lipolysis and lipogenesis and suggests that the endoplasmic reticulum (ER) is the link that enables Rab18 action on these two processes. Finally, we describe, for the first time, the presence of Rab18 in human adipose tissue, wherein the expression of this GTPase exhibits sex- and depot-specific differences and is correlated to obesity. Taken together, these findings indicate that Rab18 is involved in insulin-mediated lipogenesis, as well as in β-adrenergic-induced lipolysis, likely facilitating interaction of LDs with ER membranes and the exchange of lipids between these compartments. A role for Rab18 in the regulation of adipocyte biology under both normal and pathological conditions is proposed.

  13. A review of nutritional and physiological factors affecting goat milk lipid synthesis and lipolysis.

    Science.gov (United States)

    Chilliard, Y; Ferlay, A; Rouel, J; Lamberet, G

    2003-05-01

    Although the effect of lactation stage is similar, the responses of milk yield and composition (fat and protein contents) to different types of lipid supplements differ greatly between goats and cows. Milk fat content increases with almost all studied fat supplements in goats but not in cows. However, the response of milk fatty acid (FA) composition is similar, at least for major FA, including conjugated linoleic acid (CLA) in goats and cows supplemented with either protected or unprotected lipid supplements. Goat milk CLA content increases sharply after either vegetable oil supplementation or fresh grass feeding, but does not change markedly when goats receive whole untreated oilseeds. Important interactions are observed between the nature of forages and of oil supplements on trans-10 and trans-11 C18:1 and CLA. Peculiarities of goat milk FA composition and lipolytic system play an important role in the development of either goat flavor (release of branched, medium-chain FA) or rancidity (excessive release of butyric acid). The lipoprotein lipase (LPL) activity, although lower in goat than in cow milk, is more bound to the fat globules and better correlated to spontaneous lipolysis in goat milk. The regulation of spontaneous lipolysis differs widely between goats and cows. Goat milk lipolysis and LPL activity vary considerably and in parallel across goat breeds or genotypes, and are low during early and late lactation, as well as when animals are underfed or receive a diet supplemented with protected or unprotected vegetable oils. This could contribute to decreases in the specific flavor of goat dairy products with diets rich in fat.

  14. Nutritional state modulates growth hormone-stimulated lipolysis.

    Science.gov (United States)

    Bergan, Heather E; Kittilson, Jeffrey D; Sheridan, Mark A

    2015-01-01

    Growth hormone (GH) regulates several processes in vertebrates, including two metabolically disparate processes: promotion of growth, an anabolic action, and mobilization of stored lipid, a catabolic action. In this study, we used hepatocytes isolated from continuously fed and long-term (4weeks) fasted rainbow trout (Oncorhynchus mykiss) as a model to investigate the mechanistic basis of the anabolic and catabolic actions of GH. Our hypothesis was that nutritional state modulates the lipolytic responsiveness of cells by adjusting the signal transduction pathways to which GH links. GH stimulated lipolysis as measured by increased glycerol release in both a time- and concentration-related manner from cells of fasted fish but not from cells of fed fish. Expression of mRNAs that encode the lipolytic enzyme hormone-sensitive lipase (HSL), HSL1 and HSL2, also was stimulated by GH in cells from fasted fish and not in cells from fed fish. Activation of the signaling pathways that mediate GH action also was studied. In cells from fed fish, GH activated the JAK-STAT, PI3K-Akt, and ERK pathways, whereas in cells from fasted fish, GH activated the PLC/PKC and ERK pathways. In hepatocytes from fasted fish, blockade of PLC/PKC and of the ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated HSL mRNA expression, whereas blockade of JAK-STAT or of the PI3K-Akt pathway had no effect on lipolysis or HSL expression stimulated by GH. These results indicate that during fasting GH activates the PLC/PKC and ERK pathways resulting in lipolysis but during periods of feeding GH activates a different complement of signal elements that do not promote lipolysis. These findings suggest that the responsiveness of cells to GH depends on the signal pathways to which GH links and helps resolve the growth-promoting and lipid catabolic actions of GH.

  15. Bacterial peptidoglycan stimulates adipocyte lipolysis via NOD1.

    Science.gov (United States)

    Chi, Wendy; Dao, Dyda; Lau, Trevor C; Henriksbo, Brandyn D; Cavallari, Joseph F; Foley, Kevin P; Schertzer, Jonathan D

    2014-01-01

    Obesity is associated with inflammation that can drive metabolic defects such as hyperlipidemia and insulin resistance. Specific metabolites can contribute to inflammation, but nutrient intake and obesity are also associated with altered bacterial load in metabolic tissues (i.e. metabolic endotoxemia). These bacterial cues can contribute to obesity-induced inflammation. The specific bacterial components and host receptors that underpin altered metabolic responses are emerging. We previously showed that Nucleotide-binding oligomerization domain-containing protein 1 (NOD1) activation with bacterial peptidoglycan (PGN) caused insulin resistance in mice. We now show that PGN induces cell-autonomous lipolysis in adipocytes via NOD1. Specific bacterial PGN motifs stimulated lipolysis in white adipose tissue (WAT) explants from WT, but not NOD1⁻/⁻mice. NOD1-activating PGN stimulated mitogen activated protein kinases (MAPK),protein kinase A (PKA), and NF-κB in 3T3-L1 adipocytes. The NOD1-mediated lipolysis response was partially reduced by inhibition of ERK1/2 or PKA alone, but not c-Jun N-terminal kinase (JNK). NOD1-stimulated lipolysis was partially dependent on NF-κB and was completely suppressed by inhibiting ERK1/2 and PKA simultaneously or hormone sensitive lipase (HSL). Our results demonstrate that bacterial PGN stimulates lipolysis in adipocytes by engaging a stress kinase, PKA, NF-κB-dependent lipolytic program. Bacterial NOD1 activation is positioned as a component of metabolic endotoxemia that can contribute to hyperlipidemia, systemic inflammation and insulin resistance by acting directly on adipocytes.

  16. Bacterial peptidoglycan stimulates adipocyte lipolysis via NOD1.

    Directory of Open Access Journals (Sweden)

    Wendy Chi

    Full Text Available Obesity is associated with inflammation that can drive metabolic defects such as hyperlipidemia and insulin resistance. Specific metabolites can contribute to inflammation, but nutrient intake and obesity are also associated with altered bacterial load in metabolic tissues (i.e. metabolic endotoxemia. These bacterial cues can contribute to obesity-induced inflammation. The specific bacterial components and host receptors that underpin altered metabolic responses are emerging. We previously showed that Nucleotide-binding oligomerization domain-containing protein 1 (NOD1 activation with bacterial peptidoglycan (PGN caused insulin resistance in mice. We now show that PGN induces cell-autonomous lipolysis in adipocytes via NOD1. Specific bacterial PGN motifs stimulated lipolysis in white adipose tissue (WAT explants from WT, but not NOD1⁻/⁻mice. NOD1-activating PGN stimulated mitogen activated protein kinases (MAPK,protein kinase A (PKA, and NF-κB in 3T3-L1 adipocytes. The NOD1-mediated lipolysis response was partially reduced by inhibition of ERK1/2 or PKA alone, but not c-Jun N-terminal kinase (JNK. NOD1-stimulated lipolysis was partially dependent on NF-κB and was completely suppressed by inhibiting ERK1/2 and PKA simultaneously or hormone sensitive lipase (HSL. Our results demonstrate that bacterial PGN stimulates lipolysis in adipocytes by engaging a stress kinase, PKA, NF-κB-dependent lipolytic program. Bacterial NOD1 activation is positioned as a component of metabolic endotoxemia that can contribute to hyperlipidemia, systemic inflammation and insulin resistance by acting directly on adipocytes.

  17. Increased hepatic VLDL secretion, lipogenesis, and SREBP-1 expression in the corpulent JCR:LA-cp rat.

    Science.gov (United States)

    Elam, M B; Wilcox, H G; Cagen, L M; Deng, X; Raghow, R; Kumar, P; Heimberg, M; Russell, J C

    2001-12-01

    The corpulent JCR:LA-cp rat (cp/cp) is a useful model for study of the metabolic consequences of obesity and hyperinsulinemia. To assess the effect of hyperinsulinemia on VLDL secretion in this model, we measured rates of secretion of VLDL in perfused livers derived from cp/cp rats and their lean littermates. Livers of cp/cp rats secreted significantly greater amounts of VLDL triglyceride and apolipoprotein, compared with lean littermates. The content of apoB, apoE, and apoCs in both perfusate and plasma VLDL was greater in the cp/cp rat, as was the apolipoprotein (apo)C, apoA-I, and apoA-IV content of plasma HDL. Triglyceride content was also greater in cp/cp livers, as was hepatic lipogenesis and expression of lipogenic enzymes and sterol regulatory element binding protein-1 (SREBP-1). Hepatic mRNAs for apoE, and apoA-I were higher in livers of cp/cp rats. In contrast, the steady state levels of apoC-II, apoC-III, and apoB mRNAs were unchanged. Thus, livers of obese hyperinsulinemic cp/cp JCR:LA-cp rats secrete a greater number of VLDL particles that are enriched in triglyceride, apoE, and apoC. Greater secretion of VLDL in the cp/cp rat in part results from higher endogenous fatty acid synthesis, which in turn may occur in response to increased expression of the lipogenic enzyme regulator SREBP-1c.

  18. Regulation of lipolysis in small and large fat cells of the same subject.

    Science.gov (United States)

    Laurencikiene, Jurga; Skurk, Thomas; Kulyté, Agné; Hedén, Per; Aström, Gaby; Sjölin, Eva; Rydén, Mikael; Hauner, Hans; Arner, Peter

    2011-12-01

    Large fat cell size is linked to type 2 diabetes risk and may involve an enhanced rate of adipocyte lipolysis causing elevated levels of fatty acids. Our objective was to study the role of fat cell size in the regulation of lipolysis within a subject. Subcutaneous adipose tissue was obtained from 16 healthy subjects. Large and small adipocytes were isolated for each sample. Hormonal regulation of lipolysis and expression of lipolysis-regulating proteins were investigated. No effect of cell size on the rate of lipolysis was observed when lipolysis was expressed per lipid weight of fat cells. However, when expressed per number of fat cells, the lipolysis was significantly higher in large as compared with small adipocytes. This was observed in both the unstimulated (basal) state and in the presence of the major lipolysis-regulating hormones such as catecholamines (stimulating), natriuretic peptides (stimulating), and insulin (inhibiting). The receptor properties (number, affinity, and coupling) for these hormones did not differ between large and small adipocytes. However, the expression of proteins regulating the final steps in hormone signaling to lipolysis (hormone-sensitive lipase, adipose triglyceride lipase, and perilipin) was increased in large adipocytes. Independently of the donor, sc fat cell size per se determines lipolysis rates. Large adipocytes have increased lipolytic capacity, probably due to the enrichment of regulatory proteins distal in the lipolytic cascade, to which all lipolytic signals converge (lipases and perilipin). Enhanced lipolytic capacity may link adipocyte hypertrophy to the risk of developing type 2 diabetes.

  19. [Physiological and pathophysiological features of the control of lipolysis and lipid mobilization by natriuretic peptides].

    Science.gov (United States)

    Moro, Cédric; Berlan, Michel; Lafontan, Max

    2006-01-01

    We have demonstrated a potent and specific lipolytic effect of natriuretic peptides (NP) in human and primates' fat cells. The lipolytic effect of NP is mediated through intracellular production of cGMP and activation of the cGMP-dependent kinase 1alpha. Local infusion of atrial-NP (ANP), directly within the subcutaneous adipose tissue through a microdialysis catheter, increases lipolysis and stimulates blood flow through its vasodilating effect in lean healthy men. This effect is blunted in overweight men and can be recovered by endurance training. Intravenous infusion of physiological doses of ANP induces lipid mobilization. Higher concentrations of ANP that are encountered during heart failure also stimulate lipid oxidation. ANP activates lipolysis and free fatty acids release from adipose tissue during endurance exercise. This effect is paradoxically amplified when exercise is performed under beta-blockade treatment, because of an enhanced cardiac release of ANP. No gender differences in ANP-induced lipid mobilization during exercise have been found. Heart failure is associated with high circulating levels of NP that could participate to the progression toward cachexia. On contrary, a negative correlation between NP levels and body mass index is found in obese persons. The molecular basis of this inverse correlation is not yet demonstrated from a functional standpoint. Further studies are needed to clearly define the pathophysiological role of NP in obesity and heart failure.

  20. Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

    Directory of Open Access Journals (Sweden)

    Stephanie M Marshall

    Full Text Available An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL support TICE, antisense oligonucleotides (ASO were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP, which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg mice, which predominantly excrete cholesterol via TICE, and wild type (WT littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

  1. Lipoprotein lipase S447X variant associated with VLDL, LDL and HDL diameter clustering in the MetS

    Science.gov (United States)

    Previous analysis clustered 1,238 individuals from the general population Genetics of Lipid Lowering Drugs Network (GOLDN) study by the size of their fasting very low-density, low-density and high-density lipoproteins (VLDL, LDL, HDL) using latent class analysis. From two of the eight identified gro...

  2. Effects of dietary fish oil on serum lipids and VLDL kinetics in hyperlipidemic apolipoprotein E*3-Leiden transgenic mice

    NARCIS (Netherlands)

    Vlijmen, B.J.M. van; Mensink, R.P.; Hof, H.B. van 't; Offermans, R.F.G.; Hofker, M.H.; Havekes, L.M.

    1998-01-01

    Studying the effects of dietary fish oil on VLDL metabolism in humans is subject to both large intra- and interindividual variability. In the present study we therefore used hyperlipidentic apolipoprotein (APO) E*3-Leiden mice, which have impaired chylomicron and very low density lipoprotein (VDL) r

  3. Increased VLDL in nephrotic patients results from a decreased catabolism while increased LDL results from increased synthesis

    NARCIS (Netherlands)

    de Sain-van der Velden, M; Kaysen, GA; Barrett, HA; Stellaard, F; Gadellaa, MM; Voorbij, HA; Reijngoud, DJ; Rabelink, TJ

    1998-01-01

    Increased very low density lipoprotein (VLDL) in nephrotic patients results from a decreased catabolism while increased low density lipoprotein (LDL) results from increased synthesis. Hyperlipidemias a hallmark of nephrotic syndrome that has been associated with increased risk for ischemic heart dis

  4. Reduction of VLDL secretion decreases cholesterol excretion in niemann-pick C1-like 1 hepatic transgenic mice.

    Science.gov (United States)

    Marshall, Stephanie M; Kelley, Kathryn L; Davis, Matthew A; Wilson, Martha D; McDaniel, Allison L; Lee, Richard G; Crooke, Rosanne M; Graham, Mark J; Rudel, Lawrence L; Brown, J Mark; Temel, Ryan E

    2014-01-01

    An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high cholesterol diet, Niemann-Pick C1-like 1 hepatic transgenic (L1Tg) mice, which predominantly excrete cholesterol via TICE, and wild type (WT) littermates were treated with control ASO or MTP ASO. In both WT and L1Tg mice, MTP ASO decreased VLDL triglyceride (TG) and cholesterol secretion. Regardless of treatment, L1Tg mice had reduced biliary cholesterol compared to WT mice. However, only L1Tg mice treated with MTP ASO had reduced fecal cholesterol excretion. Based upon these findings, we conclude that VLDL or a byproduct such as LDL can move cholesterol from the liver to the small intestine for TICE.

  5. MRI demonstration of orbital lipolysis in anorexia nervosa

    Energy Technology Data Exchange (ETDEWEB)

    Demaerel, Philippe; Dekimpe, Piet; Wilms, Guy [Department of Radiology, University Hospitals, Herestraat 49, 3000 Leuven (Belgium); Muls, Erik [Department of Endocrinology, University Hospitals, Herestraat 49, 3000 Leuven (Belgium)

    2002-07-01

    The purpose of this article is to describe the orbital changes due to lipolysis in anorexia nervosa. We examined a cachectic patient with MR imaging using T1-weighted images before and after contrast enhancement. Orbital fat edema has been observed in extreme forms of cachexia and the CT and MR findings have recently been reported. The imaging appearances have been explained by the disappearance of the fat tissue and the appearance of edema due to a disturbance in the electrolyte fluid balance. In the recent literature particular attention has been paid to the increased lipid peroxidation and lipolysis in anorexia nervosa. These metabolic processes result in an increased permeability of the vessel wall endothelium, which can explain the extravasation of the contrast agent in the orbital fat on MR imaging. (orig.)

  6. FAT FLUX: enzymes, regulators, and pathophysiology of intracellular lipolysis.

    Science.gov (United States)

    Zechner, Rudolf

    2015-04-01

    The great 19(th) century French physiologist Claude Bernard reasoned "Man can learn nothing except by going from the known to the unknown". This premise is particularly applicable to the progression of discoveries made in the field of fat metabolism since Bernard's time. Beginning with his groundbreaking discovery of fat digestion (later termed "lipolysis") in 1848, research addressing the basic processes of cellular storage and mobilization of fat has steadily advanced. Even after 150 years of research dedicated to lipolysis, exciting new principles have continued to emerge in the last 10 years. This Perspective summarizes these recent landmark discoveries in the field and emphasizes their relevance for the pathogenesis of extremely prevalent diseases such as obesity, heart disease, and cancer.

  7. Laser lipolysis versus traditional liposuction for fat removal.

    Science.gov (United States)

    Mordon, Serge; Plot, Eric

    2009-11-01

    Liposuction is second only to breast augmentation as the most commonly performed cosmetic procedure in the USA. Liposuction removes fat through very small skin incisions, with atraumatic, blunt-tipped cannulas. Simplicity, quality of results and relatively rare complications are but a few benefits that explain its success. Its main limitation is the minimal skin retraction achieved after the procedure. Laser lipolysis is based on a thermal effect. The laser can vaporize, melt tissues and coagulate blood vessels. More importantly, the laser stimulates the formation of collagen in the region, enhancing skin elasticity and promoting skin contraction in the treated areas. This review aims to describe traditional liposuction and laser lipolysis, and discusses the difference between the two techniques.

  8. Germline ablation of VGF increases lipolysis in white adipose tissue.

    Science.gov (United States)

    Fargali, Samira; Scherer, Thomas; Shin, Andrew C; Sadahiro, Masato; Buettner, Christoph; Salton, Stephen R

    2012-11-01

    Targeted deletion of VGF, a neuronal and endocrine secreted protein and neuropeptide precursor, produces a lean, hypermetabolic mouse that is resistant to diet-, lesion-, and genetically induced obesity and diabetes. We hypothesized that increased sympathetic nervous system activity in Vgf-/Vgf- knockout mice is responsible for increased energy expenditure and decreased fat storage and that increased β-adrenergic receptor stimulation induces lipolysis in white adipose tissue (WAT) of Vgf-/Vgf- mice. We found that fat mass was markedly reduced in Vgf-/Vgf- mice. Within knockout WAT, phosphorylation of protein kinase A substrate increased in males and females, phosphorylation of hormone-sensitive lipase (HSL) (ser563) increased in females, and levels of adipose triglyceride lipase, comparative gene identification-58, and phospho-perilipin were higher in male Vgf-/Vgf- WAT compared with wild-type, consistent with increased lipolysis. The phosphorylation of AMP-activated protein kinase (AMPK) (Thr172) and levels of the AMPK kinase, transforming growth factor β-activated kinase 1, were decreased. This was associated with a decrease in HSL ser565 phosphorylation, the site phosphorylated by AMPK, in both male and female Vgf-/Vgf- WAT. No significant differences in phosphorylation of CREB or the p42/44 MAPK were noted. Despite this evidence supporting increased cAMP signaling and lipolysis, lipogenesis as assessed by fatty acid synthase protein expression and phosphorylated acetyl-CoA carboxylase was not decreased. Our data suggest that the VGF precursor or selected VGF-derived peptides dampen sympathetic outflow pathway activity to WAT to regulate fat storage and lipolysis.

  9. Polycystic ovary syndrome : A study of adipocyte lipolysis in relation to endocrine and metabolic status

    OpenAIRE

    Ek, Ingvar

    2003-01-01

    The aim of the present thesis was to obtain insight into possible regulatory effects of androgens on the regulation of lipolysis in subcutaneous as well as visceral adipose tissue in women with the polycystic ovary syndrome (PCOS). In nonobese women with PCOS, adrenergic lipolysis was investigated in both subcutaneous abdominal and visceral adipose tissue and several, novel disturbances were found. In subcutaneous adipose tissue, there was a markedly impaired lipolysis,...

  10. Insulin Regulates Adipocyte Lipolysis via an Akt-Independent Signaling Pathway ▿

    OpenAIRE

    Choi, Sarah M.; Tucker, David F.; Gross, Danielle N.; Easton, Rachael M.; DiPilato, Lisa M.; Dean, Abigail S.; Monks, Bob R.; Birnbaum, Morris J.

    2010-01-01

    After a meal, insulin suppresses lipolysis through the activation of its downstream kinase, Akt, resulting in the inhibition of protein kinase A (PKA), the main positive effector of lipolysis. During insulin resistance, this process is ineffective, leading to a characteristic dyslipidemia and the worsening of impaired insulin action and obesity. Here, we describe a noncanonical Akt-independent, phosphoinositide-3 kinase (PI3K)-dependent pathway that regulates adipocyte lipolysis using restric...

  11. Suppression of adipose lipolysis by long-chain fatty acid analogs.

    Science.gov (United States)

    Kalderon, Bella; Azazmeh, Narmen; Azulay, Nili; Vissler, Noam; Valitsky, Michael; Bar-Tana, Jacob

    2012-05-01

    Agonist-induced lipolysis of adipose fat is robustly inhibited by insulin or by feedback inhibition by the long-chain fatty acids (LCFA) produced during lipolysis. However, the mode of action of LCFA in suppressing adipose lipolysis is not clear. β,β'-Tetramethyl hexadecanedioic acid (Mββ/ EDICA16) is a synthetic LCFA that is neither esterified into lipids nor β-oxidized, and therefore, it was exploited for suppressing agonist-induced lipolysis in analogy to natural LCFA. Mββ is shown here to suppress isoproterenol-induced lipolysis in the rat in vivo as well as in 3T3-L1 adipocytes. Inhibition of isoproterenol-induced lipolysis is due to decrease in isoproterenol-induced cAMP with concomitant inhibition of the phosphorylation of hormone-sensitive lipase and perilipin by protein kinase A. Suppression of cellular cAMP levels is accounted for by inhibition of the adenylate cyclase due to suppression of Raf1 expression by Mββ-activated AMPK. Suppression of Raf1 is further complemented by induction of components of the unfolded-protein-response by Mββ. Our findings imply genuine inhibition of agonist-induced adipose lipolysis by LCFA, independent of their β-oxidation or reesterification. Mββ suppression of agonist-induced lipolysis and cellular cAMP levels independent of the insulin transduction pathway may indicate that synthetic LCFA could serve as insulin mimetics in the lipolysis context under conditions of insulin resistance.

  12. PPARgamma agonism increases rat adipose tissue lipolysis, expression of glyceride lipases, and the response of lipolysis to hormonal control.

    Science.gov (United States)

    Festuccia, W T; Laplante, M; Berthiaume, M; Gélinas, Y; Deshaies, Y

    2006-10-01

    The aim of this study was to investigate the effect and mechanisms of action of in vivo peroxisome proliferator-activated receptor gamma (PPARgamma) activation on white adipose tissue (WAT) lipolysis and NEFA metabolism. Study rats were treated for 7 days with 15 mg/kg of rosiglitazone per day; control rats were not treated. After a 6-h fast, lipolysis and levels of mRNA for lipases were assessed in explants from various adipose depots. Rosiglitazone markedly increased basal and noradrenaline (norepinephrine)-stimulated glycerol and NEFA release from WAT explants, and amplified their inhibition by insulin. Primary adipocytes isolated from PPARgamma agonist-treated rats were also more responsive to noradrenaline stimulation expressed per cell, ruling out a contribution of an altered number of mature adipocytes in explants. Rosiglitazone concomitantly increased levels of mRNA transcripts for adipose triglyceride lipase (ATGL) and monoglyceride lipase (MGL) in subcutaneous and visceral WAT, and mRNA for hormone-sensitive lipase (HSL) in subcutaneous WAT. Lipase expression increased within 12 h of in vitro exposure of naïve explants to rosiglitazone, suggesting direct transcriptional activation. In parallel, chronic in vivo treatment with rosiglitazone lowered plasma NEFAs and in WAT its expected stimulatory action on glycerol and NEFA recycling, and on the expression of genes involved in NEFA uptake and retention by WAT, such processes counteracting net NEFA export. These findings demonstrate that, in the face of its plasma NEFA-lowering action, PPARgamma agonism stimulates WAT lipolysis, an effect that is compensated by lipid-retaining pathways. The results further suggest that PPARgamma agonism stimulates lipolysis by increasing the lipolytic potential, including the expression levels of the genes encoding adipose triglyceride lipase and monoglyceride lipase.

  13. A dynamic in vitro lipolysis model. I. Controlling the rate of lipolysis by continuous addition of calcium.

    Science.gov (United States)

    Zangenberg, N H; Müllertz, A; Kristensen, H G; Hovgaard, L

    2001-09-01

    Lipolysis by pancreatic lipase was investigated with the aim to establish an in vitro lipolysis model, which can be used to investigate the dissolution of poorly soluble lipophilic drug substances at controlled hydrolysis rates. The effects of three experimental parameters -- the concentrations of bile salts and Ca(2+) and the lipase activity -- were investigated. The effect on the rate of hydrolysis of emulsified soybean oil was investigated in experiments in a pH-stat at pH 6.5 and 37 degrees C. The free fatty acids produced by the hydrolysis were titrated at pH 6.5. It was shown that all three investigated parameters influence the initial rate of hydrolysis, whereas only the lipase activity and the concentration of Ca(2+) affect the subsequent stages. It was also shown that the rate of lipolysis can be controlled by the rate of adding Ca(2+). Thus, it is possible to design an in vitro model using readily available and inexpensive materials in which the hydrolysis rate can be controlled by the continuous addition of Ca(2+).

  14. Amino acid-sensing mTOR signaling is involved in modulation of lipolysis by chronic insulin treatment in adipocytes

    OpenAIRE

    Zhang, Chongben; Yoon, Mee-Sup; Chen, Jie

    2009-01-01

    Chronically high insulin levels and increased circulating free fatty acids released from adipose tissue through lipolysis are two features associated with insulin resistance. The relationship between chronic insulin exposure and adipocyte lipolysis has been unclear. In the present study we found that chronic insulin exposure in 3T3-L1 adipocytes, as well as in mouse primary adipocytes, increased basal lipolysis rates. This effect of insulin on lipolysis was only observed when the mammalian ta...

  15. The VLDL receptor promotes lipotoxicity and increases mortality in mice following an acute myocardial infarction

    Science.gov (United States)

    Perman, Jeanna C.; Boström, Pontus; Lindbom, Malin; Lidberg, Ulf; StÅhlman, Marcus; Hägg, Daniel; Lindskog, Henrik; Scharin Täng, Margareta; Omerovic, Elmir; Mattsson Hultén, Lillemor; Jeppsson, Anders; Petursson, Petur; Herlitz, Johan; Olivecrona, Gunilla; Strickland, Dudley K.; Ekroos, Kim; Olofsson, Sven-Olof; Borén, Jan

    2011-01-01

    Impaired cardiac function is associated with myocardial triglyceride accumulation, but it is not clear how the lipids accumulate or whether this accumulation is detrimental. Here we show that hypoxia/ischemia-induced accumulation of lipids in HL-1 cardiomyocytes and mouse hearts is dependent on expression of the VLDL receptor (VLDLR). Hypoxia-induced VLDLR expression in HL-1 cells was dependent on HIF-1α through its interaction with a hypoxia-responsive element in the Vldlr promoter, and VLDLR promoted the endocytosis of lipoproteins. Furthermore, VLDLR expression was higher in ischemic compared with nonischemic left ventricles from human hearts and was correlated with the total lipid droplet area in the cardiomyocytes. Importantly, Vldlr–/– mice showed improved survival and decreased infarct area following an induced myocardial infarction. ER stress, which leads to apoptosis, is known to be involved in ischemic heart disease. We found that ischemia-induced ER stress and apoptosis in mouse hearts were reduced in Vldlr–/– mice and in mice treated with antibodies specific for VLDLR. These findings suggest that VLDLR-induced lipid accumulation in the ischemic heart worsens survival by increasing ER stress and apoptosis. PMID:21670500

  16. ADP-ribosylation factor 6 regulates endothelin-1-induced lipolysis in adipocytes.

    Science.gov (United States)

    Davies, Jonathon C B; Bain, Stephen C; Kanamarlapudi, Venkateswarlu

    2014-08-15

    Endothelin-1 (ET-1) induces lipolysis in adipocytes, where ET-1 chronic exposure results in insulin resistance (IR) through suppression of glucose transporter (GLUT)4 translocation to the plasma membrane and consequently glucose uptake. ARF6 small GTPase, which plays a vital role in cell surface receptors trafficking, has previously been shown to regulate GLUT4 recycling and thereby insulin signalling. ARF6 also plays a role in ET-1 promoted endothelial cell migration. However, ARF6 involvement in ET-1-induced lipolysis in adipocytes is unknown. Therefore, we investigated the role of ARF6 in ET-1-induced lipolysis in 3T3-L1 adipocytes. This was achieved by studying the effect of inhibitors for the activation of ARF6 and other signalling proteins on ET-1 induced lipolysis and ARF6 activation in the adipocytes. Our results indicate that ET-1 induces, through endothelin type A receptor (ETAR), lipolysis, the ARF6 activation and extracellular-signal regulated kinase (ERK) phosphorylation in adipocytes, further ET-1 stimulated lipolysis is inhibited by the inhibitors of ARF6 activation, ERK phosphorylation and dynamin, which is essential for endocytosis. Our studies also revealed that ARF6 acts upstream of ERK in ET-1-indcued lipolysis. In summary, we determined that ET-1 activation of ETAR signalled through ARF6, which is crucial for lipolysis. Copyright © 2014 Elsevier Inc. All rights reserved.

  17. Perilipin Promotes HSL-Mediated Adipocyte Lipolysis via Phosphorylation-dependent and Independent Mechanisms

    Science.gov (United States)

    Hormone-sensitive lipase (HSL) is the predominant lipase effector of catecholamine-stimulated lipolysis in adipocytes. HSL-dependent lipolysis, in response to catecholamines, is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin A (Peri A), an essential lipid droplet (LD)-ass...

  18. The role of mouse Akt2 in insulin-dependent suppression of adipocyte lipolysis in vivo

    Science.gov (United States)

    Koren, Shlomit; DiPilato, Lisa M.; Emmett, Matthew J.; Shearin, Abigail L.; Chu, Qingwei; Monks, Bob; Birnbaum, Morris J.

    2015-01-01

    Aim/hypothesis The release of fatty acids from adipocytes, i.e. lipolysis, is maintained under tight control, primarily by the opposing actions of catecholamines and insulin. A widely accepted model is that insulin antagonises catecholamine-dependent lipolysis through phosphorylation and activation of cAMP phosphodiesterase 3B (PDE3B) by the serine-threonine protein kinase Akt (protein kinase B). Recently, this hypothesis has been challenged, as in cultured adipocytes insulin appears, under some conditions, to suppress lipolysis independently of Akt. Methods To address the requirement for Akt2, the predominant isoform expressed in classic insulin target tissues, in the suppression of fatty acid release in vivo, we assessed lipolysis in mice lacking Akt2. Results In the fed state and following an oral glucose challenge, Akt2 null mice were glucose intolerant and hyperinsulinaemic, but nonetheless exhibited normal serum NEFA and glycerol levels, suggestive of normal suppression of lipolysis. Furthermore, insulin partially inhibited lipolysis in Akt2 null mice during an insulin tolerance test (ITT) and hyperinsulinaemic–euglycaemic clamp, respectively. In support of these in vivo observations, insulin antagonised catecholamine-induced lipolysis in primary brown fat adipocytes from Akt2-deficient nice. Conclusion These data suggest that suppression of lipolysis by insulin in hyperinsulinaemic states can take place in the absence of Akt2. PMID:25740694

  19. Effects of Genetic Loci Associated with Central Obesity on Adipocyte Lipolysis.

    Science.gov (United States)

    Strawbridge, Rona J; Laumen, Helmut; Hamsten, Anders; Breier, Michaela; Grallert, Harald; Hauner, Hans; Arner, Peter; Dahlman, Ingrid

    2016-01-01

    Numerous genetic loci have been associated with measures of central fat accumulation, such as waist-to-hip ratio adjusted for body mass index (WHRadjBMI). However the mechanisms by which genetic variations influence obesity remain largely elusive. Lipolysis is a key process for regulation of lipid storage in adipocytes, thus is implicated in obesity and its metabolic complications. Here, genetic variants at 36 WHRadjBMI-associated loci were examined for their influence on abdominal subcutaneous adipocyte lipolysis. Fasting subcutaneous adipose tissue biopsies were collected from 789 volunteers (587 women and 202 men, body mass index (BMI) range 17.7-62.3 kg/m2). We quantified subcutaneous adipocyte lipolysis, both spontaneous and stimulated by the catecholamine isoprenaline or a cyclic AMP analogue. DNA was extracted from peripheral blood mononuclear cells and genotyping of SNPs associated with WHRadjBMI conducted. The effects on adipocyte lipolysis measures were assessed for SNPs individually and combined in a SNP score. The WHRadjBMI-associated loci CMIP, PLXND1, VEGFA and ZNRF3-KREMEN1 demonstrated nominal associations with spontaneous and/or stimulated lipolysis. Candidate genes in these loci have been reported to influence NFκB-signaling, fat cell size and Wnt signalling, all of which may influence lipolysis. This report provides evidence for specific WHRadjBMI-associated loci as candidates to modulate adipocyte lipolysis. Additionally, our data suggests that genetically increased central fat accumulation is unlikely to be a major cause of altered lipolysis in abdominal adipocytes.

  20. Adipose tissue mitochondrial respiration and lipolysis before and after a weight loss by diet and RYGB.

    Science.gov (United States)

    Hansen, Merethe; Lund, Michael T; Gregers, Emilie; Kraunsøe, Regitze; Van Hall, Gerrit; Helge, Jørn W; Dela, Flemming

    2015-10-01

    To study adipose tissue mitochondrial respiration and lipolysis following a massive weight loss. High resolution respirometry of adipose tissue biopsies and tracer determined whole body lipolysis. Sixteen obese patients with type 2 diabetes (T2DM) and 27 without (OB) were studied following a massive weight loss by diet and Roux-en-Y gastric bypass (RYGB). The mitochondrial respiratory rates were similar in OB and T2DM, and the mass-specific oxygen flux increased significantly 4 and 18 months post-surgery (P Lipolysis per fat mass was similar in the two groups and was increased (P Lipolysis increases in the short term post-surgery, and insulin sensitivity for suppression of lipolysis increases with RYGB. © 2015 The Obesity Society.

  1. Interactions of Apolipoproteins AI, AII, B and HDL, LDL, VLDL with Polyurethane and Polyurethane-PEO Surfaces.

    Science.gov (United States)

    Cornelius, R M; Macri, J; Cornelius, K M; Brash, J L

    2015-11-10

    The lipoproteins (HDL, LDL, VLDL) are important components of blood present in high concentration. Surprisingly, their role in blood-biomaterial interactions has been largely ignored. In previous work apolipoprotein AI (the main protein component of HDL) was identified as a major constituent of protein layers adsorbed from plasma to biomaterials having a wide range of surface properties, and quantitative data on the adsorption of apo AI to a biomedical grade polyurethane were reported. In the present communication quantitative data on the adsorption of apo AI, apo AII and apoB (the latter being a constituent of LDL and VLDL), as well as the lipoprotein particles themselves (HDL, LDL, VLDL), to a biomedical segmented polyurethane (PU) with and without an additive containing poly(ethylene oxide) (material referred to as PEO) are reported. Using radiolabeled apo AI, apo AII, and apoB, adsorption levels on PU from buffer at a protein concentration of 50 μg/mL were found to be 0.34, 0.40, and 0.14 μg/cm(2) (12, 23, and 0.25 nmol/cm(2)) respectively. Adsorption to the PEO surface was PEO as well as to the PU surface. X-ray photoelectron spectra, following exposure of the surfaces to the lipoproteins, showed a strong phosphorus signal, confirming that adsorption had occurred. It therefore appears that a PEO-containing surface that is resistant to apolipoproteins may be less resistant to the corresponding lipoproteins.

  2. Increased lipolysis and energy expenditure in a mouse model with severely impaired glucagon secretion.

    Directory of Open Access Journals (Sweden)

    Phing-How Lou

    Full Text Available BACKGROUND: Secretion of insulin and glucagon is triggered by elevated intracellular calcium levels. Although the precise mechanism by which the calcium signal is coupled to insulin and glucagon granule exocytosis is unclear, synaptotagmin-7 has been shown to be a positive regulator of calcium-dependent insulin and glucagon secretion, and may function as a calcium sensor for insulin and glucagon granule exocytosis. Deletion of synaptotagmin-7 leads to impaired glucose-stimulated insulin secretion and nearly abolished Ca(2+-dependent glucagon secretion in mice. Under non-stressed resting state, however, synaptotagmin-7 KO mice exhibit normal insulin level but severely reduced glucagon level. METHODOLOGY/PRINCIPAL FINDINGS: We studied energy expenditure and metabolism in synaptotagmin-7 KO and control mice using indirect calorimetry and biochemical techniques. Synaptotagmin-7 KO mice had lower body weight and body fat content, and exhibited higher oxygen consumption and basal metabolic rate. Respiratory exchange ratio (RER was lower in synaptotagmin-7 KO mice, suggesting an increased use of lipid in their energy production. Consistent with lower RER, gene expression profiles suggest enhanced lipolysis and increased capacity for fatty acid transport and oxidation in synaptotagmin-7 KO mice. Furthermore, expression of uncoupling protein 3 (UCP3 in skeletal muscle was approximately doubled in the KO mice compared with control mice. CONCLUSIONS: These results show that the lean phenotype in synaptotagmin-7 KO mice was mostly attributed to increased lipolysis and energy expenditure, and suggest that reduced glucagon level may have broad influence on the overall metabolism in the mouse model.

  3. Effects of Epigallocatechin-3-Gallate on Autophagic Lipolysis in Adipocytes

    Directory of Open Access Journals (Sweden)

    Sang-Nam Kim

    2017-06-01

    Full Text Available Previous studies demonstrated effects of green tea on weight loss; however, green tea-induced modulation of adipocyte function is not fully understood. Here, we investigated effects of the major green tea phytochemical, epigallocatechin-3-gallate (EGCG on triglyceride contents, lipolysis, mitochondrial function, and autophagy, in adipocytes differentiated from C3H10T1/2 cells and immortalized pre-adipocytes in vitro. EGCG reduced the triglycerol content significantly in adipocytes by 25%, comparable to the nutrient starvation state. EGCG did not affect protein kinase A signaling or brown adipocyte marker expression in adipocytes; however, EGCG increased autophagy, as measured by autophagy flux analysis and immunoblot analysis of LC3B, ATG7, and Beclin1. EGCG treatment reduced mitochondrial membrane potential by 56.8% and intracellular ATP levels by 49.1% compared to controls. Although mammalian target of rapamycin signaling was not upregulated by EGCG treatment, EGCG treatment induced AMP-activated protein kinase phosphorylation, indicating an energy-depleted state. In addition, EGCG increased the association between RAB7 and lipid droplets, suggesting that lipophagy was activated. Finally, knockdown of Rab7 attenuated the EGCG-dependent reduction in lipid contents. Collectively, these results indicated that EGCG upregulated autophagic lipolysis in adipocytes, supporting the therapeutic potential of EGCG as a caloric restriction mimetic to prevent obesity and obesity-related metabolic diseases.

  4. Effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in adipocytes.

    Science.gov (United States)

    Kim, Hye-Kyeong; Della-Fera, Mary Anne; Hausman, Dorothy B; Baile, Clifton A

    2010-09-01

    Clenbuterol, a beta(2)-adrenergic receptor (beta(2)-AR) selective agonist, has been shown to decrease body fat in animals and can induce apoptosis in adipose tissue in mice. We hypothesized that direct actions of a beta-adrenergic receptor agonist on adipocytes could trigger the observed apoptotic effect. The hypothesis was inspected by investigating the direct effect of clenbuterol on apoptosis, adipogenesis, and lipolysis in vitro using the 3T3-L1 cell line and rat primary adipocytes. Cells were treated with 10(-9) to 10(-5) M clenbuterol depending on the experiments. There was no apoptotic effect of clenbuterol both in 3T3-L1 cells and rat primary adipocytes. Adipogenesis monitored by Oil Red O staining and AdipoRed assay was modestly decreased by clenbuterol treatment (p < 0.05). In fully differentiated primary adipocytes, clenbuterol increased basal lipolysis compared with the control (p < 0.01). In summary, direct stimulation of beta(2)-AR by clenbuterol does not cause apoptosis in adipocytes, despite a direct lipolytic stimulation and attenuation of adipogenesis.

  5. Sympathetic neuro-adipose connections mediate leptin-driven lipolysis.

    Science.gov (United States)

    Zeng, Wenwen; Pirzgalska, Roksana M; Pereira, Mafalda M A; Kubasova, Nadiya; Barateiro, Andreia; Seixas, Elsa; Lu, Yi-Hsueh; Kozlova, Albina; Voss, Henning; Martins, Gabriel G; Friedman, Jeffrey M; Domingos, Ana I

    2015-09-24

    Leptin is a hormone produced by the adipose tissue that acts in the brain, stimulating white fat breakdown. We find that the lipolytic effect of leptin is mediated through the action of sympathetic nerve fibers that innervate the adipose tissue. Using intravital two-photon microscopy, we observe that sympathetic nerve fibers establish neuro-adipose junctions, directly "enveloping" adipocytes. Local optogenetic stimulation of sympathetic inputs induces a local lipolytic response and depletion of white adipose mass. Conversely, genetic ablation of sympathetic inputs onto fat pads blocks leptin-stimulated phosphorylation of hormone-sensitive lipase and consequent lipolysis, as do knockouts of dopamine β-hydroxylase, an enzyme required for catecholamine synthesis. Thus, neuro-adipose junctions are necessary and sufficient for the induction of lipolysis in white adipose tissue and are an efferent effector of leptin action. Direct activation of sympathetic inputs to adipose tissues may represent an alternative approach to induce fat loss, circumventing central leptin resistance. PAPERCLIP. Copyright © 2015 Elsevier Inc. All rights reserved.

  6. Fenofibrate increases very low density lipoprotein triglyceride production despite reducing plasma triglyceride levels in APOE*3-Leiden.CETP mice

    NARCIS (Netherlands)

    Bijland, S.; Pieterman, E.J.; Maas, A.C.E.; Hoorn, J.W.A. van der; Erk, M.J. van; Klinken, J.B. van; Havekes, L.M.; Dijk, K.W. van; Princen, H.M.G.; Rensen, P.C.N.

    2010-01-01

    The peroxisome proliferator-activated receptor alpha (PPARα) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of feno

  7. Overexpression of G0/G1 Switch Gene 2 in Adipose Tissue of Transgenic Quail Inhibits Lipolysis Associated with Egg Laying.

    Science.gov (United States)

    Chen, Paula Renee; Shin, Sangsu; Choi, Young Min; Kim, Elizabeth; Han, Jae Yong; Lee, Kichoon

    2016-03-15

    In avians, yolk synthesis is regulated by incorporation of portomicrons from the diet, transport of lipoproteins from the liver, and release of lipids from adipose tissue; however, the extent to which lipolysis in adipose tissue contributes to yolk synthesis and egg production has yet to be elucidated. G0/G1 switch gene 2 (G0S2) is known to bind and inhibit adipose triglyceride lipase (ATGL), the rate-limiting enzyme in lipolysis. The objective of this study was to determine whether overexpression of the G0S2 gene in adipose tissue could successfully inhibit endogenous ATGL activity associated with egg laying. Two independent lines of transgenic quail overexpressing G0S2 had delayed onset of egg production and reduced number of eggs over a six-week period compared to non-transgenic quail. Although no differences in measured parameters were observed at the pre-laying stage (5 weeks of age), G0S2 transgenic quail had significantly larger interclavicular fat pad weights and adipocyte sizes and lower NEFA concentrations in the serum at early (1 week after laying first egg) and active laying (5 weeks after laying first egg) stages. Overexpression of G0S2 inhibited lipolysis during early and active laying, which drastically shifted the balance towards a net accumulation of triacylglycerols and increased adipose tissue mass. Thereby, egg production was negatively affected as less triacylglycerols were catabolized to produce lipids for the yolk.

  8. MicroRNAs regulate human adipocyte lipolysis: effects of miR-145 are linked to TNF-α.

    Directory of Open Access Journals (Sweden)

    Silvia Lorente-Cebrián

    Full Text Available MicroRNAs (miRNAs are small non-coding RNAs that regulate gene expression and have multiple effects in various tissues including adipose inflammation, a condition characterized by increased local release of the pro-lipolytic cytokine tumor necrosis factor-alpha (TNF-α. Whether miRNAs regulate adipocyte lipolysis is unknown. We set out to determine whether miRNAs affect adipocyte lipolysis in human fat cells. To this end, eleven miRNAs known to be present in human adipose tissue were over-expressed in human in vitro differentiated adipocytes followed by assessments of TNF-α and glycerol levels in conditioned media after 48 h. Three miRNAs (miR-145, -26a and let-7d modulated both parameters in parallel. However, while miR-26a and let-7d decreased, miR-145 increased both glycerol release and TNF-α secretion. Further studies were focused therefore on miR-145 since this was the only stimulator of lipolysis and TNF-α secretion. Time-course analysis demonstrated that miR-145 over-expression up-regulated TNF-α expression/secretion followed by increased glycerol release. Increase in TNF-α production by miR-145 was mediated via activation of p65, a member of the NF-κB complex. In addition, miR-145 down-regulated the expression of the protease ADAM17, resulting in an increased fraction of membrane bound TNF-α, which is the more biologically active form of TNF-α. MiR-145 overexpression also increased the phosphorylation of activating serine residues in hormone sensitive lipase and decreased the mRNA expression of phosphodiesterase 3B, effects which are also observed upon TNF-α treatment in human adipocytes. We conclude that miR-145 regulates adipocyte lipolysis via multiple mechanisms involving increased production and processing of TNF-α in fat cells.

  9. In Vitro lipolysis is associated with whole-body lipid oxidation and weight gain in humans.

    Science.gov (United States)

    Frankl, Joseph; Piaggi, Paolo; Foley, James E; Krakoff, Jonathan; Votruba, Susanne B

    2017-01-01

    To assess the association of adipocyte size with cellular lipolysis and between cellular lipolysis and whole-body lipid oxidation. This study also assessed the association between adipocyte size and cellular lipolysis with weight and fat mass gain. Subjects had assessment of percent body fat (%fat) and adipose tissue biopsy for in vitro lipolysis (n = 325), and a subset of subjects had measurement of whole-body lipid oxidation (n = 112). A subset of subjects (n = 243) returned for repeated measurements of body weight and composition (mean follow-up 8.2 ± 5.5 years). In vitro lipolysis (r = 0.47, P lipolysis (P = 0.04) but not adipocyte size (P = 0.44) was associated with whole-body fat oxidation. Adipocyte size was not associated with rate of percent weight gain (P = 0.20) but was negatively associated with rate of percent fat mass gain (P = 0.01). In vitro lipolysis was negatively associated with rate of percent weight gain (P = 0.02) and had a marginal negative association with rate of percent fat mass gain (P = 0.08). These results indicate inherent characteristics of adipocytes, including size and lipolytic activity, may be important determinants of whole-body lipid oxidation and subsequent weight gain. © 2016 The Obesity Society.

  10. Neural innervation of white adipose tissue and the control of lipolysis.

    Science.gov (United States)

    Bartness, Timothy J; Liu, Yang; Shrestha, Yogendra B; Ryu, Vitaly

    2014-10-01

    White adipose tissue (WAT) is innervated by the sympathetic nervous system (SNS) and its activation is necessary for lipolysis. WAT parasympathetic innervation is not supported. Fully-executed SNS-norepinephrine (NE)-mediated WAT lipolysis is dependent on β-adrenoceptor stimulation ultimately hinging on hormone sensitive lipase and perilipin A phosphorylation. WAT sympathetic drive is appropriately measured electrophysiologically and neurochemically (NE turnover) in non-human animals and this drive is fat pad-specific preventing generalizations among WAT depots and non-WAT organs. Leptin-triggered SNS-mediated lipolysis is weakly supported, whereas insulin or adenosine inhibition of SNS/NE-mediated lipolysis is strongly supported. In addition to lipolysis control, increases or decreases in WAT SNS drive/NE inhibit and stimulate white adipocyte proliferation, respectively. WAT sensory nerves are of spinal-origin and sensitive to local leptin and increases in sympathetic drive, the latter implicating lipolysis. Transsynaptic viral tract tracers revealed WAT central sympathetic and sensory circuits including SNS-sensory feedback loops that may control lipolysis. Copyright © 2014 Elsevier Inc. All rights reserved.

  11. Berberine attenuates cAMP-induced lipolysis via reducing the inhibition of phosphodiesterase in 3T3-L1 adipocytes.

    Science.gov (United States)

    Zhou, Libin; Wang, Xiao; Yang, Ying; Wu, Ling; Li, Fengying; Zhang, Rong; Yuan, Guoyue; Wang, Ning; Chen, Mingdao; Ning, Guang

    2011-04-01

    Berberine, a hypoglycemic agent, has been shown to decrease plasma free fatty acids (FFAs) level in insulin-resistant rats. In the present study, we explored the mechanism responsible for the antilipolytic effect of berberine in 3T3-L1 adipocytes. It was shown that berberine attenuated lipolysis induced by catecholamines, cAMP-raising agents, and a hydrolyzable cAMP analog, but not by tumor necrosis factor α and a nonhydrolyzable cAMP analog. Unlike insulin, the inhibitory effect of berberine on lipolysis in response to isoproterenol was not abrogated by wortmannin, an inhibitor of phosphatidylinositol 3-kinase, but additive to that of PD98059, an extracellular signal-regulated kinase kinase inhibitor. Prior exposure of adipocytes to berberine decreased the intracellular cAMP production induced by isoproterenol, forskolin, and 3-isobutyl-1-methylxanthine (IBMX), along with hormone-sensitive lipase (HSL) Ser-563 and Ser-660 dephosphorylation, but had no effect on perilipin phosphorylation. Berberine stimulated HSL Ser-565 as well as adenosine monophosphate-activated protein kinase (AMPK) phosphorylation. However, compound C, an AMPK inhibitor, did not reverse the regulatory effect of berberine on HSL Ser-563, Ser-660, and Ser-565 phosphorylation, nor the antilipolytic effect of berberine. Knockdown of AMPK using RNA interference also failed to restore berberine-suppressed lipolysis. cAMP-raising agents increased AMPK activity, which was not additive to that of berberine. Stimulation of adipocytes with berberine increased phosphodiesterase (PDE) 3B and PDE4 activity measured by hydrolysis of (3)[H]cAMP. These results suggest that berberine exerts an antilipolytic effect mainly by reducing the inhibition of PDE, leading to a decrease in cAMP and HSL phosphorylation independent of AMPK pathway.

  12. Relationship between site-specific HSL phosphorylation and adipocyte lipolysis in obese women.

    Science.gov (United States)

    Lorente-Cebrián, Silvia; Kulyté, Agné; Hedén, Per; Näslund, Erik; Arner, Peter; Rydén, Mikael

    2011-01-01

    In fat cells of obese humans, basal lipolysis is increased but catecholamine-stimulated lipolysis is blunted. This is linked to decreased expression of hormone-sensitive lipase (HSL). Upon stimulation by cAMP, HSL is phosphorylated at several serine residues (P-Ser(552), P-Ser(649) and P-Ser(650)) leading to enzymatic activation. In contrast, P-Ser(554) prevents phosphorylation at Ser(552) and is thus considered an inactivating site. We hypothesized that differences in HSL phosphorylation could be linked to disturbed adipocyte lipolysis in obesity. Phosphorylation at Ser(552), Ser(554), Ser(650) as well as total HSL and adipose triglyceride lipase (ATGL) protein expression were assessed by Western blot in subcutaneous adipose tissue samples of 32 obese women. Basal and stimulated lipolysis in isolated fat cells were correlated to phosphorylation levels. While there was no correlation between basal lipolysis and P-Ser(650) or P-Ser(554), there was a negative correlation with P-Ser(552) (r = 0.39; p lipolysis. There were no significant correlations between any measure of lipolysis and total levels of HSL and ATGL. In contrast to total HSL and ATGL levels, phosphorylation at Ser(554) and Ser(552), but not at Ser(650), may differentially predict adipocyte lipolysis in vitro. Posttranslational modifications of HSL may therefore constitute an important regulator of adipocyte lipolysis, at least in adipose tissue of obese women. Whether this is also relevant in lean individuals remains to be demonstrated. Copyright © 2011 S. Karger AG, Basel.

  13. Very-low-density lipoprotein (VLDL)-producing and hepatitis C virus-replicating HepG2 cells secrete no more lipoviroparticles than VLDL-deficient Huh7.5 cells.

    Science.gov (United States)

    Jammart, Baptiste; Michelet, Maud; Pécheur, Eve-Isabelle; Parent, Romain; Bartosch, Birke; Zoulim, Fabien; Durantel, David

    2013-05-01

    In the plasma samples of hepatitis C virus (HCV)-infected patients, lipoviroparticles (LVPs), defined as (very-) low-density viral particles immunoprecipitated with anti-β-lipoproteins antibodies are observed. This HCV-lipoprotein association has major implications with respect to our understanding of HCV assembly, secretion, and entry. However, cell culture-grown HCV (HCVcc) virions produced in Huh7 cells, which are deficient for very-low-density lipoprotein (VLDL) secretion, are only associated with and dependent on apolipoprotein E (apoE), not apolipoprotein B (apoB), for assembly and infectivity. In contrast to Huh7, HepG2 cells can be stimulated to produce VLDL by both oleic acid treatment and inhibition of the MEK/extracellular signal-regulated kinase (ERK) pathway but are not permissive for persistent HCV replication. Here, we developed a new HCV cell culture model to study the interaction between HCV and lipoproteins, based on engineered HepG2 cells stably replicating a blasticidin-tagged HCV JFH1 strain (JB). Control Huh7.5-JB as well as HepG2-JB cell lines persistently replicated viral RNA and expressed viral proteins with a subcellular colocalization of double-stranded RNA (dsRNA), core, gpE2, and NS5A compatible with virion assembly. The intracellular RNA replication level was increased in HepG2-JB cells upon dimethyl sulfoxide (DMSO) treatment, MEK/ERK inhibition, and NS5A overexpression to a level similar to that observed in Huh7.5-JB cells. Both cell culture systems produced infectious virions, which were surprisingly biophysically and biochemically similar. They floated at similar densities on gradients, contained mainly apoE but not apoB, and were not neutralized by anti-apoB antibodies. This suggests that there is no correlation between the ability of cells to simultaneously replicate HCV as well as secrete VLDL and their capacity to produce LVPs.

  14. Insulin Regulates Adipocyte Lipolysis via an Akt-Independent Signaling Pathway ▿

    Science.gov (United States)

    Choi, Sarah M.; Tucker, David F.; Gross, Danielle N.; Easton, Rachael M.; DiPilato, Lisa M.; Dean, Abigail S.; Monks, Bob R.; Birnbaum, Morris J.

    2010-01-01

    After a meal, insulin suppresses lipolysis through the activation of its downstream kinase, Akt, resulting in the inhibition of protein kinase A (PKA), the main positive effector of lipolysis. During insulin resistance, this process is ineffective, leading to a characteristic dyslipidemia and the worsening of impaired insulin action and obesity. Here, we describe a noncanonical Akt-independent, phosphoinositide-3 kinase (PI3K)-dependent pathway that regulates adipocyte lipolysis using restricted subcellular signaling. This pathway selectively alters the PKA phosphorylation of its major lipid droplet-associated substrate, perilipin. In contrast, the phosphorylation of another PKA substrate, hormone-sensitive lipase (HSL), remains Akt dependent. Furthermore, insulin regulates total PKA activity in an Akt-dependent manner. These findings indicate that localized changes in insulin action are responsible for the differential phosphorylation of PKA substrates. Thus, we identify a pathway by which insulin regulates lipolysis through the spatially compartmentalized modulation of PKA. PMID:20733001

  15. Insulin regulates adipocyte lipolysis via an Akt-independent signaling pathway.

    Science.gov (United States)

    Choi, Sarah M; Tucker, David F; Gross, Danielle N; Easton, Rachael M; DiPilato, Lisa M; Dean, Abigail S; Monks, Bob R; Birnbaum, Morris J

    2010-11-01

    After a meal, insulin suppresses lipolysis through the activation of its downstream kinase, Akt, resulting in the inhibition of protein kinase A (PKA), the main positive effector of lipolysis. During insulin resistance, this process is ineffective, leading to a characteristic dyslipidemia and the worsening of impaired insulin action and obesity. Here, we describe a noncanonical Akt-independent, phosphoinositide-3 kinase (PI3K)-dependent pathway that regulates adipocyte lipolysis using restricted subcellular signaling. This pathway selectively alters the PKA phosphorylation of its major lipid droplet-associated substrate, perilipin. In contrast, the phosphorylation of another PKA substrate, hormone-sensitive lipase (HSL), remains Akt dependent. Furthermore, insulin regulates total PKA activity in an Akt-dependent manner. These findings indicate that localized changes in insulin action are responsible for the differential phosphorylation of PKA substrates. Thus, we identify a pathway by which insulin regulates lipolysis through the spatially compartmentalized modulation of PKA.

  16. Lipolysis in lipid turnover, cancer cachexia, and obesity-induced insulin resistance.

    Science.gov (United States)

    Arner, Peter; Langin, Dominique

    2014-05-01

    Triglycerides in adipose tissue are rapidly mobilized during times of energy needs via lipolysis, a catabolic process that plays important role in whole body triglyceride turnover. Lipolysis is regulated through cell surface receptors via neurotransmitters, hormones, and paracrine factors that activate various intracellular pathways. These pathways converge on the lipid droplet, the site of action of lipases and cofactors. Fat cell lipolysis is also involved in the pathogenesis of metabolic disorders, and recent human studies have underscored its role in disease states such as cancer cachexia and obesity-induced insulin resistance. We highlight here topics and findings with physiological and clinical relevance, namely lipid turnover in human fat cells and the role of lipolysis in cancer cachexia and obesity-induced insulin resistance. Copyright © 2014 Elsevier Ltd. All rights reserved.

  17. Primary defects in lipolysis and insulin action in skeletal muscle cells from type 2 diabetic individuals

    DEFF Research Database (Denmark)

    Kase, E. T.; Feng, Y. Z.; Badin, P. M.

    2015-01-01

    A decrease in skeletal muscle lipolysis and hormone sensitive-lipase (HSL) expression has been linked to insulin resistance in obesity. The purpose of this study was to identify potential intrinsic defects in lipid turnover and lipolysis in myotubes established from obese and type 2 diabetic...... subjects. Lipid trafficking and lipolysis were measured by pulse-chase assay with radiolabeled substrates in myotubes from non-obese/non-diabetic (lean), obese/non-diabetic (obese) and obese/diabetic (T2D) subjects. Lipolytic protein content and level of Akt phosphorylation were measured by Western blot....... HSL was overexpressed by adenovirus-mediated gene delivery. Myotubes established from obese and T2D subjects had lower lipolysis (-30-40%) when compared to lean, using oleic acid as precursor. Similar observations were also seen for labelled glycerol. Incorporation of oleic acid into diacylglycerol...

  18. Apoptosis inhibitor of macrophage (AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Iwamura, Yoshihiro; Mori, Mayumi; Nakashima, Katsuhiko [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Mikami, Toshiyuki; Murayama, Katsuhisa [Genomic Science Laboratories, Dainippon Sumitomo Pharma Co. Ltd., 3-1-98 Kasugadenaka, Konohana-ku, Osaka 554-0022 (Japan); Arai, Satoko [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan); Miyazaki, Toru, E-mail: tm@m.u-tokyo.ac.jp [Laboratory of Molecular Biomedicine for Pathogenesis, Center for Disease Biology and Integrative Medicine, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-0033 (Japan)

    2012-06-08

    Highlights: Black-Right-Pointing-Pointer AIM induces lipolysis in a distinct manner from that of hormone-dependent lipolysis. Black-Right-Pointing-Pointer AIM ablates activity of peroxisome proliferator-activated receptor in adipocytes. Black-Right-Pointing-Pointer AIM reduces mRNA levels of lipid-droplet coating proteins leading to lipolysis. -- Abstract: Under fasting conditions, triacylglycerol in adipose tissue undergoes lipolysis to supply fatty acids as energy substrates. Such lipolysis is regulated by hormones, which activate lipases via stimulation of specific signalling cascades. We previously showed that macrophage-derived soluble protein, AIM induces obesity-associated lipolysis, triggering chronic inflammation in fat tissue which causes insulin resistance. However, the mechanism of how AIM mediates lipolysis remains unknown. Here we show that AIM induces lipolysis in a manner distinct from that of hormone-dependent lipolysis, without activation or augmentation of lipases. In vivo and in vitro, AIM did not enhance phosphorylation of hormone-sensitive lipase (HSL) in adipocytes, a hallmark of hormone-dependent lipolysis activation. Similarly, adipose tissue from obese AIM-deficient and wild-type mice showed comparable HSL phosphorylation. Consistent with the suppressive effect of AIM on fatty acid synthase activity, the amount of saturated and unsaturated fatty acids was reduced in adipocytes treated with AIM. This response ablated transcriptional activity of peroxisome proliferator-activated receptor (PPAR{gamma}), leading to diminished gene expression of lipid-droplet coating proteins including fat-specific protein 27 (FSP27) and Perilipin, which are indispensable for triacylglycerol storage in adipocytes. Accordingly, the lipolytic effect of AIM was overcome by a PPAR{gamma}-agonist or forced expression of FSP27, while it was synergized by a PPAR{gamma}-antagonist. Overall, distinct modes of lipolysis appear to take place in different physiological

  19. Apoptosis inhibitor of macrophage (AIM) diminishes lipid droplet-coating proteins leading to lipolysis in adipocytes.

    Science.gov (United States)

    Iwamura, Yoshihiro; Mori, Mayumi; Nakashima, Katsuhiko; Mikami, Toshiyuki; Murayama, Katsuhisa; Arai, Satoko; Miyazaki, Toru

    2012-06-08

    Under fasting conditions, triacylglycerol in adipose tissue undergoes lipolysis to supply fatty acids as energy substrates. Such lipolysis is regulated by hormones, which activate lipases via stimulation of specific signalling cascades. We previously showed that macrophage-derived soluble protein, AIM induces obesity-associated lipolysis, triggering chronic inflammation in fat tissue which causes insulin resistance. However, the mechanism of how AIM mediates lipolysis remains unknown. Here we show that AIM induces lipolysis in a manner distinct from that of hormone-dependent lipolysis, without activation or augmentation of lipases. In vivo and in vitro, AIM did not enhance phosphorylation of hormone-sensitive lipase (HSL) in adipocytes, a hallmark of hormone-dependent lipolysis activation. Similarly, adipose tissue from obese AIM-deficient and wild-type mice showed comparable HSL phosphorylation. Consistent with the suppressive effect of AIM on fatty acid synthase activity, the amount of saturated and unsaturated fatty acids was reduced in adipocytes treated with AIM. This response ablated transcriptional activity of peroxisome proliferator-activated receptor (PPARγ), leading to diminished gene expression of lipid-droplet coating proteins including fat-specific protein 27 (FSP27) and Perilipin, which are indispensable for triacylglycerol storage in adipocytes. Accordingly, the lipolytic effect of AIM was overcome by a PPARγ-agonist or forced expression of FSP27, while it was synergized by a PPARγ-antagonist. Overall, distinct modes of lipolysis appear to take place in different physiological situations; one is a supportive response against nutritional deprivation achieved by enhancing lipase activity, and the other is a pathological consequence of obesity, causing subclinical inflammation and metabolic disorders, mediated by abolishing droplet-coating proteins. Copyright © 2012 Elsevier Inc. All rights reserved.

  20. Effect of the presence of protein on lipolysis and lipid oxidation occurring during in vitro digestion of highly unsaturated oils.

    Science.gov (United States)

    Nieva-Echevarría, Bárbara; Goicoechea, Encarnación; Guillén, María D

    2017-11-15

    The effect of the presence of ovalbumin and soy protein isolate on lipolysis and oxidation taking place during in vitro gastrointestinal digestion of slightly oxidized sunflower and flaxseed oils was addressed. The extent of lipolysis, the molar proportions of acyl groups/fatty acids after digestion, and the oxidation products formed were studied by Proton Nuclear Magnetic Resonance. The presence of proteins provoked a higher hydrolysis in triglycerides, a lower decrease of polyunsaturated chains, and a lower generation of oxidation compounds (conjugated dienes in chains having also hydroperoxy/hydroxy groups, epoxides and aldehydes); the formation of hydroxides was clearly favoured over that of hydroperoxides. Study of headspace composition by Solid Phase Microextraction-Gas Chromatography/Mass Spectrometry confirmed that oxidation advanced to a lesser extent in the presence of protein. Thus, amino acids/peptides released during digestion may show antioxidant properties, affecting not only the extent of lipid oxidation, but also reactions pathways. Copyright © 2017 Elsevier Ltd. All rights reserved.

  1. The effect of insulin, TNFα and DHA on the proliferation, differentiation and lipolysis of preadipocytes isolated from large yellow croaker (Pseudosciaena Crocea R..

    Directory of Open Access Journals (Sweden)

    Xinxia Wang

    Full Text Available Fish final product can be affected by excessive lipid accumulation. Therefore, it is important to develop strategies to control obesity in cultivated fish to strengthen the sustainability of the aquaculture industry. As in mammals, the development of adiposity in fish depends on hormonal, cytokine and dietary factors. In this study, we investigated the proliferation and differentiation of preadipocytes isolated from the large yellow croaker and examined the effects of critical factors such as insulin, TNFα and DHA on the proliferation, differentiation and lipolysis of adipocytes. Preadipocytes were isolated by collagenase digestion, after which their proliferation was evaluated. The differentiation process was optimized by assaying glycerol-3-phosphate dehydrogenase (GPDH activity. Oil red O staining and electron microscopy were performed to visualize the accumulated triacylglycerol. Gene transcript levels were measured using SYBR green quantitative real-time PCR. Insulin promoted preadipocytes proliferation, stimulated cell differentiation and decreased lipolysis of mature adipocytes. TNFα and DHA inhibited cell proliferation and differentiation. While TNFα stimulated mature adipocyte lipolysis, DHA showed no lipolytic effect on adipocytes. The expressions of adipose triglyceride lipase (ATGL, fatty acid synthase (FAS, lipoprotein lipase (LPL and peroxisome proliferator-activated receptor α, γ (PPARα, PPARγ were quantified during preadipocytes differentiation and adipocytes lipolysis to partly explain the regulation mechanisms. In summary, the results of this study indicated that although preadipocytes proliferation and the differentiation process in large yellow croaker are similar to these processes in mammals, the effects of critical factors such as insulin, TNFα and DHA on fish adipocytes development are not exactly the same. Our findings fill in the gaps in the basic data regarding the effects of critical factors on adiposity

  2. The effect of insulin, TNFα and DHA on the proliferation, differentiation and lipolysis of preadipocytes isolated from large yellow croaker (Pseudosciaena Crocea R.).

    Science.gov (United States)

    Wang, Xinxia; Huang, Ming; Wang, Yizhen

    2012-01-01

    Fish final product can be affected by excessive lipid accumulation. Therefore, it is important to develop strategies to control obesity in cultivated fish to strengthen the sustainability of the aquaculture industry. As in mammals, the development of adiposity in fish depends on hormonal, cytokine and dietary factors. In this study, we investigated the proliferation and differentiation of preadipocytes isolated from the large yellow croaker and examined the effects of critical factors such as insulin, TNFα and DHA on the proliferation, differentiation and lipolysis of adipocytes. Preadipocytes were isolated by collagenase digestion, after which their proliferation was evaluated. The differentiation process was optimized by assaying glycerol-3-phosphate dehydrogenase (GPDH) activity. Oil red O staining and electron microscopy were performed to visualize the accumulated triacylglycerol. Gene transcript levels were measured using SYBR green quantitative real-time PCR. Insulin promoted preadipocytes proliferation, stimulated cell differentiation and decreased lipolysis of mature adipocytes. TNFα and DHA inhibited cell proliferation and differentiation. While TNFα stimulated mature adipocyte lipolysis, DHA showed no lipolytic effect on adipocytes. The expressions of adipose triglyceride lipase (ATGL), fatty acid synthase (FAS), lipoprotein lipase (LPL) and peroxisome proliferator-activated receptor α, γ (PPARα, PPARγ) were quantified during preadipocytes differentiation and adipocytes lipolysis to partly explain the regulation mechanisms. In summary, the results of this study indicated that although preadipocytes proliferation and the differentiation process in large yellow croaker are similar to these processes in mammals, the effects of critical factors such as insulin, TNFα and DHA on fish adipocytes development are not exactly the same. Our findings fill in the gaps in the basic data regarding the effects of critical factors on adiposity development in fish

  3. Fibroblast Growth Factor 21 Deficiency Attenuates Experimental Colitis-Induced Adipose Tissue Lipolysis

    Directory of Open Access Journals (Sweden)

    Liming Liu

    2017-01-01

    Full Text Available Aims. Nutrient deficiencies are common in patients with inflammatory bowel disease (IBD. Adipose tissue plays a critical role in regulating energy balance. Fibroblast growth factor 21 (FGF21 is an important endocrine metabolic regulator with emerging beneficial roles in lipid homeostasis. We investigated the impact of FGF21 in experimental colitis-induced epididymal white adipose tissue (eWAT lipolysis. Methods. Mice were given 2.5% dextran sulfate sodium (DSS ad libitum for 7 days to induce colitis. The role of FGF21 was investigated using antibody neutralization or knockout (KO mice. Lipolysis index and adipose lipolytic enzymes were determined. In addition, 3T3-L1 cells were pretreated with IL-6, followed by recombinant human FGF21 (rhFGF21 treatment; lipolysis was assessed. Results. DSS markedly decreased eWAT/body weight ratio and increased serum concentrations of free fatty acid (FFA and glycerol, indicating increased adipose tissue lipolysis. eWAT intracellular lipolytic enzyme expression/activation was significantly increased. These alterations were significantly attenuated in FGF21 KO mice and by circulating FGF21 neutralization. Moreover, DSS treatment markedly increased serum IL-6 and FGF21 levels. IL-6 pretreatment was necessary for the stimulatory effect of FGF21 on adipose lipolysis in 3T3-L1 cells. Conclusions. Our results demonstrate that experimental colitis induces eWAT lipolysis via an IL-6/FGF21-mediated signaling pathway.

  4. CD36 level and trafficking are determinants of lipolysis in adipocytes.

    Science.gov (United States)

    Zhou, Dequan; Samovski, Dmitri; Okunade, Adewole L; Stahl, Philip D; Abumrad, Nada A; Su, Xiong

    2012-11-01

    CD36 has been linked to the etiology of insulin resistance and inflammation. We explored its function in regulating adipose tissue lipolysis, which influences fat accumulation by liver and muscle and overall metabolism. Knockdown of CD36 in differentiated 3T3-L1 adipocytes decreased lipolysis in response to 10 μM of the β-adrenergic agonist isoproterenol (by 42%), 10 μM of the adenyl cyclase activator forskolin (by 32%), and 500 μM of the phosphodiesterase (PDE) inhibitor isobutylmethylxanthine (by 33%). All three treatments in the knockdown adipocytes were associated with significant decreases of cAMP levels and of the hormone-sensitive lipase (HSL) and perilipin phosphorylation. An important role for PDE was supported by the lack of inhibition of the lipolysis induced by the poorly hydrolyzable dibutyryl cAMP analog. An additional contributory mechanism was diminished activation of the Src-ERK1/2 pathway. Regulation of lipolysis and lipolytic signaling by CD36 was reproduced with adipose tissue from CD36(-/-) mice. The importance of surface CD36 in this regulation was suggested by the finding that the plasma membrane-impermeable CD36 inhibitor sulfo-N-succinimidyl oleate (20 μM) decreased lipolysis. Interestingly, isoproterenol induced CD36 internalization, and this process was blocked by HSL inhibition, suggesting feedback regulation of adipocyte lipolysis via CD36 trafficking.

  5. Weight loss and lipolysis promote a dynamic immune response in murine adipose tissue

    Science.gov (United States)

    Kosteli, Aliki; Sugaru, Eiji; Haemmerle, Guenter; Martin, Jayne F.; Lei, Jason; Zechner, Rudolf; Ferrante, Anthony W.

    2010-01-01

    Obesity elicits an immune response characterized by myeloid cell recruitment to key metabolic organs, including adipose tissue. However, the response of immune cells to nonpathologic metabolic stimuli has been less well studied, and the factors that regulate the metabolic-dependent accumulation of immune cells are incompletely understood. Here we characterized the response of adipose tissue macrophages (ATMs) to weight loss and fasting in mice and identified a role for lipolysis in ATM recruitment and accumulation. We found that the immune response to weight loss was dynamic; caloric restriction of high-fat diet–fed mice led to an initial increase in ATM recruitment, whereas ATM content decreased following an extended period of weight loss. The peak in ATM number coincided with the peak in the circulating concentrations of FFA and adipose tissue lipolysis, suggesting that lipolysis drives ATM accumulation. Indeed, fasting or pharmacologically induced lipolysis rapidly increased ATM accumulation, adipose tissue chemoattractant activity, and lipid uptake by ATMs. Conversely, dietary and genetic manipulations that reduced lipolysis decreased ATM accumulation. Depletion of macrophages in adipose tissue cultures increased expression of adipose triglyceride lipase and genes regulated by FFA, and increased lipolysis. These data suggest that local lipid fluxes are central regulators of ATM recruitment and that once recruited, ATMs form lipid-laden macrophages that can buffer local increases in lipid concentration. PMID:20877011

  6. Characterization of Eicosanoids Produced by Adipocyte Lipolysis: IMPLICATION OF CYCLOOXYGENASE-2 IN ADIPOSE INFLAMMATION.

    Science.gov (United States)

    Gartung, Allison; Zhao, Jiawei; Chen, Simon; Mottillo, Emilio; VanHecke, Garrett C; Ahn, Young-Hoon; Maddipati, Krishna Rao; Sorokin, Andrey; Granneman, James; Lee, Menq-Jer

    2016-07-29

    Excessive adipocyte lipolysis generates lipid mediators and triggers inflammation in adipose tissue. However, the specific roles of lipolysis-generated mediators in adipose inflammation remain to be elucidated. In the present study, cultured 3T3-L1 adipocytes were treated with isoproterenol to activate lipolysis and the fatty acyl lipidome of released lipids was determined by using LC-MS/MS. We observed that β-adrenergic activation elevated levels of approximately fifty lipid species, including metabolites of cyclooxygenases, lipoxygenases, epoxygenases, and other sources. Moreover, we found that β-adrenergic activation induced cyclooxygenase 2 (COX-2), not COX-1, expression in a manner that depended on activation of hormone-sensitive lipase (HSL) in cultured adipocytes and in the epididymal white adipose tissue (EWAT) of C57BL/6 mice. We found that lipolysis activates the JNK/NFκB signaling pathway and inhibition of the JNK/NFκB axis abrogated the lipolysis-stimulated COX-2 expression. In addition, pharmacological inhibition of COX-2 activity diminished levels of COX-2 metabolites during lipolytic activation. Inhibition of COX-2 abrogated the induction of CCL2/MCP-1 expression by β-adrenergic activation and prevented recruitment of macrophage/monocyte to adipose tissue. Collectively, our data indicate that excessive adipocyte lipolysis activates the JNK/NFκB pathway leading to the up-regulation of COX-2 expression and recruitment of inflammatory macrophages. © 2016 by The American Society for Biochemistry and Molecular Biology, Inc.

  7. A dynamic in vitro lipolysis model. II: Evaluation of the model.

    Science.gov (United States)

    Zangenberg, N H; Müllertz, A; Kristensen, H G; Hovgaard, L

    2001-10-01

    A lipolysis model was characterised and evaluated by investigating the composition of the aqueous phase and the concentration of probucol and danazol in the aqueous phase. Effects of bile salt levels at 5, 10, 20, and 30 mM were investigated. Samples were taken at 0%, 50%, 75% and 95% hydrolysis of the triglycerides, and the aqueous phases were isolated by ultra-centrifugation, whereby the concentrations of bile salts, fatty acids, mono-, di-, triglycerides, and drug substances were measured. At high Ca(2+)-concentrations, bile salts were believed to precipitate with Ca(2+). The concentration of lipolytic products (fatty acids + monoglycerides) was dependent on the bile salt concentration. The ratio between lipolytic product and bile salts was 1.55+/-0.09 (S.D.). This ratio is equivalent to mixed bile salt micelles and vesicles in equilibrium. The aqueous solubility of probucol and danazol was increased in the presence of bile salts. The concentration of danazol in the aqueous phase was dependent on the solubilisation capacity of the aqueous phase. In the case of probucol, the concentration in the aqueous phase was dependent on the partition of probucol between the aqueous phase and the remaining triglyceride phase. This difference between danazol and probucol was attributed to the effect of different lipophilicity.

  8. Very-Low-Density Lipoprotein (VLDL)-Producing and Hepatitis C Virus-Replicating HepG2 Cells Secrete No More Lipoviroparticles than VLDL-Deficient Huh7.5 Cells

    Science.gov (United States)

    Jammart, Baptiste; Michelet, Maud; Pécheur, Eve-Isabelle; Parent, Romain; Bartosch, Birke; Zoulim, Fabien

    2013-01-01

    In the plasma samples of hepatitis C virus (HCV)-infected patients, lipoviroparticles (LVPs), defined as (very-) low-density viral particles immunoprecipitated with anti-β-lipoproteins antibodies are observed. This HCV-lipoprotein association has major implications with respect to our understanding of HCV assembly, secretion, and entry. However, cell culture-grown HCV (HCVcc) virions produced in Huh7 cells, which are deficient for very-low-density lipoprotein (VLDL) secretion, are only associated with and dependent on apolipoprotein E (apoE), not apolipoprotein B (apoB), for assembly and infectivity. In contrast to Huh7, HepG2 cells can be stimulated to produce VLDL by both oleic acid treatment and inhibition of the MEK/extracellular signal-regulated kinase (ERK) pathway but are not permissive for persistent HCV replication. Here, we developed a new HCV cell culture model to study the interaction between HCV and lipoproteins, based on engineered HepG2 cells stably replicating a blasticidin-tagged HCV JFH1 strain (JB). Control Huh7.5-JB as well as HepG2-JB cell lines persistently replicated viral RNA and expressed viral proteins with a subcellular colocalization of double-stranded RNA (dsRNA), core, gpE2, and NS5A compatible with virion assembly. The intracellular RNA replication level was increased in HepG2-JB cells upon dimethyl sulfoxide (DMSO) treatment, MEK/ERK inhibition, and NS5A overexpression to a level similar to that observed in Huh7.5-JB cells. Both cell culture systems produced infectious virions, which were surprisingly biophysically and biochemically similar. They floated at similar densities on gradients, contained mainly apoE but not apoB, and were not neutralized by anti-apoB antibodies. This suggests that there is no correlation between the ability of cells to simultaneously replicate HCV as well as secrete VLDL and their capacity to produce LVPs. PMID:23427158

  9. Expression of the very low-density lipoprotein receptor (VLDL-r), an apolipoprotein-E receptor, in the central nervous system and in Alzheimer`s disease

    Energy Technology Data Exchange (ETDEWEB)

    Christie, R.H.; Chung, Haeyong; Rebeck, G.W.; Hyman, B.T. [Massachusetts General Hospital, Boston, MA (United States)] [and others

    1996-04-01

    The very low density lipoprotein receptor (VLDL-r) is a cell-surface molecule specialized for the internalization of multiple diverse ligands, including apolipoprotein E (apoE)-containing lipoprotein particles, via clathrin-coated pits. Its structure is similar to the low-density lipoprotein receptor (LDL-r), although the two have substantially different systemic distributions and regulatory pathways. The present work examines the distribution of VLDL-r in the central nervous system (CNS) and in relation to senile plaques in Alzheimer disease (AD). VLDL-r is present on resting and activated microglia, particularly those associated with senile plaques (SPs). VLDL-r immunoreactivity is also found in cortical neurons. Two exons of VLDL-r mRNA are differentially spliced in the mature receptor mRNA. One set of splice forms gives rise to receptors containing (or lacking) an extracellular O-linked glycosylation domain near the transmembrane portion of the molecule. The other set of splice forms appears to be brain-specific, and is responsible for the presence or absence of one of the cysteine-rich repeat regions in the binding region of the molecule. Ratios of the receptor variants generated from these splice forms do not differ substantially across different cortical areas or in AD. We hypothesize that VLDL-r might contribute to metabolism of apoE and apoE/A{beta} complexes in the brain. Further characterization of apoE receptors in Alzheimer brain may help lay the groundwork for understanding the role of apoE in the CNS and in the pathophysiology of AD. 43 refs., 5 figs.

  10. Comparison of a reduced carbohydrate and reduced fat diet for LDL, HDL, and VLDL subclasses during 9-months of weight maintenance subsequent to weight loss

    Directory of Open Access Journals (Sweden)

    Vernon Mary C

    2010-06-01

    Full Text Available Abstract Objectives This study compared LDL, HDL, and VLDL subclasses in overweight or obese adults consuming either a reduced carbohydrate (RC or reduced fat (RF weight maintenance diet for 9 months following significant weight loss. Methods Thirty-five (21 RC; 14 RF overweight or obese middle-aged adults completed a 1-year weight management clinic. Participants met weekly for the first six months and bi-weekly thereafter. Meetings included instruction for diet, physical activity, and behavior change related to weight management. Additionally, participants followed a liquid very low-energy diet of ~2092 kJ per day for the first three months of the study. Subsequently, participants followed a dietary plan for nine months that targeted a reduced percentage of carbohydrate (~20% or fat (~30% intake and an energy intake level calculated to maintain weight loss. Lipid subclasses using NMR spectroscopy were analyzed prior to weight loss and at multiple intervals during weight maintenance. Results Body weight change was not significantly different within or between groups during weight maintenance (p > 0.05. The RC group showed significant increases in mean LDL size, large LDL, total HDL, large and small HDL, mean VLDL size, and large VLDL during weight maintenance while the RF group showed increases in total HDL, large and small HDL, total VLDL, and large, medium, and small VLDL (p p > 0.05. Conclusion Some individual lipid subclasses improved in both dietary groups. Large and medium VLDL subclasses increased to a greater extent across weight maintenance in the RF group.

  11. Effects of ultra-high-pressure homogenization treatment on the lipolysis and lipid oxidation of milk during refrigerated storage.

    Science.gov (United States)

    Pereda, Julieta; Ferragut, Victoria; Quevedo, Joan Miquel; Guamis, Buenaventura; Trujillo, Antonio J

    2008-08-27

    Free fatty acid (FFA) release and quantification and lipid oxidation extent of ultra-high-pressure homogenized (UHPH) milk samples were evaluated to assess the effect of UHPH on the susceptibility of milk lipids to lipolysis and oxidation. Milk was UHPH-treated at 200 and 300 MPa with inlet temperatures of 30 and 40 degrees C. UHPH-treated samples were compared to high-pasteurized milk (PA; 90 degrees C, 15 s). Results showed that all FFA increased significantly during storage only in 200 MPa samples. Lipid oxidation was measured as an accumulation of lipid hydroperoxides as the primary oxidation product and malondialdehyde and hexanal as the secondary oxidation products. Samples treated at 300 MPa presented higher malondialdehyde and hexanal content compared to 200 MPa treated-samples and to PA milk.

  12. Primary defects in lipolysis and insulin action in skeletal muscle cells from type 2 diabetic individuals.

    Science.gov (United States)

    Kase, Eili T; Feng, Yuan Z; Badin, Pierre-Marie; Bakke, Siril S; Laurens, Claire; Coue, Marine; Langin, Dominique; Gaster, Michael; Thoresen, G Hege; Rustan, Arild C; Moro, Cedric

    2015-09-01

    A decrease in skeletal muscle lipolysis and hormone sensitive-lipase (HSL) expression has been linked to insulin resistance in obesity. The purpose of this study was to identify potential intrinsic defects in lipid turnover and lipolysis in myotubes established from obese and type 2 diabetic subjects. Lipid trafficking and lipolysis were measured by pulse-chase assay with radiolabeled substrates in myotubes from non-obese/non-diabetic (lean), obese/non-diabetic (obese) and obese/diabetic (T2D) subjects. Lipolytic protein content and level of Akt phosphorylation were measured by Western blot. HSL was overexpressed by adenovirus-mediated gene delivery. Myotubes established from obese and T2D subjects had lower lipolysis (-30-40%) when compared to lean, using oleic acid as precursor. Similar observations were also seen for labelled glycerol. Incorporation of oleic acid into diacylglycerol (DAG) and free fatty acid (FFA) level was lower in T2D myotubes, and acetate incorporation into FFA and complex lipids was also lower in obese and/or T2D subjects. Both protein expression of HSL (but not ATGL) and changes in DAG during lipolysis were markedly lower in cells from obese and T2D when compared to lean subjects. Insulin-stimulated glycogen synthesis (-60%) and Akt phosphorylation (-90%) were lower in myotubes from T2D, however, overexpression of HSL in T2D myotubes did not rescue the diabetic phenotype. In conclusion, intrinsic defects in lipolysis and HSL expression co-exist with reduced insulin action in myotubes from obese T2D subjects. Despite reductions in intramyocellular lipolysis and HSL expression, overexpression of HSL did not rescue defects in insulin action in skeletal myotubes from obese T2D subjects.

  13. Catecholamine-induced lipolysis in adipose tissue and skeletal muscle in obesity.

    Science.gov (United States)

    Jocken, Johan W E; Blaak, Ellen E

    2008-05-23

    Increased fat storage in adipose and non-adipose tissue (e.g. skeletal muscle) characterizes the obese insulin resistant state. Disturbances in pathways of lipolysis may play a role in the development and maintenance of these increased fat stores. A reduced catecholamine-induced lipolysis may contribute to the development and maintenance of increased adipose tissue stores. To data, a reduced hormone-sensitive lipase (HSL) expression is the best characterized defect contributing to this catecholamine resistance. The recently discovered adipose triglyceride lipase (ATGL) seems not to be involved in the catecholamine resistance of lipolysis observed in abdominal subcutaneous adipose tissue of obese subjects, which contrasts with findings in mice studies. So far, little is known on the regulation of skeletal muscle lipolysis. There is evidence of both HSL and ATGL activity and/or expression in skeletal muscle. A blunted fasting and/or catecholamine-induced lipolysis has been reported in skeletal muscle, but data require confirmation. It is tempting to speculate that an imbalance between ATGL and HSL expression results in incomplete lipolysis and increased accumulation of lipid intermediates in skeletal muscle of obese insulin resistant subjects. The latter may inhibit insulin signalling and play a role in the development of type 2 diabetes. This review summarizes the current knowledge on (intracellular) adipose tissue and skeletal muscle lipolysis in obesity, discusses the underlying mechanisms of these disturbances and will finally address the question whether disturbances in the lipolytic pathways may be primary factors in the etiology of obesity or adaptational responses to the obese insulin resistant state.

  14. Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans.

    Science.gov (United States)

    Wang, Yanli; Xie, Cangsang; Diao, Zhiqing; Liang, Bin

    2017-06-26

    Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC). The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid metabolism are largely unknown. Here, we showed that mutations of tax-6 and cnb-1, which respectively encode the catalytic subunit and the regulatory subunit of calcineurin, together with tacrolimus treatment, consistently led to decreased fat accumulation and delayed growth in the nematode Caenorhabditis elegans. In contrast, disruption of the AMP-activated protein kinase (AMPK) encoded by aak-1 and aak-2 reversed the above effects in worms. Moreover, calcineurin deficiency and tacrolimus treatment consistently activated the transcriptional expression of the lipolytic gene atgl-1, encoding triglyceride lipase. Furthermore, RNAi knockdown of atgl-1 recovered the decreased fat accumulation in both calcineurin deficient and tacrolimus treated worms. Collectively, our results reveal that immunosuppressive agent tacrolimus and their target calcineurin may antagonize AMPK to regulate ATGL and lipolysis, thereby providing potential therapy for the application of immunosuppressive agents.

  15. Calcineurin Antagonizes AMPK to Regulate Lipolysis in Caenorhabditis elegans

    Directory of Open Access Journals (Sweden)

    Yanli Wang

    2017-06-01

    Full Text Available Calcineurin is a calcium- and calmodulin-dependent serine/threonine protein phosphatase, and the target of immunosuppressive agent tacrolimus (TAC. The dysfunction of calcineurin, or clinical applications of tacrolimus, have been reported to be associated with dyslipidemia. The underlying mechanisms of calcineurin and tacrolimus in lipid metabolism are largely unknown. Here, we showed that mutations of tax-6 and cnb-1, which respectively encode the catalytic subunit and the regulatory subunit of calcineurin, together with tacrolimus treatment, consistently led to decreased fat accumulation and delayed growth in the nematode Caenorhabditis elegans. In contrast, disruption of the AMP-activated protein kinase (AMPK encoded by aak-1 and aak-2 reversed the above effects in worms. Moreover, calcineurin deficiency and tacrolimus treatment consistently activated the transcriptional expression of the lipolytic gene atgl-1, encoding triglyceride lipase. Furthermore, RNAi knockdown of atgl-1 recovered the decreased fat accumulation in both calcineurin deficient and tacrolimus treated worms. Collectively, our results reveal that immunosuppressive agent tacrolimus and their target calcineurin may antagonize AMPK to regulate ATGL and lipolysis, thereby providing potential therapy for the application of immunosuppressive agents.

  16. Abdominal subcutaneous adipose tissue insulin resistance and lipolysis in patients with non-alcoholic steatohepatitis.

    Science.gov (United States)

    Armstrong, M J; Hazlehurst, J M; Hull, D; Guo, K; Borrows, S; Yu, J; Gough, S C; Newsome, P N; Tomlinson, J W

    2014-07-01

    Systemic insulin resistance (IR) is a primary feature in non-alcoholic steatohepatitis (NASH), however, there remain limited data on tissue-specific insulin sensitivity in vivo. We examined tissue-specific (adipose, muscle and liver) insulin sensitivity and inflammation in 16 European Caucasian patients with biopsy-confirmed NASH and in 15 healthy controls. All underwent a two-step hyperinsulinaemic euglycaemic clamp incorporating stable isotope measurements of carbohydrate and lipid metabolism with concomitant subcutaneous adipose tissue (SAT) microdialysis. Hepatic and muscle insulin sensitivity were decreased in patients with NASH compared with controls, as demonstrated by reduced suppression of hepatic glucose production and glucose disposal (Gd) rates following insulin infusion. In addition, rates of lipolysis were higher in NASH patients with impaired insulin-mediated suppression of free fatty acid levels. At a tissue specific level, abdominal SAT in patients with NASH was severely insulin resistant, requiring >sixfold more insulin to cause ½-maximal suppression of glycerol release when compared with healthy controls. Furthermore, patients with NASH had significantly higher circulating levels of pro-inflammatory adipocytokines than controls. NASH patients have profound IR in the liver, muscle and in particular adipose tissues. This study represents the first in vivo description of dysfunctional SAT in patients with NASH. © 2014 The Authors. Diabetes, Obesity and Metabolism published by JohnWiley & Sons Ltd.

  17. OXIDATIVE STRESS: ITS ROLE IN INSULIN SECRETION, HORMONE RECEPTION BY ADIPOCYTES AND LIPOLYSIS IN ADIPOSE TISSUE

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    V. V. Ivanov

    2014-01-01

    Full Text Available Oxidative stress is one of the pathogenetic components of many diseases during which generation of reactive oxigen species increases and the capacity of the antioxidant protection system diminishes. In the research of the last decades special attention has been given to adipose tissue, production of adipokines by it and their role in development of immunoresistance associated with formation of the metabolic syndrome and diabetes.Search for methods of therapeutic correction of adipokine secretion disorders, their influence on metabolism of separate cells and the organism on the whole as well as development of new approaches to correction of disorders in cell sensitivity to insulin are extremely topical nowadays. Systematization and consolidation of accumulated data allow to determine the strategies of further research more accurately; as a result, we have attempted to summarize and analyze the accumulated data on the role of adipose tissue in oxidative stress development.On the basis of literature data and the results of the personal investigations, the role of adipose tissue in forming oxidative stress in diabetes has been analyzed in the article. Brief description of adipose tissue was given as a secretory organ regulating metabolic processes in adipocytes and influencing functions of various organs and systems of the body. Mechanisms of disorder in insulin secretion as well as development of insulin sesistance in type I diabetes were described along with the contribution of lipolysis in adipose tissue to these processes.

  18. Maraviroc shows differential effects on glucose uptake and lipolysis in human subcutaneous cultured adipocytes in comparison with omental adipocytes

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    P Perez-Matute

    2012-11-01

    Full Text Available Maraviroc (MVC, the first approved CC-chemokine receptor 5 (CCR5 antagonist, is used for treating HIV-1-infected patients with CCR5 tropism. MVC has been proved safe in all respects and showed beneficial effects on lipid profile of HIV patients with dislipidemia. Adipocyte dysfunction seems to be responsible for many metabolic alterations such as insulin resistance and dislipidemia. Subcutaneous and visceral fat depots are not only physiologically but also metabolically different and metabolic disturbances are more closely associated with visceral than subcutaneous fat accumulation. It has been suggested that antiretrovirals affect both fat depots in a different extent. Thus, whether isolated human adipocytes display regio-specific sensitivity to the metabolic effects of MVC have been tested in this study. Human subcutaneous and omental preadipocytes were used as the source of human adipocytes. These cells were treated with therapeutic concentrations of MVC (0.5–25 µM at day 14 post-differentiation (4 and 24 hours of treatment. Glucose utilization, lactate production and glycerol released into the media were measured using an autoanalyzer. Adiponectin secretion was determined by an ELISA array. A dose-dependent increase in glucose uptake was observed in subcutaneous adipocytes treated with MVC (+72% of stimulation for MVC 25 µM, p < 0.01. This stimulatory effect was tissue specific, as no effects were observed in omental adipocytes. MVC did not exert any significant effect on adiponectin secretion. No significant effects were observed on lactate production neither in subcutaneous nor omental adipocytes. Interestingly, 4 hours of treatment with MVC induced a significant increase in the amount of glycerol released into the media by subcutaneous adipocytes (p < 0.001, but this effect disappeared with longer exposure of adipocytes to MVC (24 h. No effects were observed on lipolysis in omental adipocytes although a slight tendency to

  19. Butyrate and other short-chain fatty acids increase the rate of lipolysis in 3T3-L1 adipocytes

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    John M. Rumberger

    2014-10-01

    Full Text Available We determined the effect of butyrate and other short-chain fatty acids (SCFA on rates of lipolysis in 3T3-L1 adipocytes. Prolonged treatment with butyrate (5 mM increased the rate of lipolysis approximately 2–3-fold. Aminobutyric acid and acetate had little or no effect on lipolysis, however propionate stimulated lipolysis, suggesting that butyrate and propionate act through their shared activity as histone deacetylase (HDAC inhibitors. Consistent with this, the HDAC inhibitor trichostatin A (1 µM also stimulated lipolysis to a similar extent as did butyrate. Western blot data suggested that neither mitogen-activated protein kinase (MAPK activation nor perilipin down-regulation are necessary for SCFA-induced lipolysis. Stimulation of lipolysis with butyrate and trichostatin A was glucose-dependent. Changes in AMP-activated protein kinase (AMPK phosphorylation mediated by glucose were independent of changes in rates of lipolysis. The glycolytic inhibitor iodoacetate prevented both butyrate- and tumor necrosis factor-alpha-(TNF-α mediated increases in rates of lipolysis indicating glucose metabolism is required. However, unlike TNF-α– , butyrate-stimulated lipolysis was not associated with increased lactate release or inhibited by activation of pyruvate dehydrogenase (PDH with dichloroacetate. These data demonstrate an important relationship between lipolytic activity and reported HDAC inhibitory activity of butyrate, other short-chain fatty acids and trichostatin A. Given that HDAC inhibitors are presently being evaluated for the treatment of diabetes and other disorders, more work will be essential to determine if these effects on lipolysis are due to inhibition of HDAC.

  20. Serum homocysteine is not independently associated with an atherogenic lipid profile: The Very Large Database of Lipids (VLDL-21) study.

    Science.gov (United States)

    Lupton, Joshua R; Quispe, Renato; Kulkarni, Krishnaji; Martin, Seth S; Jones, Steven R

    2016-06-01

    Hyperhomocysteinemia is an independent risk factor for cardiovascular disease, but the mechanism for this risk remains unclear. While reducing serum total homocysteine (tHcy) has been shown to decrease strokes, there is no evidence for an effect on myocardial infarctions in randomized controlled trials. This study aims to examine the relationship between tHcy and several lipid measures. Our analyses included 18,297 U.S. adults from the Very Large Database of Lipids who had an extended lipid panel including direct measurement of triglycerides (TG), and the cholesterol concentration of low-density lipoprotein (LDL-C), high-density lipoprotein (HDL-C), non-HDL-C, very low-density lipoprotein (VLDL-C), and remnant-lipoprotein cholesterol (RLP-C: IDL-C + VLDL3-C). Additional measurements were tHcy, hemoglobin A1c (HbA1c), insulin, creatinine, and blood urea nitrogen (BUN). Subjects were categorized into tHcy quartiles. Linear regression models were performed using lipids and tHcy as dependent and independent variables respectively, and further adjusted with age, sex, HbA1c, insulin, creatinine, and BUN levels in multivariable regression. In unadjusted analysis, levels of LDL-C (p lipids were eliminated (p-value range: 0.101-0.750) when controlling for age, sex, HbA1c, insulin, creatinine, and BUN. Although high levels of tHcy were associated with 2-6% higher TG-rich lipoproteins in unadjusted analysis, after adjustment for confounders our findings do not support the hypothesis that hyperhomocysteinemia is associated with an atherogenic lipid profile. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  1. Elevated levels of triglycerides and vldl-cholesterol provoke activation of nlrp1 inflammasome in endothelial cells.

    Science.gov (United States)

    Bleda, Silvia; de Haro, Joaquin; Varela, Cesar; Ferruelo, Antonio; Acin, Francisco

    2016-10-01

    Soluble stimuli present in the plasma of patients with peripheral arterial disease (PAD) are capable of directly stimulating intracellular signalling in endothelium. Oxidized-LDL (oxLDL) induces NLRP3 inflammasome activation in macrophages. However, it is not clear how lipid profile affect NLRP1 inflammasome gene expression in endothelial cells. In this study, the effect of cholesterol and TG of plasma of patients with PAD on NLRP1 inflammasome gene expression in human arterial endothelial cells (HAECS) was assessed. We included 113 patients with symptomatic PAD. HAECs were stimulated for 2h using the plasma samples of the study participants. The NLRP1 quantification of the transcription was carried out on the 7500 real-time PCR system using the Taqman® Universal PCR Master Mix and Assays on demand. Relative quantification of the NLRP1 expression was carried out using the ΔΔCt (threshold cycle) comparative method. Plasma from patients with elevated VLDL-cholesterol levels (>33.6mg/dL, the median value of the sample) provoked a higher expression of NLRP1 inflammasome in HAECs (RQ=1.15±0.23 vs. 1.05±0.69; p=0.045), as well as plasma from patients with elevated TGs levels (>168mg/dL, the median value of the sample) (RQ=1.15±0.23 vs. 1.05±0.69; p=0.045). A positive correlation was found between NLRP1 inflammasome expression and VLDL-cholesterol plasma levels (r=0.4; pcholesterol of patients with atherosclerosis, manifested as PAD, promote the in vitro NLRP1 inflammasome expression in HAECs. Copyright © 2016 Elsevier Ireland Ltd. All rights reserved.

  2. The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin.

    Science.gov (United States)

    DiPilato, Lisa M; Ahmad, Faiyaz; Harms, Matthew; Seale, Patrick; Manganiello, Vincent; Birnbaum, Morris J

    2015-08-01

    Inhibition of adipocyte lipolysis by insulin is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance and type 2 diabetes mellitus. The main target of the antilipolytic action of insulin is believed to be phosphodiesterase 3B (PDE3B), whose phosphorylation by Akt leads to accelerated degradation of the prolipolytic second messenger cyclic AMP (cAMP). To test this hypothesis genetically, brown adipocytes lacking PDE3B were examined for their regulation of lipolysis. In Pde3b knockout (KO) adipocytes, insulin was unable to suppress β-adrenergic receptor-stimulated glycerol release. Reexpressing wild-type PDE3B in KO adipocytes fully rescued the action of insulin against lipolysis. Surprisingly, a mutant form of PDE3B that ablates the major Akt phosphorylation site, murine S273, also restored the ability of insulin to suppress lipolysis. Taken together, these data suggest that phosphorylation of PDE3B by Akt is not required for insulin to suppress adipocyte lipolysis. Copyright © 2015, American Society for Microbiology. All Rights Reserved.

  3. ADP-ribosylation factor 6 modulates adrenergic stimulated lipolysis in adipocytes

    Science.gov (United States)

    Liu, Yingqiu; Zhou, Dequan; Abumrad, Nada A.

    2010-01-01

    ADP-ribosylation factor 6 (Arf6) is a small GTPase that influences membrane receptor trafficking and the actin cytoskeleton. In adipocytes, Arf6 regulates the trafficking of the glucose transporter type 4 (GLUT4) and consequently insulin-stimulated glucose transport. Previous studies also indicated a role of Arf6 in adrenergic receptor trafficking, but whether this contributes to the control of lipolysis in adipocytes remains unknown. This was examined in the present study by using RNA interference (RNAi) and pharmaceutical inhibition in murine cultured 3T3-L1 adipocytes. Downregulation of Arf6 by RNAi impairs isoproterenol-stimulated lipolysis specifically but does not alter triacylglycerol (TAG) synthesis or the insulin signaling pathway. Neither total TAG amounts nor TAG fatty acid compositions are altered. The inhibitory effect on lipolysis is mimicked by dynasore, a specific inhibitor for dynamin, which is required for endocytosis. In contrast, lipolysis triggered by reagents that bypass events at the plasma membrane (e.g., forskolin, isobutylmethylxanthine or 8-bromo-cAMP) is not affected. Moreover, Arf6 protein levels in white adipose tissues are markedly increased in ob/ob mice, whereas they are decreased in obesity-resistant CD36 null mice. These changes reflect at least in part alterations in Arf6 mRNA levels. Collectively, these results suggest a role of the endocytic pathway and its regulation by Arf6 in adrenergic stimulation of lipolysis in adipocytes and potentially in the development of obesity. PMID:20107045

  4. The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis.

    Science.gov (United States)

    Lampidonis, Antonis D; Rogdakis, Emmanuel; Voutsinas, Gerassimos E; Stravopodis, Dimitrios J

    2011-05-15

    The ability to store energy in the form of energy-dense triacylglycerol and to mobilize these stores rapidly during periods of low carbohydrate availability or throughout the strong metabolic demand is a highly conserved process, absolutely essential for survival. In the industrialized world the regulation of this pathway is viewed as an important therapeutic target for disease prevention. Adipose tissue lipolysis is a catabolic process leading to the breakdown of triacylglycerols stored in fat cells, and release of fatty acids and glycerol. Mobilization of adipose tissue fat is mediated by the MGL, HSL and ATGL, similarly functioning enzymes. ATGL initiates lipolysis followed by the actions of HSL on diacylglycerol, and MGL on monoacylglycerol. HSL is regulated by reversible phosphorylation on five critical residues. Phosphorylation alone, however, is not enough to activate HSL. Probably, conformational alterations and a translocation from the cytoplasm to lipid droplets are also involved. In accordance, Perilipin functions as a master regulator of lipolysis, protecting or exposing the triacylglycerol core of a lipid droplet to lipases. The prototype processes of hormonal lipolytic control are the β-adrenergic stimulation and suppression by insulin, both of which affect cytoplasmic cyclic AMP levels. Lipolysis in adipocytes is an important process in the management of body energy reserves. Its deregulation may contribute to the symptoms of type 2 diabetes mellitus and other pathological situations. We, herein, discuss the metabolic regulation and function of lipases mediating mammalian lipolysis with a focus on HSL, quoting newly identified members of the lipolytic proteome.

  5. FNDC5 overexpression and irisin ameliorate glucose/lipid metabolic derangements and enhance lipolysis in obesity.

    Science.gov (United States)

    Xiong, Xiao-Qing; Chen, Dan; Sun, Hai-Jian; Ding, Lei; Wang, Jue-Jin; Chen, Qi; Li, Yue-Hua; Zhou, Ye-Bo; Han, Ying; Zhang, Feng; Gao, Xing-Ya; Kang, Yu-Ming; Zhu, Guo-Qing

    2015-09-01

    Irisin is a cleaved and secreted fragment of fibronectin type III domain containing 5 (FNDC5), and contributes to the beneficial effects of exercise on metabolism. Here we report the therapeutical effects of FNDC5/irisin on metabolic derangements and insulin resistance in obesity, and show the lipolysis effect of irisin and its signal molecular mechanism. In obese mice, lentivirus mediated-FNDC5 overexpression enhanced energy expenditure, lipolysis and insulin sensitivity, and reduced hyperlipidemia, hyperglycemia, hyperinsulinism, blood pressure and norepinephrine levels; it increased hormone-sensitive lipase (HSL) expression and phosphorylation, and reduced perilipin level and adipocyte diameter in adipose tissues. Subcutaneous perfusion of irisin reduced hyperlipidemia and hyperglycemia, and improved insulin resistance. Either FNDC5 overexpression or irisin perfusion only induced a tendency toward a slight decrease in body weight in obese mice. In 3T3-L1 adipocytes, irisin enhanced basal lipolysis rather than isoproterenol-induced lipolysis, which were prevented by inhibition of adenylate cyclase or PKA; irisin increased the HSL and perilipin phosphorylation; it increased PKA activity, and cAMP and HSL mRNA levels, but reduced perilipin expression. These results indicate that FNDC5/irisin ameliorates glucose/lipid metabolic derangements and insulin resistance in obese mice, and enhances lipolysis via cAMP-PKA-HSL/perilipin pathway. FNDC5 or irisin can be taken as an effective therapeutic strategy for metabolic disorders. Copyright © 2015 Elsevier B.V. All rights reserved.

  6. Effects of physiological hypercortisolemia on the regulation of lipolysis in subcutaneous adipose tissue.

    Science.gov (United States)

    Samra, J S; Clark, M L; Humphreys, S M; MacDonald, I A; Bannister, P A; Frayn, K N

    1998-02-01

    Cortisol is known to increase whole body lipolysis, yet chronic hypercortisolemia results in increased fat mass. The main aim of the study was to explain these two apparently opposed observations by examining the acute effects of hypercortisolemia on lipolysis in subcutaneous adipose tissue and in the whole body. Six healthy subjects were studied on two occasions. On one occasion hydrocortisone sodium succinate was infused i.v. to induce hypercortisolemia (mean plasma cortisol concentrations, 1500 +/- 100 vs. 335 +/- 25 nmol/L; P adipose tissue of the anterior abdominal wall was studied by measurement of arterio-venous differences, and lipolysis in the whole body was studied by constant infusion of [1,2,3-2H5]glycerol for measurement of the systemic glycerol appearance rate. Hypercortisolemia led to significantly increased arterialized plasma nonesterified fatty acid (NEFA; P adipose tissue, hypercortisolemia decreased veno-arterialized differences for NEFA (P adipose depot. Hypercortisolemia caused a reduction in arterialized plasma TAG concentrations (P adipose tissue lipoprotein lipase). There was no significant difference in plasma insulin concentrations between the control and hypercortisolemia study. Site-specific regulation of the enzymes of intracellular lipolysis (hormone-sensitive lipase) and intravascular lipolysis (lipoprotein lipase) may explain the ability of acute cortisol treatment to increase systemic glycerol and NEFA appearance rates while chronically promoting net central fat deposition.

  7. Lipolysis sensation by white fat afferent nerves triggers brown fat thermogenesis.

    Science.gov (United States)

    Garretson, John T; Szymanski, Laura A; Schwartz, Gary J; Xue, Bingzhong; Ryu, Vitaly; Bartness, Timothy J

    2016-08-01

    Metabolic challenges, such as a cold environment, stimulate sympathetic neural efferent activity to white adipose tissue (WAT) to drive lipolysis, thereby increasing the availability of free fatty acids as one source of fuel for brown adipose tissue (BAT) thermogenesis. WAT is also innervated by sensory nerve fibers that network to metabolic brain areas; moreover, activation of these afferents is reported to increase sympathetic nervous system outflow. However, the endogenous stimuli sufficient to drive WAT afferents during metabolic challenges as well as their functional relation to BAT thermogenesis remain unknown. We tested if local WAT lipolysis directly activates WAT afferent nerves, and then assessed whether this WAT sensory signal affected BAT thermogenesis in Siberian hamsters (Phodopus sungorus). 2-deoxyglucose, a sympathetic nervous system stimulant, caused β-adrenergic receptor dependent increases in inguinal WAT (IWAT) afferent neurophysiological activity. In addition, direct IWAT injections of the β3-AR agonist CL316,243 dose-dependently increased: 1) phosphorylation of IWAT hormone sensitive lipase, an indicator of SNS-stimulated lipolysis, 2) expression of the neuronal activation marker c-Fos in dorsal root ganglion neurons receiving sensory input from IWAT, and 3) IWAT afferent neurophysiological activity, an increase blocked by antilipolytic agent 3,5-dimethylpyrazole. Finally, we demonstrated that IWAT afferent activation by lipolysis triggers interscapular BAT thermogenesis through a neural link between these two tissues. These data suggest IWAT lipolysis activates local IWAT afferents triggering a neural circuit from WAT to BAT that acutely induces BAT thermogenesis.

  8. Nutritional and hormonal control of lipolysis in isolated gilthead seabream (Sparus aurata) adipocytes.

    Science.gov (United States)

    Albalat, A; Gómez-Requeni, P; Rojas, P; Médale, F; Kaushik, S; Vianen, G J; Van den Thillart, G; Gutiérrez, J; Pérez-Sánchez, J; Navarro, I

    2005-07-01

    We examined the effects of diet composition and fasting on lipolysis of freshly isolated adipocytes from gilthead seabream (Sparus aurata). We also analyzed the effects of insulin, glucagon, and growth hormone (GH) in adipocytes isolated from fish fed with different diets. Basal lipolysis, measured as glycerol release, increased proportionally with cell concentration and time of incubation, which validates the suitability of these cell preparations for the study of hormonal regulation of this metabolic process. Gilthead seabream were fed two different diets, FM (100% of fish meal) and PP (100% of plant protein supplied by plant sources) for 6 wk. After this period, each diet group was divided into two groups: fed and fasted (for 11 days). Lipolysis was significantly higher in adipocytes from PP-fed fish than in adipocytes from FM-fed fish. Fasting provoked a significant increase in the lipolytic rate, about threefold in isolated adipocytes regardless of nutritional history. Hormone effects were similar in the different groups: glucagon increased the lipolytic rate, whereas insulin had almost no effect. GH was clearly lipolytic, although the relative increase in glycerol over control was lower in isolated adipocytes from fasted fish compared with fed fish. Together, we demonstrate for the first time that lipolysis, measured in isolated seabream adipocytes, is affected by the nutritional state of the fish. Furthermore, our data suggest that glucagon and especially GH play a major role in the control of adipocyte lipolysis.

  9. Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease.

    Science.gov (United States)

    Nielsen, Thomas Svava; Jessen, Niels; Jørgensen, Jens Otto L; Møller, Niels; Lund, Sten

    2014-06-01

    Lipolysis is the process by which triglycerides (TGs) are hydrolyzed to free fatty acids (FFAs) and glycerol. In adipocytes, this is achieved by sequential action of adipose TG lipase (ATGL), hormone-sensitive lipase (HSL), and monoglyceride lipase. The activity in the lipolytic pathway is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue (AT). This response is crucial in order to provide the organism with a sufficient supply of substrate for oxidative metabolism. However, failure to efficiently suppress lipolysis when FFA demands are low can have serious metabolic consequences and is believed to be a key mechanism in the development of type 2 diabetes in obesity. As the discovery of ATGL in 2004, substantial progress has been made in the delineation of the remarkable complexity of the regulatory network controlling adipocyte lipolysis. Notably, regulatory mechanisms have been identified on multiple levels of the lipolytic pathway, including gene transcription and translation, post-translational modifications, intracellular localization, protein-protein interactions, and protein stability/degradation. Here, we provide an overview of the recent advances in the field of AT lipolysis with particular focus on the molecular regulation of the two main lipases, ATGL and HSL, and the intracellular and extracellular signals affecting their activity.

  10. Changes on physico-chemical, textural, lipolysis and volatile compounds during the manufacture of dry-cured foal "cecina".

    Science.gov (United States)

    Lorenzo, José M

    2014-01-01

    The changes in the physico-chemical and textural properties, lipolysis and volatile compounds during the manufacture of dry-cured foal "cecina" were studied. The pH increased during the last stages of processing but gradually declined over the curing period. TBARS values, hardness and chewiness increased with processing time from 0.14, 2.74 and 0.83 to 3.49 mg malonaldehyde/kg, 20.33 kg and 5.05 kg∗mm, respectively. Ripening time also affected the colour parameters: lightness (L*), redness (a*) and yellowness (b*) (Pcecina", including esters, aldehydes, aliphatic hydrocarbons, branched hydrocarbons, alcohols, aromatic hydrocarbons, furans, ketones. Aldehydes reached their maximum level at the end of the post-salting stage. In the final product, esters became the dominant chemical compounds.

  11. Tumor necrosis factor-alpha directly stimulates the overproduction of hepatic apolipoprotein B100-containing VLDL via impairment of hepatic insulin signaling.

    Science.gov (United States)

    Insulin resistant states are commonly associated with both increased circulating levels of tumor necrosis factor (TNF-a) and hepatic overproduction of very low density lipoproteins (VLDL). In the present study, we examined the potential mechanistic link between TNF-a and hepatic overproduction of ap...

  12. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    NARCIS (Netherlands)

    Schweiger, M.; Paar, M.; Eder, C.; Brandis, J.; Moser, E.; Gorkiewisz, G.; Grond, S.; Radner, F.P.W.; Cerk, I.; Cornaciu, I.; Oberer, M.; Kersten, A.H.; Zechner, R.; Zimmermann, M.B.; Lass, A.

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL)5, which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 sw

  13. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    NARCIS (Netherlands)

    Schweiger, M.; Paar, M.; Eder, C.; Brandis, J.; Moser, E.; Gorkiewisz, G.; Grond, S.; Radner, F.P.W.; Cerk, I.; Cornaciu, I.; Oberer, M.; Kersten, A.H.; Zechner, R.; Zimmermann, M.B.; Lass, A.

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL)5, which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 sw

  14. In vitro digestion kinetics of excipients for lipid-based drug delivery and introduction of a relative lipolysis half life.

    Science.gov (United States)

    Arnold, Yvonne E; Imanidis, Georgios; Kuentz, Martin

    2012-10-01

    Lipid-based drug delivery systems are widely used for enhancing the solubility of poorly water soluble drugs in the gastro-intestinal tract. Following oral intake, lipid systems undergo digestion in the stomach as well as the intestine. Lipolysis is here a complex process at the oil/water interface, influenced by numerous factors. To study the digestibility of nine excipients often used in lipid-based drug delivery systems. In addition, we introduced a mathematical model to describe in vitro lipolysis kinetics. A relative lipolysis half life was defined using the reference excipient medium-chain triglycerides. Using pH-stat equipment, the NaOH consumption was determined in an in vitro lipolysis assay. We identified two classes of excipients. Some additives were partially hydrolysed, whereas other excipients displayed complete lipolysis. For the latter class, a simplified mathematical model provided a good first approximation of initial lipolysis kinetics. Digestion characterization of excipients is important for the development of lipid-based delivery systems. The applied kinetic model and the concept of a relative lipolysis half life seemed to be promising tools for comparing in vitro lipolysis results.

  15. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase

    NARCIS (Netherlands)

    Schweiger, M.; Paar, M.; Eder, C.; Brandis, J.; Moser, E.; Gorkiewisz, G.; Grond, S.; Radner, F.P.W.; Cerk, I.; Cornaciu, I.; Oberer, M.; Kersten, A.H.; Zechner, R.; Zimmermann, M.B.; Lass, A.

    2012-01-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL)5, which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1

  16. Characterising lipid lipolysis and its implication in lipid-based formulation development

    DEFF Research Database (Denmark)

    Thomas, Nicky; Holm, Rene; Rades, Thomas

    2012-01-01

    . Unlike conventional formulations, LBDDS are susceptible to digestion in the gastrointestinal tract, the interplay of delivery system, drug and physiology ultimately effecting drug disposition. In vitro lipolysis has become an important technique to mimic the enzymatic degradation. For the better......Facing the increasing number of poorly water-soluble drugs, pharmaceutical scientists are required to break new grounds for the delivery of these pharmaceutically problematic drugs. Lipid-based drug delivery systems (LBDDS) have received increased interest as a novel drug delivery platform during...... understanding of how LBDDS promote drug delivery, in vitro lipolysis requires advanced characterisation methods. In this review, the physiological background of lipid digestion is followed by a thorough summary of the techniques that are currently used to characterise in vitro lipolysis. It would be desirable...

  17. Starter bacteria are the prime agents of lipolysis in cheddar cheese.

    Science.gov (United States)

    Hickey, Dara K; Kilcawley, Kieran N; Beresford, Tom P; Wilkinson, Martin G

    2006-10-18

    To assess the contribution of starter lactic acid bacteria (LAB) to lipolysis in Cheddar cheese, the evolution of free fatty acids (FFAs) was monitored in Cheddar cheeses manufactured from pasteurized milks with or without starter. Starter-free cheeses were acidified by a combination of lactic acid and glucono-delta-lactone. Starter cultures were found to actively produce FFAs in the cheese vat, and mean levels of FFAs were significantly higher in starter cheeses over ripening. The contribution of nonstarter LAB toward lipolysis appears minimal, especially in starter-acidified cheeses. It is postulated that the moderate increases in FFAs in Cheddar cheese are primarily due to lack of access of esterase of LAB to suitable lipid substrate. The results of this study indicate that starter esterases are the primary contributors to lipolysis in Cheddar cheese made from good quality pasteurized milk.

  18. Fat in flames: influence of cytokines and pattern recognition receptors on adipocyte lipolysis.

    Science.gov (United States)

    Grant, Ryan W; Stephens, Jacqueline M

    2015-08-01

    Adipose tissue has the largest capacity to store energy in the body and provides energy through the release of free fatty acids during times of energy need. Different types of immune cells are recruited to adipose tissue under various physiological conditions, indicating that these cells contribute to the regulation of adipose tissue. One major pathway influenced by a number of immune cells is the release of free fatty acids through lipolysis during both physiological (e.g., cold stress) and pathophysiological processes (e.g., obesity, type 2 diabetes). Adipose tissue expansion during obesity leads to immune cell infiltration and adipose tissue remodeling, a homeostatic process that promotes inflammation in adipose tissue. The release of proinflammatory cytokines stimulates lipolysis and causes insulin resistance, leading to adipose tissue dysfunction and systemic disruptions of metabolism. This review focuses on the interactions of cytokines and other inflammatory molecules that regulate adipose tissue lipolysis during physiological and pathophysiological states. Copyright © 2015 the American Physiological Society.

  19. The influence of sexual hormones on lipogenesis and lipolysis in rat fat cells

    DEFF Research Database (Denmark)

    Hansen, Finn Mølgård; Fahmy, N; Nielsen, Jens Høiriis

    1980-01-01

    synthesis and the lipolysis oscillated considerably more in fat cells from female rats than in fat cells from male rats. This was found to be due to the oestrous cycle, since the fatty acid synthesis was high in prooestrus and low in both oestrus and dioestrus, while the lipolysis was higher in oestrus....... Since these rats were fasted three hours before the experiments, the results were not due to differences in food intake. It is concluded that fat cell metabolism is influenced by sexual hormones. The results are compatible with the hypothesis that the variation in food intake due to sexual hormones......The insulin-stimulated conversion of glucose to fatty acids (fatty acid synthesis) and the maximally norepinephrine-stimulated lipolysis were studied in isolated fat cells from normal male and female rats, ovariectomized rats and sexual hormone-treated normal and ovariectomized rats. The fatty acid...

  20. Pleiotropic regulation of mitochondrial function by adipose triglyceride lipase-mediated lipolysis.

    Science.gov (United States)

    Kratky, Dagmar; Obrowsky, Sascha; Kolb, Dagmar; Radovic, Branislav

    2014-01-01

    Lipolysis is defined as the catabolism of triacylglycerols (TGs) stored in cellular lipid droplets. Recent discoveries of essential lipolytic enzymes and characterization of numerous regulatory proteins and mechanisms have fundamentally changed our perception of lipolysis and its impact on cellular metabolism. Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme for TG catabolism in most cells and tissues. This review focuses on recent advances in understanding the (patho)physiological impact due to defective lipolysis by ATGL deficiency on mitochondrial (dys)function. Depending on the type of cells and tissues investigated, absence of ATGL has pleiotropic roles in mitochondrial function. Copyright © 2013 The Authors. Published by Elsevier Masson SAS.. All rights reserved.

  1. Dissecting adipose tissue lipolysis: molecular regulation and implications for metabolic disease

    DEFF Research Database (Denmark)

    Nielsen, Thomas Svava; Jessen, Niels; Jørgensen, Jens Otto L;

    2014-01-01

    is tightly regulated by hormonal and nutritional factors. Under conditions of negative energy balance such as fasting and exercise, stimulation of lipolysis results in a profound increase in FFA release from adipose tissue. This response is crucial in order to provide the organism with a sufficient supply......Lipolysis is the process by which triglycerides are hydrolyzed to free fatty acids (FFA) and glycerol. In adipocytes, this is achieved by the sequential action of Adipose Triglyceride Lipase (ATGL), Hormone Sensitive Lipase (HSL) and Monoglyceride Lipase (MGL). The activity in the lipolytic pathway...... localization, protein-protein interactions, and protein stability/degradation. Here, we provide an overview of the recent advances in the field of adipose tissue lipolysis with particular focus on the molecular regulation of the two main lipases, ATGL and HSL and the intracellular and extracellular signals...

  2. The expression of type III hyperlipoproteinemia: involvement of lipolysis genes

    Science.gov (United States)

    Henneman, Peter; van der Sman-de Beer, Femke; Moghaddam, Payman Hanifi; Huijts, Petra; Stalenhoef, Anton FH; Kastelein, John JP; van Duijn, Cornelia M; Havekes, Louis M; Frants, Rune R; van Dijk, Ko Willems; Smelt, Augustinus HM

    2009-01-01

    Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In addition, 188 normolipidemic Dutch control panels (NDCP) and 141 hypertriglyceridemic (HTG) patients were genotyped as well. No associations were found for four HL gene polymorphisms and two LPL gene polymorphisms and type III HLP. The frequency of the rare allele of APOC3 3238 G>C and APOA5 −1131 T>C (in linkage disequilibrium) was significantly higher in type III HLP patients when compared with normolipidemic E2/2 subjects, 15.6 vs 6.9% and 15.1 vs 5.8%, respectively, (PC polymorphism and LPL c.27 G>A mutation were higher in type III HLP patients, though not significant. Some 58% of the type III HLP patients carried either the APOA5 −1131 T>C, c.56 G>C and/or LPL c.27 G>A mutation as compared to 27% of the normolipidemic APOE2/2 subjects (odds ratio 3.7, 95% confidence interval=1.8–7.5, PC/APOA5 −1131 T>C polymorphism showed a more severe hyperlipidemia than patients without this polymorphism. Polymorphisms in lipolysis genes associate with the expression and severity of type III HLP in APOE2/2. PMID:19034316

  3. A history of previous gestational diabetes mellitus is associated with adverse changes in insulin secretion and VLDL metabolism independently of increased intrahepatocellular lipid.

    Science.gov (United States)

    Forbes, S; Godsland, I F; Taylor-Robinson, S D; Bell, J D; Thomas, E L; Patel, N; Hamilton, G; Parker, K H; Marshall, I; Gray, C D; Bedford, D; Caslake, M; Walker, B R; Johnston, D G

    2013-09-01

    We have previously reported a high prevalence of non-alcoholic fatty liver disease (NAFLD) among women with previous gestational diabetes mellitus (pGDM). We wanted to confirm that intrahepatocellular lipid (IHCL) is associated with pGDM independently of adiposity and determine: (1) if VLDL metabolism is dysregulated; and (2) the extent to which NAFLD and IHCL account for the dysmetabolic phenotype in pGDM. We analysed data from a cohort of 234 women (114 with pGDM) and identified effects of pGDM on lipid and glucoregulation that were independent of ultrasound-diagnosed NAFLD. We then measured IHCL by MR spectroscopy in a representative subgroup (n = 36) and conducted detailed metabolic studies (IVGTT, VLDL apolipoprotein B [apoB] kinetics and palmitate turnover) and measurement of regional body fat by MRI to demonstrate effects of IHCL that were independent of a history of pGDM. pGDM was associated with increased IHCL (p = 0.04) after adjustment for adiposity. Independently of IHCL, pGDM was associated with a lower IVGTT disposition index (p = 0.02) and acute insulin response to glucose (pGDM+/NAFLD-, 50% lower; pGDM+/NAFLD+, 36% lower; effect of pGDM, p = 0.03), increased VLDL apoB pool size (pGDM+/NAFLD-, 3.1-fold higher; pGDM+/NAFLD+, 1.2-fold higher; effect of pGDM, p = 0.02) and, at borderline significance (p = 0.05), increased rate of VLDL apoB synthesis. pGDM is associated with increased IHCL independently of adiposity. The increased liver fat contributes to the phenotype, but pGDM status is independently associated with diminished insulin secretion and (shown for the first time) augmented VLDL metabolism. IHCL with pGDM may compound a dysmetabolic phenotype.

  4. Inhibition of Lipolysis Ameliorates Diabetic Phenotype in a Mouse Model of Obstructive Sleep Apnea.

    Science.gov (United States)

    Weiszenstein, Martin; Shimoda, Larissa A; Koc, Michal; Seda, Ondrej; Polak, Jan

    2016-08-01

    Obstructive sleep apnea (OSA) is associated with insulin resistance, glucose intolerance, and type 2 diabetes. Causal mechanisms mediating this association are not well defined; however, augmented lipolysis in adipose might be involved. Here, we investigated the effect of acipimox treatment (lipolysis inhibitor) on glucose tolerance and insulin sensitivity in mice exposed to intermittent hypoxia (IH). C57BL6/J mice were exposed for 14 days to IH or control conditions. IH was created by decreasing the fraction of inspired oxygen from 20.9 to 6.5%, 60 times/h. Control exposure was air (fraction of inspired oxygen, 20.9%) delivered at an identical flow rate. Acipimox was provided in drinking water (0.5 g/ml) during exposures. After exposures, intraperitoneal insulin (0.5 IU/kg) and glucose (1 g/kg) tolerance tests were performed, and primary adipocytes were isolated for lipolysis experiments. IH elevated fasting glucose by 51% and worsened glucose tolerance and insulin sensitivity by 33 and 102%, respectively. In parallel, IH increased spontaneous lipolysis by 264%, and reduced epididymal fat mass by 15% and adipocyte size by 8%. Acipimox treatment prevented IH-induced lipolysis and increased epididymal fat mass and adipocyte size by 19 and 10%, respectively. Acipimox fully prevented IH-induced impairments in fasting glycemia, glucose tolerance, and insulin sensitivity. For all reported results, P less than 0.05 was considered significant. Augmented lipolysis contributes to insulin resistance and glucose intolerance observed in mice exposed to IH. Acipimox treatment ameliorated the metabolic consequences of IH and might represent a novel treatment option for patients with obstructive sleep apnea.

  5. In vivo effects of interferon-alpha and interferon-gamma on lipolysis and ketogenesis.

    Science.gov (United States)

    Memon, R A; Feingold, K R; Moser, A H; Doerrler, W; Grunfeld, C

    1992-10-01

    The host response to infection and cancer produces disturbances in fatty acid (FA) oxidation and ketogenesis. Interferons (IFNs) stimulate lipolysis in cultured adipocytes. Since FA mobilization is a major stimulus for ketogenesis, we studied the effect of IFN alpha and IFN gamma on lipolysis and ketogenesis in intact mice. Both IFNs acutely stimulated lipolysis; however, their effects on ketogenesis differed. INF gamma increased serum and hepatic ketone body levels in parallel to its effect on serum FFA, whereas IFN alpha exerted a biphasic effect on ketogenesis. At low doses, IFN alpha increased serum and hepatic ketone body levels, whereas at higher doses, this ketogenic effect was abolished. To determine the mechanism of the biphasic response, we studied the effect of IFN alpha on hepatic malonyl-coenzyme-A (malonyl-CoA), the first committed intermediate in FA synthesis and an inhibitor of FA oxidation and ketogenesis. At low doses, IFN alpha had no effect on malonyl-CoA; however, higher doses of IFN alpha significantly increased malonyl-CoA levels, which could counterbalance its mobilization of FFA. In contrast, INF gamma had little effect on malonyl-CoA, and hence, the FA oxidation was not opposed. By using phenylisopropyladenosine to block IFN-induced lipolysis, we found that in the absence of increased FA flux, INF gamma did not exert a ketogenic effect. However, when IFN alpha-induced lipolysis was blocked, the higher doses of IFN alpha that raise malonyl-CoA levels were antiketogenic. These data suggest that both IFNs exert a ketogenic effect by stimulating lipolysis, but at higher doses the ketogenic effect of IFN alpha is counteracted by its effect on hepatic FA synthesis.

  6. Relations between basic milk components and free fatty acid content in Holstein cow milk as lipolysis parameter

    Directory of Open Access Journals (Sweden)

    Luděk Stádník

    2015-02-01

    Full Text Available The aim of this study was to evaluate in detail the relationship between the basic milk components (fat and protein percentage and the free fatty acids (FFA content, as indicators of spontaneous and/or induced lipolysis. The additional aim of the study was to compare the FFA content of milk with respect to spontaneous and induced lipolysis. Milking was carried out in herringbone parlour twice a day. In total, 540 milk samples were obtained for evaluation of spontaneous (n=240 and induced lipolysis (n=300. The milk samples for determination of basic milk components and FFA (li¬polysis levels were collected during four subsequent lactation weeks. Milk samples for spontaneous lipolysis detection were taken directly in parlour immediately after milking using the ICAR methodology and subsequently grouped. Induced lipolysis was observed from bulk milk in time 0, 1, 2, 3, and 4 hours after milking (T0-T4. The evaluation of basic components and FFA content was carried on MILKOSCAN F120 (Foss Electronic; Denmark. Statistical evaluation was carried out using SAS 9.3. (SAS/STAT® 9.3, 2011. An increase of one percentage of milk fat was equal to 0.318 mmol x 100 g-1 FFA decline (spontaneous lipolysis or from 0.232 to 0.370 mmol x 100 g-1 FFA decline (induced lipolysis T0-T4 respectively. One percentage increase of milk protein was equal to 1.219 mmol x 100 g-1 FFA increase (spontaneous lipolysis or 0.421 to 1.531 mmol x 100 g-1 FFA decrease (induced lipolysis T0 - T4 respectively. Significant differences (P<0.01 were detected among FFA content in relation to spontaneous and induced lipolysis evaluated during storage and cooling after milking. The minimal differences were detected between the FFA content during 4 hours cooling and storage of milk in the tank.

  7. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation

    DEFF Research Database (Denmark)

    Rittig, Nikolaj; Bach, Ermina; Thomsen, Henrik Holm;

    2016-01-01

    = 0.001) compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL) at ser650 in adipose tissue (p = 0.03), a trend towards elevated pHSL at ser552 (p = 0.09) and cAMP-dependent protein kinase A (PKA) phosphorylation of perilipin 1 (PLIN1) (p...... lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces behind the increased lipolysis observed in the early stages of acute...

  8. A beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion in mice.

    Science.gov (United States)

    Attané, Camille; Peyot, Marie-Line; Lussier, Roxane; Poursharifi, Pegah; Zhao, Shangang; Zhang, Dongwei; Morin, Johane; Pineda, Marco; Wang, Shupei; Dumortier, Olivier; Ruderman, Neil B; Mitchell, Grant A; Simons, Brigitte; Madiraju, S R Murthy; Joly, Erik; Prentki, Marc

    2016-12-01

    To directly assess the role of beta cell lipolysis in insulin secretion and whole-body energy homeostasis, inducible beta cell-specific adipose triglyceride lipase (ATGL)-deficient (B-Atgl-KO) mice were studied under normal diet (ND) and high-fat diet (HFD) conditions. Atgl (flox/flox) mice were cross-bred with Mip-Cre-ERT mice to generate Mip-Cre-ERT(/+);Atgl (flox/flox) mice. At 8 weeks of age, these mice were injected with tamoxifen to induce deletion of beta cell-specific Atgl (also known as Pnpla2), and the mice were fed an ND or HFD. ND-fed male B-Atgl-KO mice showed decreased insulinaemia and glucose-induced insulin secretion (GSIS) in vivo. Changes in GSIS correlated with the islet content of long-chain saturated monoacylglycerol (MAG) species that have been proposed to be metabolic coupling factors for insulin secretion. Exogenous MAGs restored GSIS in B-Atgl-KO islets. B-Atgl-KO male mice fed an HFD showed reduced insulinaemia, glycaemia in the fasted and fed states and after glucose challenge, as well as enhanced insulin sensitivity. Moreover, decreased insulinaemia in B-Atgl-KO mice was associated with increased energy expenditure, and lipid metabolism in brown (BAT) and white (WAT) adipose tissues, leading to reduced fat mass and body weight. ATGL in beta cells regulates insulin secretion via the production of signalling MAGs. Decreased insulinaemia due to lowered GSIS protects B-Atgl-KO mice from diet-induced obesity, improves insulin sensitivity, increases lipid mobilisation from WAT and causes BAT activation. The results support the concept that fuel excess can drive obesity and diabetes via hyperinsulinaemia, and that an islet beta cell ATGL-lipolysis/adipose tissue axis controls energy homeostasis and body weight via insulin secretion.

  9. Report of the First Workshop on Very Large Digital Libraries - VLDL2008

    OpenAIRE

    Manghi, Paolo; Pagano, Pasquale; Zezula, Pavel

    2008-01-01

    In today's information society the demand for Digital Li-braries is changing. The implementation of nowadays Dig-ital Libraries is more demanding than in the past. Information consumers are facing with the need to have access and elaborate over an ever growing and heterogeneous information space while information providers are interested in satisfying such needs by providing rich and organised views over such information deluge. Because of their fundamental role of information production and ...

  10. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet

    NARCIS (Netherlands)

    Diepen, J.A. van; Vroegrijk, I.O.C.M.; Berbée, J.F.P.; Shoelson, S.E.; Romijn, J.A.; Havekes, L.M.; Rensen, P.C.N.; Voshol, P.J.

    2011-01-01

    Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-?B activity but also reduces hypertriglyceridemia in humans. The aim of this

  11. Aspirin reduces hypertriglyceridemia by lowering VLDL-triglyceride production in mice fed a high-fat diet.

    NARCIS (Netherlands)

    Diepen, J.A. van; Vroegrijk, I.O.; Berbee, J.F.; Shoelson, S.E.; Romijn, J.A.; Havekes, L.M.; Rensen, P.C.; Voshol, P.J.

    2011-01-01

    Systemic inflammation is strongly involved in the pathophysiology of the metabolic syndrome, a cluster of metabolic risk factors that includes hypertriglyceridemia. Aspirin treatment lowers inflammation via inhibition of NF-kappaB activity but also reduces hypertriglyceridemia in humans. The aim of

  12. Rosuvastatin reduces plasma lipids by inhibiting VLDL production and enhancing hepatobiliary lipid excretion in ApoE*3-Leiden mice

    NARCIS (Netherlands)

    Delsing, DJM; Post, SM; Groenendijk, M; Solaas, K; van der Boom, H; van Duyvenvoorde, W; de Wit, ECM; Bloks, VW; Kuipers, F; Havekes, LM; Princen, HMG

    The present study was designed to investigate the lipid-lowering properties and mechanisms of action of a new HMG-CoA reductase inhibitor, rosuvastatin, in female ApoE*3-Leiden transgenic mice. Mice received a high fat/cholesterol (HFC) diet containing either rosuvastatin (0 [control], 0.00125%,

  13. Endogenous apoC-I increases hyperlipidemia in apoE-knockout mice by stimulating VLDL production and inhibiting LPL

    NARCIS (Netherlands)

    Westerterp, M.; Haan, W. de; Berbée, J.F.P.; Havekes, L.M.; Rensen, P.C.N.

    2006-01-01

    Previous studies have shown that overexpression of human apolipoprotein C-I (apoC-I) results in moderate hypercholesterolemia and severe hypertriglyceridemia in mice in the presence and absence of apoE. We assessed whether physiological endogenous apoC-I levels are sufficient to modulate plasma

  14. MicroRNA profiling links miR-378 to enhanced adipocyte lipolysis in human cancer cachexia.

    Science.gov (United States)

    Kulyté, Agné; Lorente-Cebrián, Silvia; Gao, Hui; Mejhert, Niklas; Agustsson, Thorhallur; Arner, Peter; Rydén, Mikael; Dahlman, Ingrid

    2014-02-01

    Cancer cachexia is associated with pronounced adipose tissue loss due to, at least in part, increased fat cell lipolysis. MicroRNAs (miRNAs) have recently been implicated in controlling several aspects of adipocyte function. To gain insight into the possible impact of miRNAs on adipose lipolysis in cancer cachexia, global miRNA expression was explored in abdominal subcutaneous adipose tissue from gastrointestinal cancer patients with (n = 10) or without (n = 11) cachexia. Effects of miRNA overexpression or inhibition on lipolysis were determined in human in vitro differentiated adipocytes. Out of 116 miRNAs present in adipose tissue, five displayed distinct cachexia-associated expression according to both microarray and RT-qPCR. Four (miR-483-5p/-23a/-744/-99b) were downregulated, whereas one (miR-378) was significantly upregulated in cachexia. Adipose expression of miR-378 associated strongly and positively with catecholamine-stimulated lipolysis in adipocytes. This correlation is most probably causal because overexpression of miR-378 in human adipocytes increased catecholamine-stimulated lipolysis. In addition, inhibition of miR-378 expression attenuated stimulated lipolysis and reduced the expression of LIPE, PLIN1, and PNPLA2, a set of genes encoding key lipolytic regulators. Taken together, increased miR-378 expression could play an etiological role in cancer cachexia-associated adipose tissue loss via effects on adipocyte lipolysis.

  15. G0/G1 switch gene-2 regulates human adipocyte lipolysis by affecting activity and localization of adipose triglyceride lipase.

    Science.gov (United States)

    Schweiger, Martina; Paar, Margret; Eder, Christina; Brandis, Janina; Moser, Elena; Gorkiewicz, Gregor; Grond, Susanne; Radner, Franz P W; Cerk, Ines; Cornaciu, Irina; Oberer, Monika; Kersten, Sander; Zechner, Rudolf; Zimmermann, Robert; Lass, Achim

    2012-11-01

    The hydrolysis of triglycerides in adipocytes, termed lipolysis, provides free fatty acids as energy fuel. Murine lipolysis largely depends on the activity of adipose triglyceride lipase (ATGL), which is regulated by two proteins annotated as comparative gene identification-58 (CGI-58) and G0/G1 switch gene-2 (G0S2). CGI-58 activates and G0S2 inhibits ATGL activity. In contrast to mice, the functional role of G0S2 in human adipocyte lipolysis is poorly characterized. Here we show that overexpression or silencing of G0S2 in human SGBS adipocytes decreases and increases lipolysis, respectively. Human G0S2 is upregulated during adipocyte differentiation and inhibits ATGL activity in a dose-dependent manner. Interestingly, C-terminally truncated ATGL mutants, which fail to localize to lipid droplets, translocate to the lipid droplet upon coexpression with G0S2, suggesting that G0S2 anchors ATGL to lipid droplets independent of ATGL's C-terminal lipid binding domain. Taken together, our results indicate that G0S2 also regulates human lipolysis by affecting enzyme activity and intracellular localization of ATGL. Increased lipolysis is known to contribute to the pathogenesis of insulin resistance, and G0S2 expression has been shown to be reduced in poorly controlled type 2 diabetic patients. Our data indicate that downregulation of G0S2 in adipose tissue could represent one of the underlying causes leading to increased lipolysis in the insulin-resistant state.

  16. Dietary CLA-induced lipolysis is delayed in soy oil-fed mice compared to coconut oil-fed mice.

    Science.gov (United States)

    Ippagunta, S; Angius, Z; Sanda, M; Barnes, K M

    2013-11-01

    Conjugated linoleic acid (CLA) has been shown to cause a reduction in obesity in several species. CLA-induced body fat loss is enhanced when mice are fed coconut oil (CO) and involves increased lipolysis. The objective of this paper was to determine if the CLA-induced lipolysis in mice fed with different oil sources was time-dependent. Mice were fed 7 % soybean oil (SO) or CO diets for 6 week and then supplemented with 0 or 0.5 % CLA for 3, 7, 10 or 14 days. Body fat and ex-vivo lipolysis was determined. Body fat was reduced by CO on day 7 (P Lipolysis was increased by CLA in CO-fed mice (P lipolysis in both CO- and SO-fed mice (P lipolysis and lipogenesis was determined by western blotting and real-time PCR, respectively. No significant differences were detected in protein expression. CO-fed mice had greater fatty acid synthase and stearyl CoA desaturase 1 mRNA expression and less acetyl CoA carboxylase mRNA expression (P lipolysis occurs more rapidly in CO vs SO-fed mice and lipogenesis is decreased in CO-fed mice with CLA supplementation.

  17. Amino acid-sensing mTOR signaling is involved in modulation of lipolysis by chronic insulin treatment in adipocytes.

    Science.gov (United States)

    Zhang, Chongben; Yoon, Mee-Sup; Chen, Jie

    2009-04-01

    Chronically high insulin levels and increased circulating free fatty acids released from adipose tissue through lipolysis are two features associated with insulin resistance. The relationship between chronic insulin exposure and adipocyte lipolysis has been unclear. In the present study we found that chronic insulin exposure in 3T3-L1 adipocytes, as well as in mouse primary adipocytes, increased basal lipolysis rates. This effect of insulin on lipolysis was only observed when the mammalian target of rapamycin (mTOR) pathway was inhibited by rapamycin in the adipocytes. In addition, amino acid deprivation in adipocytes phenocopied the effect of rapamycin in permitting the stimulation of lipolysis by chronic insulin exposure. The phosphatidylinositol 3-kinase-Akt pathway does not appear to be involved in this insulin effect. Furthermore, we found that triacylglycerol hydrolase (TGH) activity was required for the stimulation of lipolysis by combined exposure to insulin and rapamycin. Therefore, we propose that nutrient sufficiency, mediated by an mTOR pathway, suppresses TGH-dependent lipolysis stimulated by chronic insulin exposure in adipocytes.

  18. Natriuretic peptide-dependent lipolysis in fat cells is a primate specificity.

    Science.gov (United States)

    Sengenès, Coralie; Zakaroff-Girard, Alexia; Moulin, Agnès; Berlan, Michel; Bouloumié, Anne; Lafontan, Max; Galitzky, Jean

    2002-07-01

    We have recently demonstrated that natriuretic peptides (NPs), which are known for regulation of blood pressure via membrane guanylyl cyclase (GC) receptors, are lipolytic in human adipose tissue. In this study, we compared the NP control of lipolysis in adipocytes from humans, nonhuman primates (macaques), rodents (rats, mice, hamsters), and nonrodent mammals (rabbits, dogs). Isolated adipocytes from these species were exposed to increasing concentrations of atrial NP (ANP) or isoproterenol (beta-adrenergic agonist). Although isoproterenol was lipolytic in all of the species, ANP only enhanced lipolysis in human and macaque adipocytes. In primate fat cells, NP-induced lipolysis involved a cGMP-dependent pathway. Binding studies and real-time quantitative PCR assays revealed that rat adipocytes expressed a higher density of NP receptors compared with humans but with a different subtype pattern of expression; type-A GC receptors predominate in human fat cells. This was also confirmed by the weak GC-activity stimulation and the reduced cGMP formation under ANP exposure in rat adipocytes compared with human fat cells. In conclusion, NP-induced lipolysis is a primate specificity, and adipocytes from ANP-nonresponsive species present a predominance of "clearance" receptors and very low expression of "biologically active" receptors.

  19. Recent developments on lipolysis regulation in humans and discovery of a new lipolytic pathway.

    Science.gov (United States)

    Lafontan, M; Sengenes, C; Galitzky, J; Berlan, M; De Glisezinski, I; Crampes, F; Stich, V; Langin, D; Barbe, P; Rivière, D

    2000-11-01

    In man, the major hormones controlling the lipolytic function are insulin (inhibition of lipolysis) and catecholamines (stimulation of lipolysis). Catecholamines are of major importance for the regulation of lipid mobilization in human adipose tissue and for the increase of non-esterified fatty acid supply to the working muscle. In vitro studies have shown that there are differences in the catecholaminergic control of fat cells from various fat deposits and a number of physiological and pathological alterations of catecholamine-induced lipolysis have been reported. Lipolytic resistance to catecholamines has been reported in subcutaneous adipose tissue, the major fat depot in obese subjects. Multiple alterations in catecholamine signal transduction pathways have been reported. In situ microdialysis allows a physiological exploration of adipose tissue biology. Recent data obtained on the catecholaminergic regulation of lipolysis and lipid mobilization, using microdialysis in humans, will be analysed. A potent lipolytic and lipomobilizing effect of atrial natriuretic peptide has recently been discovered; the mechanisms of action and physiological relevance will also be discussed.

  20. Gelucire (R) 44/14 improves fat absorption in rats with impaired lipolysis

    NARCIS (Netherlands)

    Lukovac, S.; Gooijert, K. E. G.; Gregory, P. C.; Shlieout, G.; Stellaard, F.; Rings, E. H. H. M.; Verkade, H. J.

    2010-01-01

    Clinically relevant fat malabsorption is usually due to impaired intestinal fat digestion (lipolysis) and/or to impaired solubilization of the lipolytic metabolites. We hypothesized that Gelucire (R) 44/14 - a semi-solid self-micro-emulsifying excipient - could increase fat absorption. In relevant r

  1. Effect of exercise training on in vivo lipolysis in intra-abdominal adipose tissue in rats

    DEFF Research Database (Denmark)

    Enevoldsen, L H; Stallknecht, B; Fluckey, J D

    2000-01-01

    Intra-abdominal obesity is associated with cardiovascular disease and non-insulin-dependent diabetes mellitus, and physical training has been suggested to alleviate these conditions. We compared epinephrine-stimulated lipolysis in vivo in three intra-abdominal adipose tissues (ATs: retroperitoneal...

  2. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    OpenAIRE

    Schilling Brian K; Hammond Kelley G; Fisher-Wellman Kelsey H; Bloomer Richard J; Weber Adrianna A; Cole Bradford J

    2009-01-01

    Abstract Correction to Richard J Bloomer, Kelsey H Fisher-Wellman, Kelley G Hammond, Brian K Schilling, Adrianna A Weber and Bradford J Cole: Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men. Journal of the International Society of Sports Nutrition 2009, 6: 4

  3. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    Directory of Open Access Journals (Sweden)

    Schilling Brian K

    2009-04-01

    Full Text Available Abstract Correction to Richard J Bloomer, Kelsey H Fisher-Wellman, Kelley G Hammond, Brian K Schilling, Adrianna A Weber and Bradford J Cole: Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men. Journal of the International Society of Sports Nutrition 2009, 6: 4

  4. Characterization of murine melanocortin receptors mediating adipocyte lipolysis and examination of signalling pathways involved

    DEFF Research Database (Denmark)

    Møller, Cathrine Laustrup; Raun, Kirsten; Jacobsen, Marianne Lambert

    2011-01-01

    The melanocortin receptors (MCRs) belong to the G-protein coupled receptors (family A). So far, 5 different subtypes have been described (MC1R-MC5R) and of these MC2R and MC5R have been proposed to act directly in adipocytes and regulate lipolysis in rodents. Using ACTH and a-melanocyte stimulating...

  5. Major role of adipocyte prostaglandin E2 in lipolysis-induced macrophage recruitment[S

    Science.gov (United States)

    Hu, Xiaoqian; Cifarelli, Vincenza; Sun, Shishuo; Kuda, Ondrej; Abumrad, Nada A.; Su, Xiong

    2016-01-01

    Obesity induces accumulation of adipose tissue macrophages (ATMs), which contribute to both local and systemic inflammation and modulate insulin sensitivity. Adipocyte lipolysis during fasting and weight loss also leads to ATM accumulation, but without proinflammatory activation suggesting distinct mechanisms of ATM recruitment. We examined the possibility that specific lipid mediators with anti-inflammatory properties are released from adipocytes undergoing lipolysis to induce macrophage migration. In the present study, we showed that conditioned medium (CM) from adipocytes treated with forskolin to stimulate lipolysis can induce migration of RAW 264.7 macrophages. In addition to FFAs, lipolytic stimulation increased release of prostaglandin E2 (PGE2) and prostaglandin D2 (PGD2), reflecting cytosolic phospholipase A2 α activation and enhanced cyclooxygenase (COX) 2 expression. Reconstituted medium with the anti-inflammatory PGE2 potently induced macrophage migration while different FFAs and PGD2 had modest effects. The ability of CM to induce macrophage migration was abolished by treating adipocytes with the COX2 inhibitor sc236 or by treating macrophages with the prostaglandin E receptor 4 antagonist AH23848. In fasted mice, macrophage accumulation in adipose tissue coincided with increases of PGE2 levels and COX1 expression. Collectively, our data show that adipocyte-originated PGE2 with inflammation suppressive properties plays a significant role in mediating ATM accumulation during lipolysis. PMID:26912395

  6. Food-grade Micro-encapsulation Systems that May Induce Satiety via Delayed Lipolysis: A Review

    NARCIS (Netherlands)

    Corstens, M.N.; Berton-Carabin, C.C.; Vries, de R.J.; Troost, F.J.; Masclee, A.A.M.; Schroen, C.G.P.H.

    2017-01-01

    The increasing prevalence of overweight and obesity requires new, effective prevention and treatment strategies. One approach to reduce energy intake is by developing novel foods with increased satiating properties, which may be accomplished by slowing down lipolysis to deliver substrates to the ile

  7. Cyclopia maculata (honeybush tea) stimulates lipolysis in 3T3-L1 adipocytes.

    Science.gov (United States)

    Pheiffer, Carmen; Dudhia, Zulfaqar; Louw, Johan; Muller, Christo; Joubert, Elizabeth

    2013-10-15

    We have previously, for the first time, demonstrated that hot water extracts of Cyclopia maculata and Cyclopia subternata, endemic South African plants that are consumed as herbal teas, inhibit adipogenesis in 3T3-L1 adipocytes. The aim of this study was to extend the anti-obesity investigations of these plants by quantifying lipolysis in mature 3T3-L1 adipocytes. Glycerol concentration in culture supernatants was used as a marker of adipocyte lipolysis. Isoproterenol, a β-adrenergic agonist and a known lipolytic agent, was used as a positive control in our assays. Lipolysis was stimulated by all extracts, although statistical significance was noted for fermented (oxidised) C. maculata only. A concentration of 80μg/ml of C. maculata extract induced maximal lipolysis (1.8-fold, plipolysis was accompanied by an increase in the expression of hormone sensitive lipase (1.6-fold, plipolysis in mature 3T3-L1 adipocytes, providing further support for the anti-obesity effects of Cyclopia spp. Copyright © 2013 Elsevier GmbH. All rights reserved.

  8. Focused Ultrasound Lipolysis in the Treatment of Abdominal Cellulite: An Open-Label Study.

    Science.gov (United States)

    Moravvej, Hamideh; Akbari, Zahra; Mohammadian, Shahrzad; Razzaghi, Zahra

    2015-01-01

    Despite a growing popularity of noninvasive ultrasonic lipolysis procedure, there is a lack of evidence about the efficacy of this method. This study was performed to evaluate the efficacy of focused ultrasonic lipolysis on abdominal cellulite treatment. Twenty-eight consecutive subjects (age: 37.8 ± 8 years) underwent weekly transdermal focused ultrasonic lipolysis (Med Contour, General Project Ltd., Florence, Italy) and vacuum drainage for a maximum of eight sessions. Largest abdominal girth and 2 lines at 4 cm to 7 cm distance above and under it were located as fixed points of measurements. The mean value of the three fixed lines was considered as the abdominal circumference. Subjects were evaluated using measurements of circumference, immediately after and 3 weeks after the final treatment and compared using paired t test. One hundred ninety-four ultrasonic lipolysis procedures were performed on 28 subjects. A statistically significant (P cellulite, although some amount of circumference reduction reversal may be observed in long term follow-up visit.

  9. Effects of cortisol and growth hormone on lipolysis in human adipose tissue.

    Science.gov (United States)

    Ottosson, M; Lönnroth, P; Björntorp, P; Edén, S

    2000-02-01

    The in vitro effects of cortisol and GH on basal and stimulated lipolysis in human adipose tissue were studied using a tissue incubation technique. After preincubation for 3 days in control medium containing insulin, adipose tissue pieces were exposed to cortisol for 3 days. GH was added to the cortisol-containing medium during the last 24 h (day 6). Adipocytes were then isolated, and lipolysis was studied in the absence and presence of isoprenaline, noradrenaline, forskolin, and N-6-monobutyryl-cAMP. Cortisol reduced the basal rate of lipolysis (P cortisol-containing medium increased the basal rate of lipolysis (P effects were obtained in the presence of noradrenaline. Maximum forskolin-induced lipolytic activity was reduced after exposure of the tissue to cortisol (P effect (P cortisol and GH have opposite effects on the basal lipolytic activity in human adipose tissue in vitro as well as on the sensitivity to catecholamines, GH being the lipolytic and cortisol the antilipolytic agent. The present findings are in agreement with in vivo observations.

  10. Effects of morning rise in cortisol concentration on regulation of lipolysis in subcutaneous adipose tissue.

    Science.gov (United States)

    Samra, J S; Clark, M L; Humphreys, S M; Macdonald, I A; Matthews, D R; Frayn, K N

    1996-12-01

    Cortisol has a well-defined circadian rhythm. The aim of the study was to examine the effect of the morning rise in cortisol concentration on lipolysis in adipose tissue. Ten healthy subjects were studied on two occasions, and six of these were studied on three occasions. During the first two occasions, either a control or cortisol suppression study was performed by using metyrapone, and on the third occasion exogenous cortisol replacement was given in addition to metyrapone. Lipolysis in the subcutaneous adipose tissue of the anterior abdominal wall was studied by measurement of arteriovenous differences. Reduction in the early morning rise in cortisol led to significantly decreased venoarterialized differences for nonesterified fatty acids (P adipose tissue. At the same time the arterialized plasma triacylglycerol concentration increased (P adipose lipoprotein lipase (EC 3.1.1.34) rate of action (P effects on lipolysis. We conclude that the morning rise in plasma cortisol concentration plays an important role in the regulation of lipolysis in adipose tissue in normal healthy adults.

  11. Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise

    DEFF Research Database (Denmark)

    Stich, V; de Glisezinski, I; Berlan, M

    2000-01-01

    The goal of the study was to examine whether lipid mobilization from adipose tissue undergoes changes during repeated bouts of prolonged aerobic exercise. Microdialysis of the subcutaneous adipose tissue was used for the assessment of lipolysis; glycerol concentration was measured in the dialysate...

  12. Development of an Omnidirectional-Capable Electromagnetic Shock Wave Generator for Lipolysis

    Directory of Open Access Journals (Sweden)

    Ming Hau Chang

    2017-01-01

    Full Text Available Traditional methods for adipose tissue removal have progressed from invasive methods such as liposuction to more modern methods of noninvasive lipolysis. This research entails the development and evaluation of an omnidirectional-capable flat-coil electromagnetic shock wave generator (EMSWG for lipolysis. The developed EMSWG has the advantage of omnidirectional-capable operation. This capability increases the eventual clinical usability by adding three designed supports to the aluminum disk of the EMSWG to allow omnidirectional operation. The focal pressures of the developed EMSWG for different operating voltages were measured, and its corresponding energy intensities were calculated. The developed EMSWG was mounted in a downward orientation for lipolysis and evaluated as proof of concept. In vitro tests on porcine fatty tissues have been carried out. It is found that at a 6 kV operating voltage with 1500 shock wave exposures, a 2 cm thick subcutaneous hypodermis of porcine fatty tissue can be ruptured, resulting in a damaged area of 1.39 mm2. At a 6.5 kV operating voltage with 2000 shock wave exposures, the damaged area is increased to about 5.20 mm2, which can be enlarged by changing the focal point location, resulting in significant lipolysis for use in clinical applications.

  13. Lipolysis - a highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores.

    Science.gov (United States)

    Lass, Achim; Zimmermann, Robert; Oberer, Monika; Zechner, Rudolf

    2011-01-01

    Lipolysis is the biochemical pathway responsible for the catabolism of triacylglycerol (TAG) stored in cellular lipid droplets. The hydrolytic cleavage of TAG generates non-esterified fatty acids, which are subsequently used as energy substrates, essential precursors for lipid and membrane synthesis, or mediators in cell signaling processes. Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, it is most abundant, however, in white and brown adipose tissue. Over the last 5years, important enzymes and regulatory protein factors involved in lipolysis have been identified. These include an essential TAG hydrolase named adipose triglyceride lipase (ATGL) [annotated as patatin-like phospholipase domain-containing protein A2], the ATGL activator comparative gene identification-58 [annotated as α/β hydrolase containing protein 5], and the ATGL inhibitor G0/G1 switch gene 2. Together with the established hormone-sensitive lipase [annotated as lipase E] and monoglyceride lipase, these proteins constitute the basic "lipolytic machinery". Additionally, a large number of hormonal signaling pathways and lipid droplet-associated protein factors regulate substrate access and the activity of the "lipolysome". This review summarizes the current knowledge concerning the enzymes and regulatory processes governing lipolysis of fat stores in adipose and non-adipose tissues. Special emphasis will be given to ATGL, its regulation, and physiological function. Copyright © 2010 Elsevier Ltd. All rights reserved.

  14. Lipolysis – A highly regulated multi-enzyme complex mediates the catabolism of cellular fat stores

    Science.gov (United States)

    Lass, Achim; Zimmermann, Robert; Oberer, Monika; Zechner, Rudolf

    2011-01-01

    Summary Lipolysis is the biochemical pathway responsible for the catabolism of triacylglycerol (TAG) stored in cellular lipid droplets. The hydrolytic cleavage of TAG generates non-esterified fatty acids, which are subsequently used as energy substrates, essential precursors for lipid and membrane synthesis, or mediators in cell signaling processes. Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, it is most abundant, however, in white and brown adipose tissue. Over the last 5 years, important enzymes and regulatory protein factors involved in lipolysis have been identified. These include an essential TAG hydrolase named adipose triglyceride lipase (ATGL) [annotated as patatin-like phospholipase domain-containing protein A2], the ATGL activator comparative gene identification-58 [annotated as α/β hydrolase containing protein 5], and the ATGL inhibitor G0/G1 switch gene 2. Together with the established hormone-sensitive lipase [annotated as lipase E] and monoglyceride lipase, these proteins constitute the basic “lipolytic machinery”. Additionally, a large number of hormonal signaling pathways and lipid droplet-associated protein factors regulate substrate access and the activity of the “lipolysome”. This review summarizes the current knowledge concerning the enzymes and regulatory processes governing lipolysis of fat stores in adipose and non-adipose tissues. Special emphasis will be given to ATGL, its regulation, and physiological function. PMID:21087632

  15. Early B-cell Factor 1 Regulates Adipocyte Morphology and Lipolysis in White Adipose Tissue

    Science.gov (United States)

    Gao, Hui; Mejhert, Niklas; Fretz, Jackie A.; Arner, Erik; Lorente-Cebrián, Silvia; Ehrlund, Anna; Dahlman-Wright, Karin; Gong, Xiaowei; Strömblad, Staffan; Douagi, Iyadh; Laurencikiene, Jurga; Dahlman, Ingrid; Daub, Carsten O.; Rydén, Mikael; Horowitz, Mark C.; Arner, Peter

    2014-01-01

    Summary White adipose tissue (WAT) morphology characterized by hypertrophy (i.e. fewer but larger adipocytes) associates with increased adipose inflammation, lipolysis, insulin resistance and risk of diabetes. However, the causal relationships and the mechanisms controlling WAT morphology are unclear. Herein, we identified EBF1 as an adipocyte-expressed transcription factor with decreased expression/activity in WAT hypertrophy. In human adipocytes, the regulatory targets of EBF1 were enriched for genes controlling lipolysis and adipocyte morphology/differentiation and in both humans and murine models, reduced EBF1 levels associated with increased lipolysis and adipose hypertrophy. Although EBF1 did not affect adipose inflammation, TNFα reduced EBF1 gene expression. High fat diet-intervention in Ebf1+/− mice resulted in more pronounced WAT hypertrophy and attenuated insulin sensitivity compared with wild-type littermate controls. We conclude that EBF1 is an important regulator of adipose morphology and fat cell lipolysis and may constitute a link between WAT inflammation, altered lipid metabolism, adipose hypertrophy and insulin resistance. PMID:24856929

  16. Eicosapentaenoic acid inhibits tumour necrosis factor-α-induced lipolysis in murine cultured adipocytes.

    Science.gov (United States)

    Lorente-Cebrián, Silvia; Bustos, Matilde; Marti, Amelia; Fernández-Galilea, Marta; Martinez, J Alfredo; Moreno-Aliaga, Maria J

    2012-03-01

    Eicosapentaenoic acid (EPA) is an omega-3 polyunsaturated fatty acid with beneficial effects in obesity and insulin resistance. High levels of proinflammatory cytokine tumour necrosis factor-α (TNF-α) in obesity promote lipolysis in adipocytes, leading to the development of insulin resistance. Thus, the aims of the present study were to analyze the potential antilipolytic properties of EPA on cytokine-induced lipolysis and to investigate the possible mechanisms involved. The EPA effects on basal and TNF-α-induced lipolysis were determined in both primary rat and 3T3-L1 adipocytes. Treatment of primary rat adipocytes with EPA (100 and 200 μM) significantly decreased basal glycerol release (Plipolysis in a dose-dependent manner (Padipocytes. However, oral supplementation with EPA for 35 days was able to partially reverse the down-regulation of HSL and ATGL messenger RNA observed in retroperitoneal adipose tissue of high-fat-diet-fed rats. These findings suggest that EPA inhibits proinflammatory cytokine-induced lipolysis in adipocytes. This effect might contribute to explain the insulin-sensitizing properties of EPA. Copyright © 2012 Elsevier Inc. All rights reserved.

  17. Early B cell factor 1 regulates adipocyte morphology and lipolysis in white adipose tissue.

    Science.gov (United States)

    Gao, Hui; Mejhert, Niklas; Fretz, Jackie A; Arner, Erik; Lorente-Cebrián, Silvia; Ehrlund, Anna; Dahlman-Wright, Karin; Gong, Xiaowei; Strömblad, Staffan; Douagi, Iyadh; Laurencikiene, Jurga; Dahlman, Ingrid; Daub, Carsten O; Rydén, Mikael; Horowitz, Mark C; Arner, Peter

    2014-06-03

    White adipose tissue (WAT) morphology characterized by hypertrophy (i.e., fewer but larger adipocytes) associates with increased adipose inflammation, lipolysis, insulin resistance, and risk of diabetes. However, the causal relationships and the mechanisms controlling WAT morphology are unclear. Herein, we identified EBF1 as an adipocyte-expressed transcription factor with decreased expression/activity in WAT hypertrophy. In human adipocytes, the regulatory targets of EBF1 were enriched for genes controlling lipolysis and adipocyte morphology/differentiation, and in both humans and murine models, reduced EBF1 levels associated with increased lipolysis and adipose hypertrophy. Although EBF1 did not affect adipose inflammation, TNFα reduced EBF1 gene expression. High-fat diet intervention in Ebf1(+/-) mice resulted in more pronounced WAT hypertrophy and attenuated insulin sensitivity compared with wild-type littermate controls. We conclude that EBF1 is an important regulator of adipose morphology and fat cell lipolysis and may constitute a link between WAT inflammation, altered lipid metabolism, adipose hypertrophy, and insulin resistance. Copyright © 2014 Elsevier Inc. All rights reserved.

  18. Crotonis Fructus and Its Constituent, Croton Oil, Stimulate Lipolysis in OP9 Adipocytes

    Directory of Open Access Journals (Sweden)

    Mi-Seong Kim

    2014-01-01

    Full Text Available Introduction. Crotonis fructus (CF is the mature fruit of Croton tiglium L. and has been used for the treatment of gastrointestinal disturbance in Asia. It is well known that the main component of CF is croton oil (CO. The present study is to investigate the effects of CF extracts (CFE and CO on lipolysis in OP9 adipocytes. Methods. Glycerol release to the culture supernatants was used as a marker of adipocyte lipolysis. Results. Treatment with various concentrations of CFE and CO stimulates glycerol release in a dose-dependent manner. The increase in glycerol release by CFE is more potent than isoproterenol, which is a β-adrenergic agonist as a positive control in our system. The increased lipolysis by CFE and CO was accompanied by an increase of phosphorylated hormone sensitive lipase (pHSL but not nonphosphorylated HSL protein and mRNA. Pretreatment with H89, which is a protein kinase A inhibitor, significantly abolished the CFE- and CO-induced glycerol release in OP9 adipocytes. These results suggest that CFE and CO may be a candidate for the development of a lipolysis-stimulating agent in adipocytes.

  19. Food-grade Micro-encapsulation Systems that May Induce Satiety via Delayed Lipolysis: A Review

    NARCIS (Netherlands)

    Corstens, M.N.; Berton-Carabin, C.C.; Vries, de R.J.; Troost, F.J.; Masclee, A.A.M.; Schroen, C.G.P.H.

    2017-01-01

    The increasing prevalence of overweight and obesity requires new, effective prevention and treatment strategies. One approach to reduce energy intake is by developing novel foods with increased satiating properties, which may be accomplished by slowing down lipolysis to deliver substrates to the

  20. Inhibition of lipolysis in the novel transgenic quail model overexpressing G0/G1 switch gene 2 in the adipose tissue during feed restriction.

    Directory of Open Access Journals (Sweden)

    Sangsu Shin

    Full Text Available In addition to the issue of obesity in humans, the production of low-fat meat from domestic animals is important in the agricultural industry to satisfy consumer demand. Understanding the regulation of lipolysis in adipose tissue could advance our knowledge to potentially solve both issues. Although the G0/G1 switch gene 2 (G0S2 was recently identified as an inhibitor of adipose triglyceride lipase (ATGL in vitro, its role in vivo has not been fully clarified. This study was conducted to investigate the role of G0S2 gene in vivo by using two independent transgenic quail lines during different energy conditions. Unexpectedly, G0S2 overexpression had a negligible effect on plasma NEFA concentration, fat cell size and fat pad weight under ad libitum feeding condition when adipose lipolytic activity is minimal. A two-week feed restriction in non-transgenic quail expectedly caused increased plasma NEFA concentration and dramatically reduced fat cell size and fat pad weight. Contrary, G0S2 overexpression under a feed restriction resulted in a significantly less elevation of plasma NEFA concentration and smaller reductions in fat pad weights and fat cell size compared to non-transgenic quail, demonstrating inhibition of lipolysis and resistance to loss of fat by G0S2. Excessive G0S2 inhibits lipolysis in vivo during active lipolytic conditions, such as food restriction and fasting, suggesting G0S2 as a potential target for treatment of obesity. In addition, transgenic quail are novel models for studying lipid metabolism and mechanisms of obesity.

  1. Inhibition of lipolysis in the novel transgenic quail model overexpressing G0/G1 switch gene 2 in the adipose tissue during feed restriction.

    Science.gov (United States)

    Shin, Sangsu; Choi, Young Min; Han, Jae Yong; Lee, Kichoon

    2014-01-01

    In addition to the issue of obesity in humans, the production of low-fat meat from domestic animals is important in the agricultural industry to satisfy consumer demand. Understanding the regulation of lipolysis in adipose tissue could advance our knowledge to potentially solve both issues. Although the G0/G1 switch gene 2 (G0S2) was recently identified as an inhibitor of adipose triglyceride lipase (ATGL) in vitro, its role in vivo has not been fully clarified. This study was conducted to investigate the role of G0S2 gene in vivo by using two independent transgenic quail lines during different energy conditions. Unexpectedly, G0S2 overexpression had a negligible effect on plasma NEFA concentration, fat cell size and fat pad weight under ad libitum feeding condition when adipose lipolytic activity is minimal. A two-week feed restriction in non-transgenic quail expectedly caused increased plasma NEFA concentration and dramatically reduced fat cell size and fat pad weight. Contrary, G0S2 overexpression under a feed restriction resulted in a significantly less elevation of plasma NEFA concentration and smaller reductions in fat pad weights and fat cell size compared to non-transgenic quail, demonstrating inhibition of lipolysis and resistance to loss of fat by G0S2. Excessive G0S2 inhibits lipolysis in vivo during active lipolytic conditions, such as food restriction and fasting, suggesting G0S2 as a potential target for treatment of obesity. In addition, transgenic quail are novel models for studying lipid metabolism and mechanisms of obesity.

  2. Synbiotic food consumption reduces levels of triacylglycerols and VLDL, but not cholesterol, LDL, or HDL in plasma from pregnant women.

    Science.gov (United States)

    Taghizadeh, Mohsen; Hashemi, Teibeh; Shakeri, Hossein; Abedi, Fatemeh; Sabihi, Sima-Sadat; Alizadeh, Sabihe-Alsadat; Asemi, Zatolla

    2014-02-01

    To our knowledge, no reports are available indicating the effects of synbiotic food consumption on blood lipid profiles and biomarkers of oxidative stress among pregnant women. This study was conducted to evaluate the effects of daily consumption of a synbiotic food on blood lipid profiles and biomarkers of oxidative stress in pregnant women. This randomized, double-blind, controlled clinical trial was performed among 52 primigravida pregnant women, aged 18 to 35-year-old at their third trimester. After a 2-week run-in period, subjects were randomly assigned to consume either a synbiotic (n = 26) or control food (n = 26) for 9 weeks. The synbiotic food consisted of a probiotic viable and heat-resistant Lactobacillus sporogenes (1 × 10⁷ CFU) and 0.04 g inulin (HPX)/g as the prebiotic. Patients were asked to consume the synbiotic and control foods two times a day. Biochemical measurements including blood lipid profiles, plasma total antioxidant capacity (TAC) and total glutathione (GSH) were conducted before and after 9 weeks of intervention. Consumption of a synbiotic food for 9 weeks resulted in a significant reduction in serum TAG (P = 0.04), VLDL (P = 0.04) and a significant rise in plasma GSH levels (P = 0.004) compared to the control food. No significant effects of the synbiotic food consumption on serum TC, LDL, HDL and plasma TAC levels (P > 0.05) were observed. Trial registry code: http://www.irct.ir . IRCT201212105623N3.

  3. Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty diet induced obese mice.

    Science.gov (United States)

    Geng, Bin; Cai, Bo; Liao, Feng; Zheng, Yang; Zeng, Qiang; Fan, Xiaofang; Gong, Yongsheng; Yang, Jichun; Cui, Qing Hua; Tang, Chaoshu; Xu, Guo Heng

    2013-01-01

    Adipose tissue expressed endogenous cystathionine gamma lyase (CSE)/hydrogen sulfide (H2S) system. H2S precursor inhibited catecholamine stimulated lipolysis. Thus, we hypothesized that CSE/H2S system regulates lipolysis which contributed to the pathogenesis of insulin resistance. We treated rat adipocyte with DL-propargylglycine (PAG, a CSE inhibitor), L-cysteine (an H2S precursor) plus pyridoxial phosphate (co-enzyme) or the H2S chronic release donor GYY4137, then the glycerol level was assayed for assessing the lipolysis. Then, the effects of PAG and GYY4137 on insulin resistance in high fatty diet (HFD) induced obese mice were investigated. Here, we found that PAG time-dependently increased basal or isoproterenol stimulated lipolysis. However, L-cysteine plus pyridoxial phosphate or GYY4137 significantly reduced it. PAG increased phosphorylated protein kinase A substrate, perilipin 1 and hormone sensitive lipase, but L-cysteine and GYY4137 decreased the parameters. In HFD induced obese mice, PAG increased adipose basal lipolysis, thus blunted fat mass increase, resulting in lowering insulin resistance evidenced by reduction of fasting glucose, insulin level, HOMA index, oral glucose tolerance test (OGTT) curve area and elevating the insulin tolerance test (ITT) response. GYY4137 inhibited lipolysis in vivo without increasing fat mass, but also ameliorated the insulin resistance in HFD mice. These results implicated that inhibition endogenous CSE/H2S system in adipocytes increased lipolysis by a protein kinase A-perilipin/hormone-sensitive lipase pathway, thus blunted fat mass increase and reduced insulin resistance in obese mice; giving H2S donor decreased lipolysis, also reduced insulin resistance induced by HFD. Our data showed that increase or decrease H2S induced opposite lipolysis, but had the same effect on insulin resistance. The paradoxical regulation may be resulted from different action of H2S on metabolic and endocrine function in adipocyte.

  4. Increase or decrease hydrogen sulfide exert opposite lipolysis, but reduce global insulin resistance in high fatty diet induced obese mice.

    Directory of Open Access Journals (Sweden)

    Bin Geng

    Full Text Available OBJECTIVE: Adipose tissue expressed endogenous cystathionine gamma lyase (CSE/hydrogen sulfide (H2S system. H2S precursor inhibited catecholamine stimulated lipolysis. Thus, we hypothesized that CSE/H2S system regulates lipolysis which contributed to the pathogenesis of insulin resistance. METHODS: We treated rat adipocyte with DL-propargylglycine (PAG, a CSE inhibitor, L-cysteine (an H2S precursor plus pyridoxial phosphate (co-enzyme or the H2S chronic release donor GYY4137, then the glycerol level was assayed for assessing the lipolysis. Then, the effects of PAG and GYY4137 on insulin resistance in high fatty diet (HFD induced obese mice were investigated. RESULTS: Here, we found that PAG time-dependently increased basal or isoproterenol stimulated lipolysis. However, L-cysteine plus pyridoxial phosphate or GYY4137 significantly reduced it. PAG increased phosphorylated protein kinase A substrate, perilipin 1 and hormone sensitive lipase, but L-cysteine and GYY4137 decreased the parameters. In HFD induced obese mice, PAG increased adipose basal lipolysis, thus blunted fat mass increase, resulting in lowering insulin resistance evidenced by reduction of fasting glucose, insulin level, HOMA index, oral glucose tolerance test (OGTT curve area and elevating the insulin tolerance test (ITT response. GYY4137 inhibited lipolysis in vivo without increasing fat mass, but also ameliorated the insulin resistance in HFD mice. CONCLUSION: These results implicated that inhibition endogenous CSE/H2S system in adipocytes increased lipolysis by a protein kinase A-perilipin/hormone-sensitive lipase pathway, thus blunted fat mass increase and reduced insulin resistance in obese mice; giving H2S donor decreased lipolysis, also reduced insulin resistance induced by HFD. Our data showed that increase or decrease H2S induced opposite lipolysis, but had the same effect on insulin resistance. The paradoxical regulation may be resulted from different action of H2S on

  5. Conjugated linoleic acid supplementation caused reduction of perilipin1 and aberrant lipolysis in epididymal adipose tissue

    Energy Technology Data Exchange (ETDEWEB)

    Cai, Demin [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Li, Hongji [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhou, Bo [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Han, Liqiang [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Zhang, Xiaomei [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoyu, E-mail: haubiochem@163.com [Key Laboratory of Animal Biochemistry and Nutrition, Ministry of Agriculture, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China); Yang, Guoqing, E-mail: gqyang@yeah.net [College of Animal Sciences and Veterinary Medicine, Henan Agricultural University, Zhengzhou 450002, Henan Province, People' s Republic of China (China)

    2012-06-15

    Highlights: Black-Right-Pointing-Pointer Conjugated linoleic acid supplementation suppresses perilipin1 in epididymal fat. Black-Right-Pointing-Pointer Conjugated linoleic acid inhibits promoter activity of perilipin1 in 3T3-L1 cells. Black-Right-Pointing-Pointer Conjugated linoleic acids elevate basal but blunt hormone-stimulated lipolysis. -- Abstract: Perilipin1, a coat protein of lipid droplet, plays a key role in adipocyte lipolysis and fat formation of adipose tissues. However, it is not clear how the expression of perilipin1 is affected in the decreased white adipose tissues (WAT) of mice treated with dietary supplement of conjugated linoleic acids (CLA). Here we obtained lipodystrophic mice by dietary administration of CLA which exhibited reduced epididymal (EPI) WAT, aberrant adipocytes and decreased expression of leptin in this tissue. We found both transcription and translation of perilipin1 was suppressed significantly in EPI WAT of CLA-treated mice compared to that of control mice. The gene expression of negative regulator tumor necrosis factor {alpha} (TNF{alpha}) and the positive regulator Peroxisome Proliferator-Activated Receptor-{gamma} (PPAR{gamma}) of perilipin1 was up-regulated and down-regulated, respectively. In cultured 3T3-L1 cells the promoter activity of perilipin1 was dramatically inhibited in the presence of CLA. Using ex vivo experiment we found that the basal lipolysis was elevated but the hormone-stimulated lipolysis blunted in adipose explants of CLA-treated mice compared to that of control mice, suggesting that the reduction of perilipin1 in white adipose tissues may at least in part contribute to CLA-mediated alternation of lipolysis of WAT.

  6. Monoacyl phosphatidylcholine inhibits the formation of lipid multilamellar structures during in vitro lipolysis of self-emulsifying drug delivery systems

    DEFF Research Database (Denmark)

    Tran, Thuy; Siqueira, Scheyla D V S; Amenitsch, Heinz

    2016-01-01

    The colloidal structures formed during lipolysis of self-emulsifying drug delivery systems (SEDDS) might affect the solubilisation and possibly the absorption of drugs. The aim of the current study is to elucidate the structures formed during the in vitro lipolysis of four SEDDS containing medium....... However, SEDDS containing 20-30% w/w MAPC did not form MLS during the lipolysis. The cryo-TEM and DLS studies showed that MAPC-free SEDDS formed coarse emulsions while MAPC-containing SEDDS formed nanoemulsions during the dispersion in digestion medium. From the first minute and during the entire...

  7. Acute reduction of lipolysis reduces adiponectin and IL-18:evidence from an intervention study with acipimox and nsulin

    DEFF Research Database (Denmark)

    Lindegaard, B.; Ditlevsen, Susanne; Plomgaard, P.;

    2013-01-01

    and plasma IL-18 were reduced during both situations where lipolysis was inhibited (p TNF-α did not change during low NEFA concentrations...... assessed whether (1) overnight administration of a low dose of acipimox and/or (2) insulin-induced suppression of NEFA flux altered circulating plasma levels of adiponectin, IL-18, TNF-α and IL-6 in the basal condition and in a two-stage euglycaemic–hyperinsulinaemic clamp combined with stable isotopes....... Conclusions/interpretation Using two different tools to manipulate lipolysis, the present study found that acute inhibition of lipolysis reduces levels of adiponectin and IL-18 in patients with HIV-associated lipodystrophy....

  8. Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome.

    Science.gov (United States)

    Langin, Dominique

    2006-06-01

    Adipose tissue lipolysis is the catabolic process leading to the breakdown of triglycerides stored in fat cells and release of fatty acids and glycerol. Recent work has revealed that lipolysis is not a simple metabolic pathway stimulated by catecholamines and inhibited by insulin. There have been new discoveries on the endocrine and paracrine regulation of lipolysis and on the molecular mechanisms of triglyceride hydrolysis. Catecholamines modulate lipolysis through lipolytic beta-adrenoceptor and antilipolytic alpha2-adrenoceptor. Recent studies have allowed a better understanding of the relative contribution of the two types of receptors and provided evidence for the in vivo involvement of alpha2-adrenoceptors in the physiological control of subcutaneous adipose tissue lipolysis. A puzzling observation is the characterization of a residual catecholamine-induced lipolysis in mice deficient in beta-adrenoceptors. A novel lipolytic system has been characterized in human fat cells. Natriuretic peptides stimulate lipolysis through a cGMP-dependent pathway. There are other lipolytic pathways active in human fat cells which importance is not fully understood. Forty years after the description of the antilipolytic effect of nicotinic acid, the receptors have been identified. Adrenomedullin which is produced by adipocytes exert an antilipolytic effect through an indirect mechanism involving nitric oxide. The molecular details of the lipolytic reaction are not fully understood. The role of the lipases has been re-evaluated with the cloning of adipose triglyceride lipase. Hormone-sensitive lipase appears as the major lipase for catecholamine and natriuretic peptide-stimulated lipolysis whereas adipose triglyceride lipase mediates the hydrolysis of triglycerides during basal lipolysis. Translocation of hormone-sensitive lipase bound to the adipocyte lipid binding protein to the lipid droplet seems to be an important step during lipolytic activation. Re-organization of the

  9. Dietary supplement increases plasma norepinephrine, lipolysis, and metabolic rate in resistance trained men

    Directory of Open Access Journals (Sweden)

    Schilling Brian K

    2009-01-01

    Full Text Available Abstract Background Dietary supplements targeting fat loss and increased thermogenesis are prevalent within the sport nutrition/weight loss market. While some isolated ingredients have been reported to be efficacious when used at high dosages, in particular in animal models and/or via intravenous delivery, little objective evidence is available pertaining to the efficacy of a finished product taken by human subjects in oral form. Moreover, many ingredients function as stimulants, leading to increased hemodynamic responses. The purpose of this investigation was to determine the effects of a finished dietary supplement on plasma catecholamine concentration, markers of lipolysis, metabolic rate, and hemodynamics. Methods Ten resistance trained men (age = 27 ± 4 yrs; BMI = 25 ± 3 kg· m-2; body fat = 9 ± 3%; mean ± SD ingested a dietary supplement (Meltdown®, Vital Pharmaceuticals or a placebo, in a random order, double blind cross-over design, with one week separating conditions. Fasting blood samples were collected before, and at 30, 60, and 90 minutes post ingestion and were assayed for epinephrine (EPI, norepinephrine (NE, glycerol, and free fatty acids (FFA. Area under the curve (AUC was calculated for all variables. Gas samples were collected from 30–60 minutes post ingestion for measurement of metabolic rate. Heart rate and blood pressure were recorded at all blood collection times. Results AUC was greater for the dietary supplement compared to the placebo for NE (1332 ± 128 pg·mL-1·90 min-1 vs. 1003 ± 133 pg·mL-1·90 min-1; p = 0.03, glycerol (44 ± 3 μg·mL-1·90 min-1 vs. 26 ± 2 μg·mL-1·90 min-1; p -1·90 min-1 vs. 0.88 ± 0.12 mmol·L-1·90 min-1; p = 0.0003. No difference between conditions was noted for EPI AUC (p > 0.05. For all variables, values were highest at 90 minutes post ingestion. Total kilocalorie expenditure during the 30 minute collection period was 29.6% greater (p = 0.02 for the dietary supplement (35 ± 3

  10. Genetic variants of adiponectin receptor 2 are associated with increased adiponectin levels and decreased triglyceride/VLDL levels in patients with metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Göke Burkhard

    2006-05-01

    Full Text Available Abstract Background Adiponectin acts as an antidiabetic, antiinflammatory and antiatherogenic adipokine. These effects are assumed to be mediated by the recently discovered adiponectin receptors AdipoR1 and AdipoR2. Aim The purpose of this study was to determine whether variations in the AdipoR1 and AdipoR2 genes may contribute to insulin resistance, dyslipidemia and inflammation. Methods We sequenced all seven coding exons of both genes in 20 unrelated German subjects with metabolic syndrome and tested genetic variants for association with glucose, lipid and inflammatory parameters. Results We identified three AdipoR2 variants (+795G/A, +870C/A and +963C/T in perfect linkage disequilibrium (r2 = 1 with a minor allele frequency of 0.125. This haplotype was associated with higher plasma adiponectin levels and decreased fasting triglyceride, VLDL-triglyceride and VLDL-cholesterol levels. No association, however, was observed between the AdipoR2 SNP cluster and glucose metabolism. Conclusion To our knowledge, this is the first study to identify an association between genetic variants of the adiponectin receptor genes and plasma adiponectin levels. Furthermore, our data suggest that AdipoR2 may play an important role in triglyceride/VLDL metabolism.

  11. Softness of atherogenic lipoproteins: a comparison of very low density lipoprotein (VLDL) and low density lipoprotein (LDL) using elastic incoherent neutron scattering (EINS).

    Science.gov (United States)

    Mikl, Christian; Peters, Judith; Trapp, Marcus; Kornmueller, Karin; Schneider, Wolfgang J; Prassl, Ruth

    2011-08-31

    Apolipoprotein B100 (apoB100)-containing plasma lipoproteins (LDL and VLDL) supply tissues and cells with cholesterol and fat. During lipolytic conversion from VLDL to LDL the size and chemical composition of the particles change, but the apoB100 molecule remains bound to the lipids and regulates the receptor mediated uptake. The molecular physical parameters which control lipoprotein remodeling and enable particle stabilization by apoB100 are largely unknown. Here, we have compared the molecular dynamics and elasticities of VLDL and LDL derived by elastic neutron scattering temperature scans. We have determined thermal motions, dynamical transitions, and molecular fluctuations, which reflect the temperature-dependent motional coupling between lipid and protein. Our results revealed that lipoprotein particles are extremely soft and flexible. We found substantial differences in the molecular resiliences of lipoproteins, especially at higher temperatures. These discrepancies not only can be explained in terms of lipid composition and mobility but also suggest that apoB100 displays different dynamics dependent on the lipoprotein it is bound to. Hence, we suppose that the inherent conformational flexibility of apoB100 permits particle stabilization upon lipid exchange, whereas the dynamic coupling between protein and lipids might be a key determinant for lipoprotein conversion and atherogenicity.

  12. Post-exercise abdominal, subcutaneous adipose tissue lipolysis in fasting subjects is inhibited by infusion of the somatostatin analogue octreotide

    DEFF Research Database (Denmark)

    Enevoldsen, Lotte H; Polak, Jan; Simonsen, Lene

    2007-01-01

    .c., abdominal adipose tissue metabolism, before, during and after exercise in healthy, fasting, young male subjects. The adipose tissue net releases of fatty acids and glycerol were measured by arterio-venous catheterizations and simultaneous measurements of adipose tissue blood flow with the local Xe....... The results show that octreotide infusion during rest increased lipolysis and fatty acid release from the abdominal, s.c. adipose tissue. The exercise-induced increase in lipolysis and fatty acid release does not seem to be affected by octreotide when compared with the control study without octreotide...... infusion while the post-exercise increase in lipolysis is inhibited by octreotide, suggesting that the exercise-induced increase in GH secretion plays a role for the post-exercise lipolysis in s.c., abdominal adipose tissue....

  13. Increased lipolysis but diminished gene expression of lipases in subcutaneous adipose tissue of healthy young males with intrauterine growth retardation

    DEFF Research Database (Denmark)

    Højbjerre, Lise; Alibegovic, Amra C; Sonne, Mette P

    2011-01-01

    ) and femoral (SCFAT) adipose tissue. Additionally, mRNA expression of lipases was evaluated in biopsies from SCAAT. Lipolysis in SCAAT was substantially higher in IUGR than in CON subjects despite markedly lower mRNA expression of lipases. Blood flow was higher in IUGR compared with CON in both SCAAT and SCFAT...... are characterized by increased in vivo adipose tissue lipolysis and blood flow with a paradoxically decreased expression of lipases compared with CON, and 10 days of physical inactivity underlined the baseline findings. Subjects with IUGR exhibit primary defects in adipose tissue metabolism........ Whole body insulin sensitivity did not differ between groups and decreased after bed rest. After bed rest, SCAAT lipolysis remained higher in IUGR compared with CON, and SCFAT lipolysis decreased in CON but not in IUGR. Prior to the development of whole body insulin resistance, young men with IUGR...

  14. Immunogenic inhibition of prominent ruminal bacteria as a means to reduce lipolysis and biohydrogenation activity in vitro

    Science.gov (United States)

    Through the microbial processes of lipolysis and biohydrogenation, ruminal animals promote the accumulation of saturated fatty acids in their meat and milk. Anaerovibrio lipolyticus, Butyrivibrio fibrisolvens, and Propionibacterium avidum and acnes have been identified as contributors to ruminal li...

  15. Effects of local alpha2-adrenergic receptor blockade on adipose tissue lipolysis during prolonged systemic adrenaline infusion in normal man

    DEFF Research Database (Denmark)

    Simonsen, Lene; Enevoldsen, Lotte H; Stallknecht, Bente

    2008-01-01

    During prolonged adrenaline infusion, lipolysis peaks within 30 min and thereafter tends to decline, and we hypothesized that the stimulation of local adipose tissue alpha2-adrenergic receptors accounts for this decline. The lipolytic effect of a prolonged intravenous adrenaline infusion combined....... Regional adipose tissue blood flow was measured by the (133)Xe clearance technique. Regional glycerol output (lipolytic rate) was calculated from these measurements and simultaneous measurements of arterial glycerol concentrations. Adrenaline infusion increased lipolysis in all three depots (data...... circulating adrenaline concentrations, and the decrease in lipolysis in subcutaneous adipose tissue under prolonged adrenaline stimulation is thus not attributed to alpha2-adrenergic receptor inhibition of lipolysis. However, in the preperitoneal adipose tissue depot, alpha2-adrenergic receptor tone plays...

  16. Decrease in hepatic very-low-density lipoprotein-triglyceride secretion after weight loss is inversely associated with changes in circulating leptin.

    Science.gov (United States)

    Magkos, F; Fabbrini, E; McCrea, J; Patterson, B W; Eagon, J C; Klein, S

    2010-07-01

    Although weight loss usually decreases very-low-density lipoprotein-triglyceride (VLDL-TG) secretion rate, the change in VLDL-TG kinetics is not directly related to the change in body weight. Circulating leptin also declines with weight loss and can affect hepatic lipid metabolism. The aim of this study was to determine whether circulating leptin is associated with weight loss-induced changes in VLDL-TG secretion. Ten extremely obese subjects were studied. VLDL-TG secretion rate and the contribution of systemic (derived from lipolysis of subcutaneous adipose tissue TG) and non-systemic fatty acids (derived primarily from lipolysis of intrahepatic and intraperitoneal TG, and de novo lipogenesis) to VLDL-TG production were determined by using stable isotopically labelled tracer methods before and 1 year after gastric bypass surgery. Subjects lost 33 +/- 12% of body weight, and VLDL-TG secretion rate decreased by 46 +/- 23% (p = 0.001), primarily because of a decrease in the secretion of VLDL-TG from non-systemic fatty acids (p = 0.002). Changes in VLDL-TG secretion rates were not significantly related to reductions in body weight, body mass index, plasma palmitate flux, free fatty acid or insulin concentrations. The change in VLDL-TG secretion was inversely correlated with the change in plasma leptin concentration (r = -0.72, p = 0.013), because of a negative association between changes in leptin and VLDL-TG secretion from non-systemic fatty acids (r = -0.95, p Weight loss-induced changes in plasma leptin concentration are inversely associated with changes in VLDL-TG secretion rate. Additional studies are needed to determine whether the correlation between circulating leptin and VLDL-TG secretion represents a cause-and-effect relationship.

  17. Both inflammatory and classical lipolytic pathways are involved in lipopolysaccharide-induced lipolysis in human adipocytes.

    Science.gov (United States)

    Grisouard, Jean; Bouillet, Elisa; Timper, Katharina; Radimerski, Tanja; Dembinski, Kaethi; Frey, Daniel M; Peterli, Ralph; Zulewski, Henryk; Keller, Ulrich; Müller, Beat; Christ-Crain, Mirjam

    2012-02-01

    High fat diet-induced endotoxaemia triggers low-grade inflammation and lipid release from adipose tissue. This study aims to unravel the cellular mechanisms leading to the lipopolysaccharide (LPS) effects in human adipocytes. Subcutaneous pre-adipocytes surgically isolated from patients were differentiated into mature adipocytes in vitro. Lipolysis was assessed by measurement of glycerol release and mRNA expression of pro-inflammatory cytokines were evaluated by real-time PCR. Treatment with LPS for 24 h induced a dose-dependent increase in interleukin (IL)-6 and IL-8 mRNA expression. At 1 µg/ml LPS, IL-6 and IL-8 were induced to 19.5 ± 1.8-fold and 662.7 ± 91.5-fold (P < 0.01 vs basal), respectively. From 100 ng/ml to 1 µg/ml, LPS-induced lipolysis increased to a plateau of 3.1-fold above basal level (P < 0.001 vs basal). Co-treatment with inhibitors of inhibitory kappa B kinase kinase beta (IKKβ) or NF-κB inhibited LPS-induced glycerol release. Co-treatment with the protein kinase A (PKA) inhibitor H-89, the lipase inhibitor orlistat or the hormone-sensitive lipase (HSL) inhibitor CAY10499 abolished the lipolytic effects of LPS. Co-treatment with the MAPK inhibitor, U0126 also reduced LPS-induced glycerol release. Inhibition of lipolysis by orlistat or CAY10499 reduced LPS-induced IL-6 and IL-8 mRNA expression. Induction of lipolysis by the synthetic catecholamine isoproterenol or the phosphodiesterase type III inhibitor milrinone did not alter basal IL-6 and IL-8 mRNA expression after 24 treatments whereas these compounds enhanced LPS-induced IL-6 and IL-8 mRNA expression. Both the inflammatory IKKβ/NF-κB pathway and the lipolytic PKA/HSL pathways mediate LPS-induced lipolysis. In turn, LPS-induced lipolysis reinforces the expression of pro-inflammatory cytokines and, thereby, triggers its own lipolytic activity.

  18. Endothelin-1 stimulates human adipocyte lipolysis through the ET A receptor.

    Science.gov (United States)

    Eriksson, A K S; van Harmelen, V; Stenson, B M; Aström, G; Wåhlén, K; Laurencikiene, J; Rydén, M

    2009-01-01

    Levels of the vascular peptide endothelin-1 (ET-1) are significantly elevated in obesity. Adipose tissue-derived ET-1 attenuates insulin-mediated antilipolysis in human visceral adipocytes through the activation of the ET receptor B (ET(B)R), thereby linking ET-1 to insulin resistance. Whether ET-1 has direct effects on lipolysis in human adipocytes is not known. Endothelin-1 receptor (ETR) mRNA expression was determined by quantitative PCR in 130 non-obese and obese subjects. ET-1 mRNA in different adipose tissue regions was also assessed. ETR protein expression was analyzed by western blotting in 37 subjects. The effect of ET-1 on lipolysis was assessed in freshly isolated adipocytes and in vitro differentiated adipocytes from human donors. Freshly isolated human adipocytes incubated with different concentrations of ET-1 showed no acute effect on lipolysis. In contrast, a 24 h incubation in primary cultures of human adipocytes resulted in a significant 50% increase in lipolysis. This effect was concentration dependent and could be mimicked by an agonist of the ET(A) receptor but not with a selective ET(B)R agonist. Adipocyte differentiation was not affected by any of the agonists. In subcutaneous (s.c.) adipose tissue from 19 non-obese and 18 obese subjects, the protein expression of ET(A)R was significantly higher in obese subjects whereas there was no difference in ET(B)R expression. Interestingly, the differences in protein expression were not observed at the mRNA level as ET(A)R expression was similar between lean and obese subjects. Long-term but not acute incubation of human adipocytes with ET-1 results in a significant increase in lipolysis. This appears to be mediated through the activation of ET(A)R, demonstrating a yet another receptor-specific effect of ET-1. In addition, the protein expression of ET(A)R is increased in s.c. adipose tissue in obesity, possibly through post-transcriptional mechanisms. An increased effect of ET-1 could be a mechanism

  19. Novel pharmacological probes reveal ABHD5 as a locus of lipolysis control in white and brown adipocytes.

    Science.gov (United States)

    Rondini, Elizabeth A; Mladenovic-Lucas, Ljiljana; Roush, William R; Halvorsen, Geoff; Green, Alex E; Granneman, James G

    2017-09-19

    Current knowledge regarding acute regulation of adipocyte lipolysis is largely based on receptor-mediated activation or inhibition of pathways that influence intracellular levels of cyclic AMP (cAMP), thereby affecting protein kinase A (PKA) activity. We recently identified synthetic ligands of α-β-hydrolase domain containing 5 (ABHD5) that directly activate adipose triglyceride lipase (ATGL) by dissociating ABHD5 from its inhibitory regulator, perilipin-1 (PLIN1). In the current study we used these novel ligands to determine the direct contribution of ABHD5 to various aspects of lipolysis control in white (3T3-L1) and brown adipocytes. ABHD5 ligands stimulated adipocyte lipolysis without affecting PKA-dependent phosphorylation on consensus sites of PLIN1 or HSL. Co-treatment of adipocytes with synthetic ABHD5 ligands did not alter the potency or maximal lipolysis efficacy of the β-adrenergic receptor (ADRB) agonist, isoproterenol, indicating both target a common pool of ABHD5. Reducing ADRB/PKA signaling with insulin or desensitizing ADRB suppressed lipolysis responses to a subsequent challenge with ISO, but not to ABHD5 ligands. Lastly, despite strong treatment differences in PKA-dependent phosphorylation of hormone sensitive lipase (HSL), we found that ligand-mediated activation of ABHD5 led to complete TG hydrolysis, which involved predominately ATGL, but also HSL. These results indicate that the overall pattern of lipolysis controlled by ABHD5 ligands is similar to that of isoproterenol and that ABHD5 plays a central role in the regulation of adipocyte lipolysis. As lipolysis is critical for adaptive thermogenesis and in catabolic tissue remodeling, ABHD5 ligands may provide a means of activating these processes under conditions where receptor signaling is compromised. The American Society for Pharmacology and Experimental Therapeutics.

  20. Assessment of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model.

    Science.gov (United States)

    Ibrahim, Fady; Gershkovich, Pavel; Sivak, Olena; Wasan, Ellen K; Wasan, Kishor M

    2012-08-15

    The purpose of this study was to investigate the intraluminal processing of novel oral lipid-based formulations of amphotericin B using an in vitro lipolysis model. Amphotericin B (AmB) was formulated in three lipid-based formulations consisting of different lipid components: iCo-009, iCo-010 and iCo-011. Various lipid loads (0.25, 0.5, 1 and 2 g) were digested using the lipolysis model to assess AmB distribution among the lipolysis phases. The duration of lipolysis was comparable among the three formulations except for 2 g load of iCo-009 which had a significantly longer lipolysis than iCo-010 and iCo-011. The lipid components of iCo-009 experienced lower extent of lipolysis as compared to other formulations. Amphotericin B concentration in the aqueous phases was the highest with iCo-010 which also had the lowest sediment recovery. Amphotericin B levels in the undigested lipid layers were comparable between iCo-009 and iCo-010 and were higher than with iCo-011. Given the observation that iCo-010 had the highest aqueous micellar solubilization and the lowest sediment recovery of AmB among the tested formulations, these results could potentially be used to interpret and predict the in vivo performance of AmB- SEDDS formulations in future studies. Crown Copyright © 2012. Published by Elsevier B.V. All rights reserved.

  1. Glucocorticoids antagonize tumor necrosis factor-α-stimulated lipolysis and resistance to the antilipolytic effect of insulin in human adipocytes.

    Science.gov (United States)

    Lee, Mi-Jeong; Fried, Susan K

    2012-11-01

    High concentrations of TNF within obese adipose tissue increase basal lipolysis and antagonize insulin signaling. Adipocytes of the obese are also exposed to elevated levels of glucocorticoids (GCs), which antagonize TNF actions in many cell types. We tested the hypothesis that TNF decreases sensitivity to the antilipolytic effect of insulin and that GCs antagonize this effect in differentiated human adipocytes. Lipolysis and expression levels of lipolytic proteins were measured after treating adipocytes with TNF, dexamethasone (DEX), or DEX + TNF for up to 48 h. TNF not only increased basal lipolysis, it caused resistance to the antilipolytic effects of insulin in human adipocytes. DEX alone did not significantly affect lipolysis. Cotreatment with DEX blocked TNF induction of basal lipolysis and insulin resistance by antagonizing TNF stimulation of PKA-mediated phosphorylation of hormone-sensitive lipase (HSL) at Ser⁵⁶³ and Ser⁶⁶⁰ and perilipin. TNF did not affect perilipin, HSL, or phosphodiesterase-3B mass but paradoxically suppressed adipose tissue triglyceride lipase expression, and this effect was blocked by DEX. The extent to which GCs can restrain the lipolytic actions of TNF may both diminish the potentially deleterious effects of excess lipolysis and contribute to fat accumulation in obesity.

  2. In preeclampsia, maternal third trimester subcutaneous adipocyte lipolysis is more resistant to suppression by insulin than in healthy pregnancy.

    Science.gov (United States)

    Huda, Shahzya S; Forrest, Rachel; Paterson, Nicole; Jordan, Fiona; Sattar, Naveed; Freeman, Dilys J

    2014-05-01

    Obesity increases preeclampsia risk, and maternal dyslipidemia may result from exaggerated adipocyte lipolysis. We compared adipocyte function in preeclampsia with healthy pregnancy to establish whether there is increased lipolysis. Subcutaneous and visceral adipose tissue biopsies were collected at caesarean section from healthy (n=31) and preeclampsia (n=13) mothers. Lipolysis in response to isoproterenol (200 nmol/L) and insulin (10 nmol/L) was assessed. In healthy pregnancy, subcutaneous adipocytes had higher diameter than visceral adipocytes (Padipocyte mean diameter in preeclampsia was similar to that in healthy pregnant controls, but cell distribution was shifted toward smaller cell diameter in preeclampsia. Total lipolysis rates under all conditions were lower in healthy visceral than subcutaneous adipocytes but did not differ after normalization for cell diameter. Visceral adipocyte insulin sensitivity was lower than subcutaneous in healthy pregnancy and inversely correlated with plasma triglyceride (r=-0.50; P=0.004). Visceral adipose tissue had lower ADRB3, LPL, and leptin and higher insulin receptor messenger RNA expression than subcutaneous adipose tissue. There was no difference in subcutaneous adipocyte lipolysis rates between preeclampsia and healthy controls, but subcutaneous adipocytes had lower sensitivity to insulin in preeclampsia, independent of cell diameter (Pinsulin suppression of subcutaneous adipocyte lipolysis may increase the burden of plasma fatty acids that the mother has to process in preeclampsia.

  3. Aerobic exercise training improves atrial natriuretic peptide and catecholamine-mediated lipolysis in obese women with polycystic ovary syndrome.

    Science.gov (United States)

    Moro, Cedric; Pasarica, Magdalena; Elkind-Hirsch, Karen; Redman, Leanne M

    2009-07-01

    The aim was to investigate the impact of polycystic ovary syndrome (PCOS) on the regulation of lipolysis by catecholamine and for the first time atrial natriuretic peptide (ANP) before and after 16 wk of aerobic training. Eight hyperandrogenic obese women with PCOS [age, 25 +/- 1 yr; body mass index (BMI), 32.0 +/- 1.6 kg/m(2)] and seven healthy BMI-matched controls participated. Studies were performed before and after a 16-wk exercise training program in women with PCOS and cross-sectionally in a group of BMI-matched controls. Lipolysis was measured in vitro in isolated adipocytes and in vivo by microdialysis of sc abdominal adipose tissue before and during a hyperinsulinemic euglycemic clamp. In vitro, baseline and maximal ANP- and isoproterenol-induced lipolysis was markedly reduced in PCOS women. Baseline (P lipolysis, however, was remarkably increased after training, independent of changes in body weight and sex hormones. These functional improvements were supported by an increased 1) lipolytic sensitivity for ANP (1.3-fold; P lipolysis during the hyperinsulinemic euglycemic clamp was also reduced in PCOS. Together, these data show that the regulation of lipolysis by the main endocrine hormones is impaired in women with PCOS. These lipolytic defects can be partly reversed by aerobic exercise training independent of changes in body fat mass and sex hormones.

  4. Exploring the fate of liposomes in the intestine by dynamic in vitro lipolysis

    DEFF Research Database (Denmark)

    Parmentier, Johannes; Thomas, Nicky; Müllertz, Anette

    2012-01-01

    , a dynamic in vitro lipolysis model, which so far has only been used for the in vitro characterisation of other lipid-based drug delivery systems, was applied to different liposomal formulations. Liposome size and phospholipid (PL) digestion were determined as two markers for liposome stability. In addition......Liposomes are generally well tolerated drug delivery systems with a potential use for the oral route. However, little is known about the fate of liposomes during exposure to the conditions in the gastro-intestinal tract (GIT). To gain a better understanding of liposome stability in the intestine...... of aggregates of around 1µm in diameter was observed over time. After 60min lipolysis more than 80% of PLs of the SPC-liposomes were digested, but dependent on the liposome concentration only a slight change in size and size distribution could be observed. Although EPC-3 formulations did form aggregates during...

  5. Adipose tissue mitochondrial respiration and lipolysis before and after a weight loss by diet and RYGB

    DEFF Research Database (Denmark)

    Hansen, Merethe; Lund, Michael T.; Gregers, Emilie

    2015-01-01

    OBJECTIVE: To study adipose tissue mitochondrial respiration and lipolysis following a massive weight loss. METHODS: High resolution respirometry of adipose tissue biopsies and tracer determined whole body lipolysis. Sixteen obese patients with type 2 diabetes (T2DM) and 27 without (OB) were...... fat mass was always higher relative to the body fat mass (%) compared to OB. CONCLUSIONS: Adipose tissue mitochondrial respiratory capacity increases with RYGB. Adipocytes adapt to massive weight......, no differences in oxidative capacity after RYGB were seen. The ratio between the oxidative phosphorylation system capacity (P) and the capacity of the electron transfer system (E) increased 18 months after RYGB in both groups (P fat mass was similar in the two groups and was increased (P...

  6. Penetration enhancement in mouse skin and lipolysis in adipocytes by TAT-GKH, a new cosmetic ingredient.

    Science.gov (United States)

    Lim, Jun Man; Chang, Min Youl; Park, Sun Gyoo; Kang, Nae Gyu; Song, Young Sook; Lee, Young Hwa; Yoo, Young Chang; Cho, Wan Goo; Choi, Soo Young; Kang, She Hoon

    2003-01-01

    Since the basic domain of human immunodeficiency virus type I (HIV-1) transactivator of transcription (TAT) protein was reported to possess the ability to traverse biological membranes efficiently, various therapeutic proteins have been attached to TAT for the purpose of therapy. In this study, the tripeptide GKH (glycine-lysine-histidine) derived from parathyroid hormone (PTH), known as lipolytic peptide, was attached to 9-poly lysine (TAT) to be used as a cosmetic ingredient in slimming products. TAT-GKH at 10(-5) M induced approximately 37.6% and 41.5% maximal lipolytic effects in cultured 3T3-L1 differentiated adipocytes and in epididymal adipocytes isolated from rats, respectively, compared with basal lipolysis. The lipolytic effect of GKH was not changed by TAT-GKH fusion. In cytotoxicity tests, there was no cytotoxicity in any dose concentration of TAT-GKH. We confirmed that TAT-GKH induced lipolytic activity by GKH without cytotoxicity and with the possibility of its use as a safe cosmetic ingredient. TAT-GKH elevated penetration into excised hairless mice skin 36 times more efficiently than GKH. TAT-GKH can be used as a cosmetic ingredient in slimming products, with both penetration enhancement and lipolytic effect without cytotoxicity.

  7. Impact of gastrointestinal lipolysis on oral lipid-based formulations and bioavailability of lipophilic drugs.

    Science.gov (United States)

    Carrière, Frédéric

    2016-06-01

    Oil-in-water emulsions are common vehicles for lipids as nutrients and for the delivery of poorly water-soluble drugs. Enhancing oral bioavailability of these drugs using lipid-based formulations (LBF) or self-emulsifying drug delivery systems is one of the current challenges in pharmaceutical industry. Many of the compounds found in LBF (acylglycerols, surfactants with esterified fatty acids, …) are however potential substrates for digestive enzymes. Their digestion (or lipolysis) in the gastrointestinal (GI) tract is critical for drug dissolution and absorption: it can be beneficial (drug solubilization/dispersion) or deleterous (drug precipitation) depending on the drug-LBF association. A better understanding of the fate of LBF in the GI tract is therefore required to engineer efficient lipid-based drug delivery systems. In vitro models for testing simultaneously LBF digestion and drug dispersion are in development to predict drug solubilization and bioavailability, select the best drug-LBF association and obtain better in vitro-in vivo correlations. So far, research in this area has focused on LBF lipolysis under intestinal conditions because the small intestine is the main target for drug delivery and absorption, as well as the main site of digestion by pancreatic enzymes. Lipolysis however starts within the stomach through the action of gastric lipase, the first enzyme involved in fat digestion in humans. In vitro digestion experiments show that most LBFs are submitted to gastric lipolysis, and therefore, both intragastric and intestinal digestions are critical for the fate of LBF and drug solubility.

  8. Role of cannabinoid receptor 1 in human adipose tissue for lipolysis regulation and insulin resistance.

    Science.gov (United States)

    Sidibeh, Cherno O; Pereira, Maria J; Lau Börjesson, Joey; Kamble, Prasad G; Skrtic, Stanko; Katsogiannos, Petros; Sundbom, Magnus; Svensson, Maria K; Eriksson, Jan W

    2017-03-01

    We recently showed that the peripheral cannabinoid receptor type 1 (CNR1) gene is upregulated by the synthetic glucocorticoid dexamethasone. CNR1 is highly expressed in the central nervous system and has been a drug target for the treatment of obesity. Here we explore the role of peripheral CNR1 in states of insulin resistance in human adipose tissue. Subcutaneous adipose tissue was obtained from well-controlled type 2 diabetes subjects and controls. Subcutaneous adipose tissue gene expression levels of CNR1 and endocannabinoid synthesizing and degrading enzymes were assessed. Furthermore, paired human subcutaneous adipose tissue and omental adipose tissue from non-diabetic volunteers undergoing kidney donation or bariatric surgery, was incubated with or without dexamethasone. Subcutaneous adipose tissue obtained from volunteers through needle biopsy was incubated with or without dexamethasone and in the presence or absence of the CNR1-specific antagonist AM281. CNR1 gene and protein expression, lipolysis and glucose uptake were evaluated. Subcutaneous adipose tissue CNR1 gene expression levels were 2-fold elevated in type 2 diabetes subjects compared with control subjects. Additionally, gene expression levels of CNR1 and endocannabinoid-regulating enzymes from both groups correlated with markers of insulin resistance. Dexamethasone increased CNR1 expression dose-dependently in subcutaneous adipose tissue and omental adipose tissue by up to 25-fold. Dexamethasone pre-treatment of subcutaneous adipose tissue increased lipolysis rate and reduced glucose uptake. Co-incubation with the CNR1 antagonist AM281 prevented the stimulatory effect on lipolysis, but had no effect on glucose uptake. CNR1 is upregulated in states of type 2 diabetes and insulin resistance. Furthermore, CNR1 is involved in glucocorticoid-regulated lipolysis. Peripheral CNR1 could be an interesting drug target in type 2 diabetes and dyslipidemia.

  9. Slowing down fat digestion and absorption by an oxadiazolone inhibitor targeting selectively gastric lipolysis.

    Science.gov (United States)

    Point, Vanessa; Bénarouche, Anais; Zarrillo, Julie; Guy, Alexandre; Magnez, Romain; Fonseca, Laurence; Raux, Brigitt; Leclaire, Julien; Buono, Gérard; Fotiadu, Frédéric; Durand, Thierry; Carrière, Frédéric; Vaysse, Carole; Couëdelo, Leslie; Cavalier, Jean-François

    2016-11-10

    Based on a previous study and in silico molecular docking experiments, we have designed and synthesized a new series of ten 5-Alkoxy-N-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one derivatives (RmPPOX). These molecules were further evaluated as selective and potent inhibitors of mammalian digestive lipases: purified dog gastric lipase (DGL) and guinea pig pancreatic lipase related protein 2 (GPLRP2), as well as porcine (PPL) and human (HPL) pancreatic lipases contained in porcine pancreatic extracts (PPE) and human pancreatic juices (HPJ), respectively. These compounds were found to strongly discriminate classical pancreatic lipases (poorly inhibited) from gastric lipase (fully inhibited). Among them, the 5-(2-(Benzyloxy)ethoxy)-3-(3-PhenoxyPhenyl)-1,3,4-Oxadiazol-2(3H)-one (BemPPOX) was identified as the most potent inhibitor of DGL, even more active than the FDA-approved drug Orlistat. BemPPOX and Orlistat were further compared in vitro in the course of test meal digestion, and in vivo with a mesenteric lymph duct cannulated rat model to evaluate their respective impacts on fat absorption. While Orlistat inhibited both gastric and duodenal lipolysis and drastically reduced fat absorption in rats, BemPPOX showed a specific action on gastric lipolysis that slowed down the overall lipolysis process and led to a subsequent reduction of around 55% of the intestinal absorption of fatty acids compared to controls. All these data promote BemPPOX as a potent candidate to efficiently regulate the gastrointestinal lipolysis, and to investigate its link with satiety mechanisms and therefore develop new strategies to "fight against obesity". Copyright © 2016 Elsevier Masson SAS. All rights reserved.

  10. Influence of lipolysis and ketogenesis to metabolic and hematological parameters in dairy cows during periparturient period

    OpenAIRE

    Cincović R.M.; Belić Branislava; Radojičić Biljana; Hristov S.; Đoković R.

    2012-01-01

    The aim of this study was to examine the characteristics of the metabolic profile and complete blood count in cows in the periparturient period on the basis of the intensity of lipolysis and ketogenesis (concentration of non esterified fatty acid - NEFA and betahydroxybutyrate - BHB). Based on median values of NEFA and BHB cows were divided into 3 groups: cows physiologically burdened with catabolism (NEFA and BHB levels above the median one week after part...

  11. The Role of PDE3B Phosphorylation in the Inhibition of Lipolysis by Insulin

    OpenAIRE

    DiPilato, Lisa M.; Ahmad, Faiyaz; Harms, Matthew; Seale, Patrick; Manganiello, Vincent; Birnbaum, Morris J.

    2015-01-01

    Inhibition of adipocyte lipolysis by insulin is important for whole-body energy homeostasis; its disruption has been implicated as contributing to the development of insulin resistance and type 2 diabetes mellitus. The main target of the antilipolytic action of insulin is believed to be phosphodiesterase 3B (PDE3B), whose phosphorylation by Akt leads to accelerated degradation of the prolipolytic second messenger cyclic AMP (cAMP). To test this hypothesis genetically, brown adipocytes lacking...

  12. Early B-cell Factor 1 Regulates Adipocyte Morphology and Lipolysis in White Adipose Tissue

    OpenAIRE

    Gao, Hui; Mejhert, Niklas; Fretz, Jackie A.; Arner, Erik; Lorente-Cebrián, Silvia; Ehrlund, Anna; Dahlman-Wright, Karin; Gong, Xiaowei; Strömblad, Staffan; Douagi, Iyadh; Laurencikiene, Jurga; Dahlman, Ingrid; Daub, Carsten O.; Rydén, Mikael; Mark C Horowitz

    2014-01-01

    White adipose tissue (WAT) morphology characterized by hypertrophy (i.e. fewer but larger adipocytes) associates with increased adipose inflammation, lipolysis, insulin resistance and risk of diabetes. However, the causal relationships and the mechanisms controlling WAT morphology are unclear. Herein, we identified EBF1 as an adipocyte-expressed transcription factor with decreased expression/activity in WAT hypertrophy. In human adipocytes, the regulatory targets of EBF1 were enriched for gen...

  13. Mesenteric Fat Lipolysis Mediates Obesity-associated Hepatic Steatosis and Insulin Resistance

    OpenAIRE

    Wueest, Stephan; Item, Flurin; Lucchini, Fabrizio C; Challa, Tenagne D; Muller, Werner; Blüher, Matthias; Konrad, Daniel

    2016-01-01

    Hepatic steatosis and insulin resistance are among the most prevalent metabolic disorders and are tightly associated with obesity and type 2 diabetes. However, the underlying mechanisms linking obesity to hepatic lipid accumulation and insulin resistance are incompletely understood. Glycoprotein 130 (gp130) is the common signal transducer of all interleukin 6 (IL-6) cytokines. We provide evidence that gp130-mediated adipose tissue lipolysis promotes hepatic steatosis and insulin resistance. I...

  14. Activation of alpha(2)-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects.

    Science.gov (United States)

    Stich, V; De Glisezinski, I; Crampes, F; Hejnova, J; Cottet-Emard, J M; Galitzky, J; Lafontan, M; Rivière, D; Berlan, M

    2000-08-01

    With the use of the microdialysis method, exercise-induced lipolysis was investigated in subcutaneous adipose tissue (SCAT) in obese subjects and compared with lean ones, and the effect of blockade of alpha(2)-adrenergic receptors (ARs) on lipolysis during exercise was explored. Changes in extracellular glycerol concentrations and blood flow were measured in SCAT in a control microdialysis probe at rest and during 60-min exercise bouts (50% of heart rate reserve) and in a probe supplemented with the alpha(2)-AR antagonist phentolamine. At rest and during exercise, plasma norepinephrine and epinephrine concentrations were not different in obese compared with lean men. In the basal state, plasma and extracellular glycerol concentrations were higher, whereas blood flow was lower in SCAT of obese subjects. During exercise, the increase of plasma glycerol was higher in obese subjects (115 +/- 35 vs. 65 +/- 21 micromol/l). Oppositely, the exercise-induced increase in extracellular glycerol concentrations in SCAT was five- to sixfold lower in obese than in lean subjects (50 +/- 14 vs. 318 +/- 53 micromol/l). The exercise-induced increase in extracellular glycerol concentration was not significantly modified by phentolamine infusion in lean subjects but was strongly enhanced in the obese subjects and reached the concentrations found in lean sujects (297 +/- 46 micromol/l). These findings demonstrate that the physiological stimulation of SCAT adipocyte alpha(2)-ARs during exercice-induced sympathetic nervous system activation contributes to the blunted lipolysis noted in obese men.

  15. Effect of dietary docosahexaenoic acid on lipogenesis and lipolysis in black sea bream, Acanthopagrus schlegeli

    Institute of Scientific and Technical Information of China (English)

    JI Hong; OM Ahamd Daud; YOSHIMATSU Takao; UMINO Testuya; NAKAGAWA Heisuke; FURUHASHI Makoto; SAKAMOTO Shuichi

    2007-01-01

    Hatchery-reared juvenile black sea breams are characterized by a low level of highly unsaturated fatty acids in their bodies, as compared with wild fish. To assess the effect of docosahaxaenoic acid (DHA) on lipogenic and lipolysis enzymes, one-year fish were reared on a casein-based purified diet and a DHA fortified diet (1.5% DHA ethyl ester/kg diet) for 60 d, followed with a period of 55 d for starvation. Dietary DHA was effectively incorporated into the fish body. Fortification of DHA depressed activities of glucose-6-phosphate dehydrogenase and NADP-isocitrate dehydrogenase as lipogenic enzymes in the hepatopancreas and intraperitoneal fat body. Carnitine palmitoyltransferase as lipolysis enzyme in the hepatopancreas was active in the DHA fortified fish. Starvation after feeding experiment induced increased carnitine palmitoyltransferase activity in both control and DHA fortified fish and the activity remained higher in the DHA fortified fish, while the monoenes were selectively consumed prior to highly unsaturated fatty acids. These results indicated that dietary DHA depressed lipogenesis and activated lipolysis.

  16. Impact of various emulsifiers on ALA bioavailability and chylomicron synthesis through changes in gastrointestinal lipolysis.

    Science.gov (United States)

    Couëdelo, L; Amara, S; Lecomte, M; Meugnier, E; Monteil, J; Fonseca, L; Pineau, G; Cansell, M; Carrière, F; Michalski, M C; Vaysse, C

    2015-05-01

    Formulating healthy food rich in omega 3 fatty acids requires prior knowledge of the parameters influencing their bioavailability and their metabolic fate. In this context, we studied the effects of various emulsifiers widely used in the food industry, on the gastrointestinal lipolysis of flaxseed oil emulsions in an in vitro model and on the intestinal absorption and lymphatic secretion of alpha-linolenic acid (ALA) in rats. In vitro data showed that the emulsification of flaxseed oil with soya lecithin improved the gastric lipolysis of the oil (+30%), while the presence of Tween 80 or of sodium caseinate decreased it (-80% and -40%, respectively). The in vivo data demonstrated that the intestinal absorption and the lymphatic secretion of ALA were improved with soya lecithin (Cmax = 24 mg mL(-1)) and reduced in the presence of sodium caseinate (Cmax = 7 mg mL(-1)) compared to unemulsified flaxseed oil (Cmax = 16 mg mL(-1)); Tween 80 had no effect. In addition, the synthesized chylomicrons were notably larger and more numerous with soya lecithin whereas they were smaller in the presence of sodium caseinate (p lecithin via an improved lipolysis, favouring the intestinal absorption of ALA and the secretion of many large chylomicrons in lymph.

  17. Micro RNA-124a Regulates Lipolysis via Adipose Triglyceride Lipase and Comparative Gene Identification 58

    Directory of Open Access Journals (Sweden)

    Suman K. Das

    2015-04-01

    Full Text Available Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG. Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2 and its co-activator comparative gene identification 58 (CGI-58/ABHD5. Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3'UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration.

  18. Lipolysis and lipid oxidation during processing of Chinese traditional smoke-cured bacon.

    Science.gov (United States)

    Huang, Yechuan; Li, Hongjun; Huang, Tian; Li, Feng; Sun, Juan

    2014-04-15

    Lipolysis and lipid oxidation as well as the relationship between them during processing of Chinese traditional smoke-cured bacon were studied by evaluating the changes in physicochemical parameters, lipase and lipoxygenase (LOX) activities, lipid content, fatty acid composition, peroxide value (POV), and thiobarbituric acid reactive substances (TBARS). Besides phospholipids, triacylglycerols (TAG) were an important source of free fatty acids in bacon, resulting in an increase in free fatty acid content in the mid-late stage of processing, whilst phospholipids hydrolysed intensely in the early stage. Preferential lipolysis was observed for polyunsaturated fatty acids in phospholipids and for linoleic and palmitic acids in TAG. The lipolysis of TAG and phospholipids was independent and catalysed by acid lipase and phospholipase, respectively. ANOVA-partial least squares regression (APLSR) analysis showed that POV and TBARS were poorly related to LOX and closely associated with phospholipid degradation. Therefore, autoxidation may be the main cause of muscle lipid oxidation in smoke-cured bacon, which was promoted by phospholipid hydrolysis.

  19. Food-grade micro-encapsulation systems that may induce satiety via delayed lipolysis: A review.

    Science.gov (United States)

    Corstens, Meinou N; Berton-Carabin, Claire C; de Vries, Renko; Troost, Freddy J; Masclee, Ad A M; Schroën, Karin

    2017-07-03

    The increasing prevalence of overweight and obesity requires new, effective prevention and treatment strategies. One approach to reduce energy intake is by developing novel foods with increased satiating properties, which may be accomplished by slowing down lipolysis to deliver substrates to the ileum, thereby enhancing natural gut-brain signaling pathways of satiety that are normally induced by meal intake. To develop slow release food additives, their processing in the gastrointestinal tract has to be understood; therefore, we start from a general description of the digestive system and relate that to in vitro modeling, satiety, and lipolytic mechanisms. The effects of physicochemical lipid composition, encapsulation matrix, and interfacial structure on lipolysis are emphasized. We give an overview of techniques and materials used, and discuss partitioning, which may be a key factor for encapsulation performance. Targeted release capsules that delay lipolysis form a real challenge because of the high efficiency of the digestive system; hardly any proof was found that intact orally ingested lipids can be released in the ileum and thereby induce satiety. We expect that this challenge could be tackled with structured o/w-emulsion-based systems that have some protection against lipase, e.g., by hindering bile salt adsorption and/or delaying lipase diffusion.

  20. Mesenteric Fat Lipolysis Mediates Obesity-Associated Hepatic Steatosis and Insulin Resistance.

    Science.gov (United States)

    Wueest, Stephan; Item, Flurin; Lucchini, Fabrizio C; Challa, Tenagne D; Müller, Werner; Blüher, Matthias; Konrad, Daniel

    2016-01-01

    Hepatic steatosis and insulin resistance are among the most prevalent metabolic disorders and are tightly associated with obesity and type 2 diabetes. However, the underlying mechanisms linking obesity to hepatic lipid accumulation and insulin resistance are incompletely understood. Glycoprotein 130 (gp130) is the common signal transducer of all interleukin 6 (IL-6) cytokines. We provide evidence that gp130-mediated adipose tissue lipolysis promotes hepatic steatosis and insulin resistance. In obese mice, adipocyte-specific gp130 deletion reduced basal lipolysis and enhanced insulin's ability to suppress lipolysis from mesenteric but not epididymal adipocytes. Consistently, free fatty acid levels were reduced in portal but not in systemic circulation of obese knockout mice. Of note, adipocyte-specific gp130 knockout mice were protected from high-fat diet-induced hepatic steatosis as well as from insulin resistance. In humans, omental but not subcutaneous IL-6 mRNA expression correlated positively with liver lipid accumulation (r = 0.31, P insulin resistance and steatosis. Therefore, blocking IL-6 cytokine signaling in (mesenteric) adipocytes may be a novel approach to blunting detrimental fat-liver crosstalk in obesity. © 2016 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  1. Effects of cortisol on lipolysis and regional interstitial glycerol levels in humans.

    Science.gov (United States)

    Djurhuus, C B; Gravholt, C H; Nielsen, S; Mengel, A; Christiansen, J S; Schmitz, O E; Møller, N

    2002-07-01

    Cortisol's effects on lipid metabolism are controversial and may involve stimulation of both lipolysis and lipogenesis. This study was undertaken to define the role of physiological hypercortisolemia on systemic and regional lipolysis in humans. We investigated seven healthy young male volunteers after an overnight fast on two occasions by means of microdialysis and palmitate turnover in a placebo-controlled manner with a pancreatic pituitary clamp involving inhibition with somatostatin and substitution of growth hormone, glucagon, and insulin at basal levels. Hydrocortisone infusion increased circulating concentrations of cortisol (888 +/- 12 vs. 245 +/- 7 nmol/l). Interstitial glycerol concentrations rose in parallel in abdominal (327 +/- 35 vs. 156 +/- 30 micromol/l; P = 0.05) and femoral (178 +/- 28 vs. 91 +/- 22 micromol/l; P = 0.02) adipose tissue. Systemic [(3)H]palmitate turnover increased (165 +/- 17 vs. 92 +/- 24 micromol/min; P = 0.01). Levels of insulin, glucagon, and growth hormone were comparable. In conclusion, the present study unmistakably shows that cortisol in physiological concentrations is a potent stimulus of lipolysis and that this effect prevails equally in both femoral and abdominal adipose tissue.

  2. In vitro lipolysis tests on lipid nanoparticles: comparison between lipase/co-lipase and pancreatic extract.

    Science.gov (United States)

    Jannin, Vincent; Dellera, Eleonora; Chevrier, Stéphanie; Chavant, Yann; Voutsinas, Christophe; Bonferoni, Cristina; Demarne, Frédéric

    2015-01-01

    Solid lipid nanoparticles (SLNs) and nanostructured lipid carriers (NLC) are lipid nanocarriers aimed to the delivery of drugs characterized by a low bioavailability, such as poorly water-soluble drugs and peptides or proteins. The oral administration of these lipid nanocarriers implies the study of their lipolysis in presence of enzymes that are commonly involved in dietary lipid digestion in the gastrointestinal tract. In this study, a comparison between two methods was performed: on one hand, the lipase/co-lipase assay, commonly described in the literature to study the digestion of lipid nanocarriers, and on the other hand, the lipolysis test using porcine pancreatic extract and the pH-stat apparatus. This pancreatic extract contains both the pancreatic lipase and carboxyl ester hydrolase (CEH) that permit to mimic in a biorelevant manner the duodenal digestive lipolysis. The test was performed by means of a pH-stat apparatus to work at constant pH, 5.5 or 6.25, representing respectively the fasted or fed state pH conditions. The evolution of all acylglycerol entities was monitored during the digestion by sampling the reaction vessel at different time points, until 60 min, and the lipid composition of the digest was analyzed by gas chromatography. SLN and NLC systems obtained with long-chain saturated acylglycerols were rapidly and completely digested by pancreatic enzymes. The pH-stat titration method appears to be a powerful technique to follow the digestibility of these solid lipid-based nanoparticles.

  3. AHNAK deficiency promotes browning and lipolysis in mice via increased responsiveness to β-adrenergic signalling.

    Science.gov (United States)

    Shin, Jae Hoon; Lee, Seo Hyun; Kim, Yo Na; Kim, Il Yong; Kim, Youn Ju; Kyeong, Dong Soo; Lim, Hee Jung; Cho, Soo Young; Choi, Junhee; Wi, Young Jin; Choi, Jae-Hoon; Yoon, Yeo Sung; Bae, Yun Soo; Seong, Je Kyung

    2016-03-18

    In adipose tissue, agonists of the β3-adrenergic receptor (ADRB3) regulate lipolysis, lipid oxidation, and thermogenesis. The deficiency in the thermogenesis induced by neuroblast differentiation-associated protein AHNAK in white adipose tissue (WAT) of mice fed a high-fat diet suggests that AHNAK may stimulate energy expenditure via development of beige fat. Here, we report that AHNAK deficiency promoted browning and thermogenic gene expression in WAT but not in brown adipose tissue of mice stimulated with the ADRB3 agonist CL-316243. Consistent with the increased thermogenesis, Ahnak(-/-) mice exhibited an increase in energy expenditure, accompanied by elevated mitochondrial biogenesis in WAT depots in response to CL-316243. Additionally, AHNAK-deficient WAT contained more eosinophils and higher levels of type 2 cytokines (IL-4/IL-13) to promote browning of WAT in response to CL-316243. This was associated with enhanced sympathetic tone in the WAT via upregulation of adrb3 and tyrosine hydroxylase (TH) in response to β-adrenergic activation. CL-316243 activated PKA signalling and enhanced lipolysis, as evidenced by increased phosphorylation of hormone-sensitive lipase and release of free glycerol in Ahnak(-/-) mice compared to wild-type mice. Overall, these findings suggest an important role of AHNAK in the regulation of thermogenesis and lipolysis in WAT via β-adrenergic signalling.

  4. Micro RNA-124a regulates lipolysis via adipose triglyceride lipase and comparative gene identification 58.

    Science.gov (United States)

    Das, Suman K; Stadelmeyer, Elke; Schauer, Silvia; Schwarz, Anna; Strohmaier, Heimo; Claudel, Thiery; Zechner, Rudolf; Hoefler, Gerald; Vesely, Paul W

    2015-04-16

    Lipolysis is the biochemical pathway responsible for the catabolism of cellular triacylglycerol (TG). Lipolytic TG breakdown is a central metabolic process leading to the generation of free fatty acids (FA) and glycerol, thereby regulating lipid, as well as energy homeostasis. The precise tuning of lipolysis is imperative to prevent lipotoxicity, obesity, diabetes and other related metabolic disorders. Here, we present our finding that miR-124a attenuates RNA and protein expression of the major TG hydrolase, adipose triglyceride lipase (ATGL/PNPLA2) and its co-activator comparative gene identification 58 (CGI-58/ABHD5). Ectopic expression of miR-124a in adipocytes leads to reduced lipolysis and increased cellular TG accumulation. This phenotype, however, can be rescued by overexpression of truncated Atgl lacking its 3'UTR, which harbors the identified miR-124a target site. In addition, we observe a strong negative correlation between miR-124a and Atgl expression in various murine tissues. Moreover, miR-124a regulates the expression of Atgl and Cgi-58 in murine white adipose tissue during fasting as well as the expression of Atgl in murine liver, during fasting and re-feeding. Together, these results point to an instrumental role of miR-124a in the regulation of TG catabolism. Therefore, we suggest that miR-124a may be involved in the regulation of several cellular and organismal metabolic parameters, including lipid storage and plasma FA concentration.

  5. Pioglitazone improves insulin sensitivity, reduces visceral fat and stimulates lipolysis in non diabetic dialyzed patients

    Directory of Open Access Journals (Sweden)

    Anne Zanchi

    2012-06-01

    Full Text Available Insulin resistance is common in dialyzed patients and is associated with increased mortality and protein-energy wasting. The aim of this study was to investigate the effect of pioglitazone (PIO, a powerful insulin sensitizer, on insulin sensitivity, body composition and adipose tissue metabolism, in dialyzed patients. A double blind randomized cross-over study was performed in non diabetic dialysis patients. Each patient followed 2 treatment phases of 16 weeks, starting either with oral PIO 45 mg/d or placebo (PL, and then switched to the other phase. At the end of each phase, patients underwent hyperinsulinemic euglycemic clamps, dual energy X-ray absorptiometry, an abdominal CT, and extensive plasma biochemical analysis. Twelve patients including 8 HD (59.6±4.4 y and 4 PD patients (43.5±3.6 y were recruited. Nine patients completed both phases and 3 patients dropped out (renal transplantation/2 HD and peritonitis/1 PD. PIO was safe and well tolerated. Under PIO, insulin sensitivity improved, as assessed by increased total glucose disposal rate (1.98±0.24 for PIO versus 1.58±0.12 umol/kg/min for PL, p<0.05, and reduced glucose endogenous hepatic production. PIO did not affect post-dialysis body weight, total fat and lean body mass, but significantly reduced visceral adipose tissue (VAT area and the VAT/SAT (subcutaneous adipose tissue ratio. HDL-cholesterol significantly increased. PIO decreased CRP (3.96±1.44 mg/l vs 7.88±2.56, p<0.05, plasma leptin, and dramatically reduced leptin/adiponectin ratio. Glycerol turnover, circulating glycerol and non esterified fatty acids were paradoxically increased. In conclusion, the improvement in insulin sensitivity by PIO, in non diabetic dialyzed patients, was associated with favorable metabolic effects, reduction in inflammation and body fat redistribution. The stimulation of systemic lipolysis was a surprising finding which may reflect adipose tissue remodeling and/or a paradoxical lypolitic

  6. Berardinelli-seip congenital lipodystrophy 2/seipin is a cell-autonomous regulator of lipolysis essential for adipocyte differentiation.

    Science.gov (United States)

    Chen, Weiqin; Chang, Benny; Saha, Pradip; Hartig, Sean M; Li, Lan; Reddy, Vasumathi Theegala; Yang, Yisheng; Yechoor, Vijay; Mancini, Michael A; Chan, Lawrence

    2012-03-01

    Mutations in BSCL2 underlie human congenital generalized lipodystrophy. We inactivated Bscl2 in mice to examine the mechanisms whereby absence of Bscl2 leads to adipose tissue loss and metabolic disorders. Bscl2(-/-) mice develop severe lipodystrophy of white adipose tissue (WAT), dyslipidemia, insulin resistance, and hepatic steatosis. In vitro differentiation of both Bscl2(-/-) murine embryonic fibroblasts (MEFs) and stromal vascular cells (SVCs) reveals normal early-phase adipocyte differentiation but a striking failure in terminal differentiation due to unbridled cyclic AMP (cAMP)-dependent protein kinase A (PKA)-activated lipolysis, which leads to loss of lipid droplets and silencing of the expression of adipose tissue-specific transcription factors. Importantly, such defects in differentiation can be largely rescued by inhibitors of lipolysis but not by a gamma peroxisome proliferator-activated receptor (PPARγ) agonist. The residual epididymal WAT (EWAT) in Bscl2(-/-) mice displays enhanced lipolysis. It also assumes a "brown-like" phenotype with marked upregulation of UCP1 and other brown adipose tissue-specific markers. Together with decreased Pref1 but increased C/EBPβ levels, these changes highlight a possible increase in cAMP signaling that impairs terminal adipocyte differentiation in the EWAT of Bscl2(-/-) mice. Our study underscores the fundamental role of regulated cAMP/PKA-mediated lipolysis in adipose differentiation and identifies Bscl2 as a novel cell-autonomous determinant of activated lipolysis essential for terminal adipocyte differentiation.

  7. ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation.

    Science.gov (United States)

    Lindahl, Maria; Petrlova, Jitka; Dalla-Riva, Jonathan; Wasserstrom, Sebastian; Rippe, Catarina; Domingo-Espin, Joan; Kotowska, Dorota; Krupinska, Ewa; Berggreen, Christine; Jones, Helena A; Swärd, Karl; Lagerstedt, Jens O; Göransson, Olga; Stenkula, Karin G

    2015-12-01

    ApoA-I, the main protein component of HDL, is suggested to be involved in metabolic homeostasis. We examined the effects of Milano, a naturally occurring ApoA-I variant, about which little mechanistic information is available. Remarkably, high-fat-fed mice treated with Milano displayed a rapid weight loss greater than ApoA-I WT treated mice, and a significantly reduced adipose tissue mass, without an inflammatory response. Further, lipolysis in adipose cells isolated from mice treated with either WT or Milano was increased. In primary rat adipose cells, Milano stimulated cholesterol efflux and increased glycerol release, independently of β-adrenergic stimulation and phosphorylation of hormone sensitive lipase (Ser563) and perilipin (Ser522). Stimulation with Milano had a significantly greater effect on glycerol release compared with WT but similar effect on cholesterol efflux. Pharmacological inhibition or siRNA silencing of ABCA1 did not diminish Milano-stimulated lipolysis, although binding to the cell surface was decreased, as analyzed by fluorescence microscopy. Interestingly, methyl-β-cyclodextrin, a well-described cholesterol acceptor, dose-dependently stimulated lipolysis. Together, these results suggest that decreased fat mass and increased lipolysis following Milano treatment in vivo is partly explained by a novel mechanism at the adipose cell level comprising stimulation of lipolysis independently of the canonical cAMP/protein kinase A signaling pathway. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  8. Attenuated atrial natriuretic peptide-mediated lipolysis in subcutaneous adipocytes of obese type 2 diabetic men.

    Science.gov (United States)

    Verboven, Kenneth; Hansen, Dominique; Moro, Cedric; Eijnde, Bert O; Hoebers, Nicole; Knol, Joep; Bouckaert, Wim; Dams, Anne; Blaak, Ellen E; Jocken, Johan W E

    2016-07-01

    Catecholamines and atrial natriuretic peptide (ANP) are major regulators of adipocyte lipolysis. Although obesity is characterized by catecholamine resistance in subcutaneous adipose tissue (SCAT), data on ANP lipolytic response and sensitivity in different adipose tissue (AT) depots of metabolically distinct humans are scarce. Ex vivo catecholamine- and ANP-induced lipolysis was investigated in adipocytes derived from SCAT and visceral AT (VAT) depot of lean (n=13) and obese men, with (n=11) or without (n=18) type 2 diabetes (HbA1c lipolysis in SCAT was blunted in obese type 2 diabetics compared with age-matched lean men whereas non-diabetic obese subjects showed intermediate responses. This blunted ANP-mediated lipolytic response was accompanied by lower mRNA and protein expression of the type-A natriuretic peptide (NP) receptor and higher mRNA but reduced protein expression of the scavenging type-C receptor. Maximal ANP-induced lipolysis was lower in VAT compared with SCAT but not different between groups. Collectively, our data show that both ANP- and catecholamine-mediated lipolysis is attenuated in SCAT of obese men with type 2 diabetes, and might be partially explained by NP receptor defects. Therefore, improving maximal ANP responsiveness in adipose tissue might be a potential novel strategy to improve obesity-associated metabolic complications. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  9. Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle.

    Science.gov (United States)

    Alsted, Thomas J; Ploug, Thorkil; Prats, Clara; Serup, Annette K; Høeg, Louise; Schjerling, Peter; Holm, Cecilia; Zimmermann, Robert; Fledelius, Christian; Galbo, Henrik; Kiens, Bente

    2013-10-15

    In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P muscle, other TG lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.

  10. Proteomic Analysis of Plasma-Purified VLDL, LDL, and HDL Fractions from Atherosclerotic Patients Undergoing Carotid Endarterectomy: Identification of Serum Amyloid A as a Potential Marker

    Directory of Open Access Journals (Sweden)

    Antonio J. Lepedda

    2013-01-01

    Full Text Available Apolipoproteins are very heterogeneous protein family, implicated in plasma lipoprotein structural stabilization, lipid metabolism, inflammation, or immunity. Obtaining detailed information on apolipoprotein composition and structure may contribute to elucidating lipoprotein roles in atherogenesis and to developing new therapeutic strategies for the treatment of lipoprotein-associated disorders. This study aimed at developing a comprehensive method for characterizing the apolipoprotein component of plasma VLDL, LDL, and HDL fractions from patients undergoing carotid endarterectomy, by means of two-dimensional electrophoresis (2-DE coupled with Mass Spectrometry analysis, useful for identifying potential markers of plaque presence and vulnerability. The adopted method allowed obtaining reproducible 2-DE maps of exchangeable apolipoproteins from VLDL, LDL, and HDL. Twenty-three protein isoforms were identified by peptide mass fingerprinting analysis. Differential proteomic analysis allowed for identifying increased levels of acute-phase serum amyloid A protein (AP SAA in all lipoprotein fractions, especially in LDL from atherosclerotic patients. Results have been confirmed by western blotting analysis on each lipoprotein fraction using apo AI levels for data normalization. The higher levels of AP SAA found in patients suggest a role of LDL as AP SAA carrier into the subendothelial space of artery wall, where AP SAA accumulates and may exert noxious effects.

  11. Microdialysis assessment of local adipose tissue lipolysis during beta-adrenergic stimulation in upper-body-obese subjects with type II diabetes

    NARCIS (Netherlands)

    Blaak, E E; Kemerink, G J; Pakbiers, M T; Wolffenbuttel, B H; Heidendal, G A; Saris, W H

    1999-01-01

    The present study was designed to investigate indicators of abdominal adipose tissue lipolysis (microdialysis), and subcutaneous adipose tissue blood flow and whole-body lipolysis, in obesity-associated type II diabetes during overnight-fasted conditions (baseline) and during intravenous infusion of

  12. Regulation of Lipolysis and Adipose Tissue Signaling during Acute Endotoxin-Induced Inflammation: A Human Randomized Crossover Trial

    DEFF Research Database (Denmark)

    Rittig, Nikolaj; Bach, Ermina; Thomsen, Henrik Holm

    2016-01-01

    lipolysis in adipose tissue and is associated with increased pHSL and signs of increased PLIN1 phosphorylation combined with a trend toward decreased insulin signaling. The combination of these mechanisms appear to be the driving forces behind the increased lipolysis observed in the early stages of acute...... = 0.001) compared with Placebo. These effects were associated with increased phosphorylation of hormone sensitive lipase (pHSL) at ser650 in adipose tissue (p = 0.03), a trend towards elevated pHSL at ser552 (p = 0.09) and cAMP-dependent protein kinase A (PKA) phosphorylation of perilipin 1 (PLIN1) (p......BACKGROUND: Lipolysis is accelerated during the acute phase of inflammation, a process being regulated by pro-inflammatory cytokines (e.g. TNF-α), stress-hormones, and insulin. The intracellular mechanisms remain elusive and we therefore measured pro- and anti-lipolytic signaling pathways...

  13. Uninephrectomy in rats on a fixed food intake results in adipose tissue lipolysis implicating spleen cytokines.

    Directory of Open Access Journals (Sweden)

    Denis eArsenijevic

    2015-07-01

    Full Text Available The role of mild kidney dysfunction in altering lipid metabolism and promoting inflammation was investigated in uninephrectomized rats (UniNX compared to Sham-operated controls rats. The impact of UniNX was studied 1, 2 and 4 weeks after UniNX under mild food restriction at 90% of ad libitum intake to ensure the same caloric intake in both groups.UniNX resulted in the reduction of fat pad weight. UniNX was associated with increased circulating levels of beta-hydroxybutyrate and glycerol, as well as increased fat pad mRNA of hormone sensitive lipase and adipose triglyceride lipase, suggesting enhanced lipolysis. No decrease in fat pad lipogenesis as assessed by fatty acid synthase activity was observed.Circulating hormones known to regulate lipolysis such as leptin, T3, ghrelin, insulin, corticosterone, angiotensin 1 and angiotensin 2 were not different between the two groups. In contrast, a select group of circulating lipolytic cytokines, including interferon-gamma and granulocyte macrophage–colony stimulating factor, were increased after UniNX. These cytokines levels were elevated in the spleen, but decreased in the kidney, liver and fat pads. This could be explained by anti-inflammatory factors SIRT1, a member of the sirtuins, and the farnesoid x receptor, which were decreased in the spleen but elevated in the kidney, liver and fat pads (inguinal and epididymal. Our study suggests that UniNX induces adipose tissue lipolysis in response to increased levels of a subset of lipolytic cytokines of splenic origin.

  14. Cellulite: a new treatment approach combining subdermal Nd: YAG laser lipolysis and autologous fat transplantation.

    Science.gov (United States)

    Goldman, Alberto; Gotkin, Robert H; Sarnoff, Deborah S; Prati, Clarissa; Rossato, Flávia

    2008-01-01

    Cellulite is an alteration of the topography of the skin that occurs in body areas where fat deposition seems to be under the influence of estrogen: mainly the hips, buttocks, thighs, and abdomen. The presence of cellulite is a significant source of patient dissatisfaction. There is currently no cure or consistently effective treatment for cellulite. The authors sought to show that the subdermal application of the neodymium-doped yttrium aluminium garnet (Nd:YAG) laser combined with autologous fat transplantation is a safe and effective treatment for cellulite. From January 2003 to December 2006, 52 female patients with Curri grade III to IV cellulite were treated with subdermal 1064-nm Nd:YAG laser lipolysis combined with autologous fat transplantation. Patient assessment was collected for data analysis. After the treatment, tissue samples were obtained in some subjects in order to ascertain the histologic effects of the laser treatment. This treatment resulted in significant clinical improvement in cellulite. The adverse effects were mild and temporary, and the postoperative period was well tolerated. A majority of patients (84.6%) rated the results of treatment as either good or excellent. The treatment of severe cases of cellulite (Curri grades III and IV) by a combination of 1064-nm Nd:YAG laser lipolysis and autologous fat transplantation proved to be both safe and effective. In addition, subdermal laser lipolysis has the advantage of inducing neocollagenesis and stimulating postoperative skin tightening. This represents a new treatment option for the ubiquitous cellulite disorder. Although this treatment has shown promising results in this pilot study, further studies are necessary in order to draw final conclusions.

  15. Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans.

    Science.gov (United States)

    Djurhuus, C B; Gravholt, C H; Nielsen, S; Pedersen, S B; Møller, N; Schmitz, O

    2004-03-01

    Growth hormone (GH) and cortisol are important to ensure energy supplies during fasting and stress. In vitro experiments have raised the question whether GH and cortisol mutually potentiate lipolysis. In the present study, combined in vivo effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean males were examined four times over 510 min. Microdialysis catheters were inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of the thigh and abdomen. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of GH, insulin, and glucagon at baseline levels. At t = 150 min, administration was performed of NaCl (I), a 2 microg.kg(-1).min(-1) hydrocortisone infusion (II), a 200-microg bolus of GH (III), or a combination of II and III (IV). Systemic free fatty acid (FFA) turnover was estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose, insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II (0.50 +/- 0.08 microg/l, mean +/- SE). Peak levels during III and IV were approximately 9 microg/l. Cortisol levels rose to approximately 900 nmol/l in II and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased in response to both II and III. In IV, they were higher and equal to the isolated additive effects of the two hormones. In conclusion, we find that GH and cortisol stimulate systemic and regional lipolysis independently and in an additive manner when coadministered. On the basis of previous studies, we speculate that the mode of action is mediated though different pathways.

  16. TFE3 controls lipid metabolism in adipose tissue of male mice by suppressing lipolysis and thermogenesis.

    Science.gov (United States)

    Fujimoto, Yuri; Nakagawa, Yoshimi; Satoh, Aoi; Okuda, Kanako; Shingyouchi, Akiko; Naka, Ayano; Matsuzaka, Takashi; Iwasaki, Hitoshi; Kobayashi, Kazuto; Yahagi, Naoya; Shimada, Masako; Yatoh, Shigeru; Suzuki, Hiroaki; Yogosawa, Satomi; Izumi, Tetsuro; Sone, Hirohito; Urayama, Osamu; Yamada, Nobuhiro; Shimano, Hitoshi

    2013-10-01

    Transcription factor E3 (TFE3) is a transcription factor that binds to E-box motifs and promotes energy metabolism-related genes. We previously reported that TFE3 directly binds to the insulin receptor substrate-2 promoter in the liver, resulting in increased insulin response. However, the role of TFE3 in other tissues remains unclear. In this study, we generated adipose-specific TFE3 transgenic (aP2-TFE3 Tg) mice. These mice had a higher weight of white adipose tissue (WAT) and brown adipose tissue than wild-type (WT) mice under fasting conditions. Lipase activity in the WAT in these mice was lower than that in the WT mice. The mRNA level of adipose triglyceride lipase (ATGL), the rate-limiting enzyme for adipocyte lipolysis, was significantly decreased in aP2-TFE3 Tg mice. The expression of Foxo1, which directly activates ATGL expression, was also suppressed in transgenic mice. Promoter analysis confirmed that TFE3 suppressed promoter activities of the ATGL gene. In contrast, G0S2 and Perilipin1, which attenuate ATGL activity, were higher in transgenic mice than in WT mice. These results indicated that the decrease in lipase activity in adipose tissues was due to a decrease in ATGL expression and suppression of ATGL activity. We also showed that thermogenesis was suppressed in aP2-TFE3 Tg mice. The decrease in lipolysis in WAT of aP2-TFE3 Tg mice inhibited the supply of fatty acids to brown adipose tissue, resulting in the inhibition of the expression of thermogenesis-related genes such as UCP1. Our data provide new evidence that TFE3 regulates lipid metabolism by controlling the gene expression related to lipolysis and thermogenesis in adipose tissue.

  17. Vascular peptide endothelin-1 links fat accumulation with alterations of visceral adipocyte lipolysis.

    Science.gov (United States)

    van Harmelen, Vanessa; Eriksson, Anna; Aström, Gaby; Wåhlén, Kerstin; Näslund, Erik; Karpe, Fredrik; Frayn, Keith; Olsson, Tommy; Andersson, Jonas; Rydén, Mikel; Arner, Peter

    2008-02-01

    Visceral obesity increases risk of insulin resistance and type 2 diabetes. This may partly be due to a region-specific resistance to insulin's antilipolytic effect in visceral adipocytes. We investigated whether adipose tissue releases the vascular peptide endothelin-1 (ET-1) and whether ET-1 could account for regional differences in lipolysis. One group consisted of eleven obese and eleven nonobese subjects in whom ET-1 levels were compared between abdominal subcutaneous and arterialized blood samples. A second group included subjects undergoing anti-obesity surgery. Abdominal subcutaneous and visceral adipose tissues were obtained to study the effect of ET-1 on differentiated adipocytes regarding lipolysis and gene and protein expression. Adipose tissue had a marked net release of ET-1 in vivo, which was 2.5-fold increased in obesity. In adipocytes treated with ET-1, the antilipolytic effect of insulin was attenuated in visceral but not in subcutaneous adipocytes, which could not be explained by effects of ET-1 on adipocyte differentiation. ET-1 decreased the expression of insulin receptor, insulin receptor substrate-1 and phosphodiesterase-3B and increased the expression of endothelin receptor-B (ET(B)R) in visceral but not in subcutaneous adipocytes. These effects were mediated via ET(B)R with signals through protein kinase C and calmodulin pathways. The effect of ET-1 could be mimicked by knockdown of IRS-1. ET-1 is released from human adipose tissue and links fat accumulation to insulin resistance. It selectively counteracts insulin inhibition of visceral adipocyte lipolysis via ET(B)R signaling pathways, which affect multiple steps in insulin signaling.

  18. Differential effect of Se on insulin resistance: regulation of adipogenesis and lipolysis.

    Science.gov (United States)

    Wang, Xin; Wu, Hao; Long, Zi; Sun, Quangui; Liu, Jiangzheng; Liu, Ying; Hai, Chunxu

    2016-04-01

    Insulin resistance is the characteristic of type 2 diabetes mellitus and metabolic disorder. The biological effect of selenium (Se) on insulin sensitivity and metabolic function was contradictory. In this study, we designed two animal protocols to investigate the effect of physiological Se on high-fat (HF) diet-induced insulin resistance in mice and examined the influence of Se on adipocyte differentiation and lipolysis in isolated bone marrow stromal stem cells. The results showed that pre-treatment with Se, mimicking thiazolidinediones, increased adipocyte differentiation and fat deposit in adipose tissue and reduced ectopic lipid content and consequent ROS generation and mitochondrial dysfunction in livers, protecting against HF diet-induced insulin resistance. Post-treatment with Se promoted lipolysis in adipose tissue and ectopic lipid accumulation in livers and aggravated subsequent ROS generation and mitochondrial dysfunction, exacerbating insulin resistance induced by HF diet. Activation of GPx1 and Sepp1 was responsible for Se-exhibited bi-directional significance, which was at the crossroad of the biological effect of Se, leading to differential directions: one way is to accelerate mitotic clonal expansion and increase key regulators of adipocyte differentiation, such as PPARγ and C/EBPα/β, leading to enhancement of adipogenic differentiation; the other way is to activate PKA/HSL pathway, reinforcing lipolysis. Further studies are needed to elucidate the mechanism underlying GPx1 and Sepp1-exerted differential effects under different conditions. Anyhow, these findings may partly explain the contradiction of the biological significance of Se and demonstrate a novel understanding of the mechanism of Se-exerted benefit or harmful effects in the context of high consumption of fat.

  19. 18{beta}-Glycyrrhetinic acid inhibits adipogenic differentiation and stimulates lipolysis

    Energy Technology Data Exchange (ETDEWEB)

    Moon, Myung-Hee; Jeong, Jae-Kyo; Lee, You-Jin; Seol, Jae-Won; Ahn, Dong-Choon; Kim, In-Shik [Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of); Park, Sang-Youel, E-mail: sypark@chonbuk.ac.kr [Center for Healthcare Technology Development, Biosafety Research Institute, College of Veterinary Medicine, Chonbuk National University, Jeonju, Jeonbuk 561-756 (Korea, Republic of)

    2012-04-20

    Highlights: Black-Right-Pointing-Pointer 18{beta}-GA inhibits adipogenic differentiation in 3T3-L1 preadipocytes and stimulates lipolysis in differentiated adipocytes. Black-Right-Pointing-Pointer Anti-adipogenic effect of 18{beta}-GA is caused by down-regulation of PPAR{gamma} and inactivation of Akt signalling. Black-Right-Pointing-Pointer Lipolytic effect of 18{beta}-GA is mediated by up-regulation of HSL, ATGL and perilipin and activation of HSL. -- Abstract: 18{beta}-Glycyrrhetinic acid (18{beta}-GA) obtained from the herb liquorice has various pharmacological properties including anti-inflammatory and anti-bacterial activities. However, potential biological anti-obesity activities are unclear. In this study, novel biological activities of 18{beta}-GA in the adipogenesis of 3T3-L1 preadipocytes and in lipolysis of differentiated adipocytes were identified. Mouse 3T3-L1 cells were used as an in vitro model of adipogenesis and lipolysis, using a mixture of insulin/dexamethasone/3-isobutyl-1-methylxanthine (IBMX) to induce differentiation. The amount of lipid droplet accumulation was determined by an AdipoRed assay. The expression of several adipogenic transcription factors and enzymes was investigated using real-time reverse transcriptase-polymerase chain reaction (RT-PCR) and Western blotting. 18{beta}-GA dose-dependently (1-40 {mu}M) significantly decreased lipid accumulation in maturing preadipocytes. In 3T3-L1 preadipocytes, 10 {mu}M of 18{beta}-GA down-regulated the transcriptional levels of the peroxisome proliferator-activated receptor {gamma}, CCAAT/enhancer-binding protein {alpha} and adiponectin, which are markers of adipogenic differentiation via Akt phosphorylation. Also, in differentiated adipocytes, 18{beta}-GA increased the level of glycerol release and up-regulated the mRNA of hormone-sensitive lipase, adipose TG lipase and perilipin, as well as the phosphorylation of hormone-sensitive lipase at Serine 563. The results indicate that 18{beta

  20. Coupling in vitro gastrointestinal lipolysis and Caco-2 cell cultures for testing the absorption of different food emulsions.

    Science.gov (United States)

    Vors, Cécile; Capolino, Perrine; Guérin, Clémence; Meugnier, Emmanuelle; Pesenti, Sandra; Chauvin, Marie-Agnès; Monteil, Julien; Peretti, Noël; Cansell, Maud; Carrière, Frédéric; Michalski, Marie-Caroline

    2012-05-01

    There is a growing interest in the optimization of dietary emulsions for monitoring postprandial lipid metabolism in the frame of preventing metabolic diseases. Using various emulsions, we investigated in a systematic scheme the combination of (i) in vitro gastrointestinal lipolysis and (ii) absorption and metabolism of lipolysis media in Caco-2 cells. Four emulsions based on either milk fat olein (OL) or rapeseed oil (RA) as the dispersed phase and either lecithin (LE) or sodium caseinate (CA) as the emulsifier were tested. After a sequential incubation of these emulsions with gastric and pancreatic enzymes, lipolysis media were incubated with Caco-2 cells, after dilution (1 : 20) to maintain the barrier integrity. Both gastric and duodenal lipolysis levels were similar to values reported in vivo and the rates of lipolysis were higher with LE-stabilized emulsions than with CA-stabilized emulsions (P < 0.05). TAG secretion by Caco-2 cells was found to be higher using (i) duodenal vs. gastric media (P < 0.001) and (ii) emulsions stabilized with CA vs. LE (P < 0.01). Consistently, gene expression of both FABP2 and FATP4 induced by the duodenal media was (i) higher than that with gastric media (P < 0.001) and (ii) faster than that with model mixed micelles. Using gastric media, TAG secretion of Caco-2 cells after 12 h was higher with RA than with OL (P < 0.001). Moreover, the RA-CA emulsion increased the size of secreted lipoprotein particles (514 nm vs. 61 to 130 nm; P < 0.01). In conclusion, it was possible to observe distinct responses in the lipid metabolism of Caco-2 cells incubated with lipolysis media obtained from different dietary emulsions digested by gastrointestinal lipases in vitro.

  1. B56alpha/protein phosphatase 2A inhibits adipose lipolysis in high-fat diet-induced obese mice.

    Science.gov (United States)

    Kinney, Brice P; Qiao, Liping; Levaugh, Justin M; Shao, Jianhua

    2010-08-01

    Lipolysis and lipogenesis are two opposite processes that control lipid storage in adipocytes. Impaired adipose lipolysis has been observed in both obese human subjects and animal models. This study investigated the mechanisms underlying impaired adipose lipolysis in a high-fat diet-induced obese (DIO) mouse model. DIO models were created using male C57BL/6 mice. Our results show that beta3 adrenergic receptor-specific agonist BRL37344 induced adipose lipolysis was significantly blunted in DIO mice. The levels of Ser660 phosphorylation of hormone-sensitive lipase (HSL) were significantly decreased in the epididymal fat of DIO mice. However, protein levels of HSL, adipose triglyceride lipase and its coactivator comparative gene identification-58 were similar between DIO and control mice. It is known that upon lipolytic hormone stimulation, protein kinase A phosphorylates HSL Ser660 and activates HSL, whereas protein phosphatase 2A (PP2A) dephosphorylates and inactivates HSL. Interestingly, our study shows that high-fat feeding did not alter epididymal fat cAMP and protein kinase A protein levels but significantly increased the expression of the alpha-isoform of PP2A regulatory subunit B' (B56alpha). To study the role of B56alpha in obesity-associated lipolytic defect, B56alpha was overexpressed or knocked down by adenovirus-mediated gene transduction in cultured 3T3-L1CARDelta1 adipocytes. Overexpression of B56alpha significantly decreased HSL Ser660 phosphorylation. In contrast, knocking down B56alpha increased hormone-stimulated HSL activation and lipolysis in mature 3T3-L1CARDelta1 adipocytes. These results strongly suggest that elevated B56alpha/PP2A inhibits HSL and lipolysis in white adipose tissue of DIO mice.

  2. Angiopoietin-like 4 (Angptl4) protein is a physiological mediator of intracellular lipolysis in murine adipocytes.

    Science.gov (United States)

    Gray, Nora E; Lam, Lily N; Yang, Karen; Zhou, Anna Y; Koliwad, Suneil; Wang, Jen-Chywan

    2012-03-09

    Intracellular triacylglycerol (TG) hydrolysis and fatty acid release by the white adipose tissue (WAT) during a fast is stimulated by counter-regulatory factors acting in concert, although how adipocytes integrate these lipolytic inputs is unknown. We tested the role of angiopoietin-like 4 (Angptl4), a secreted protein induced by fasting or glucocorticoid treatment, in modulating intracellular adipocyte lipolysis. Glucocorticoid receptor blockade prevented fasting-induced tissue Angptl4 expression and WAT TG hydrolysis in mice, and TG hydrolysis induced by fasts of 6 or 24 h was greatly reduced in mice lacking Angptl4 (Angptl4(-/-)). Glucocorticoid treatment mimicked the lipolytic effects of fasting, although with slower kinetics, and this too required Angptl4. Thus, fasting-induced WAT TG hydrolysis requires glucocorticoid action and Angptl4. Both fasting and glucocorticoid treatment also increased WAT cAMP levels and downstream phosphorylation of lipolytic enzymes. Angptl4 deficiency markedly reduced these effects, suggesting that Angptl4 may stimulate lipolysis by modulating cAMP-dependent signaling. In support of this, cAMP levels and TG hydrolysis were reduced in primary Angptl4(-/-) murine adipocytes treated with catecholamines, which stimulate cAMP-dependent signaling to promote lipolysis, and was restored by treatment with purified human ANGPTL4. Remarkably, human ANGPTL4 treatment alone increased cAMP levels and induced lipolysis in these cells. Pharmacologic agents revealed that Angptl4 modulation of cAMP-dependent signaling occurs upstream of adenylate cyclase and downstream of receptor activation. We show that Angptl4 is a glucocorticoid-responsive mediator of fasting-induced intracellular lipolysis and stimulates cAMP signaling in adipocytes. Such a role is relevant to diseases of aberrant lipolysis, such as insulin resistance.

  3. Effect of milk pasteurization on lipolysis during ripening of ovine cheese manufactured at different times of the year

    OpenAIRE

    Chávarri, Felisa; Angeles Bustamante, M.; Santisteban, Arantza; Virto, Mailo; Albisu, Marta; Barrón, Luis; De Renobales, Mertxe

    2000-01-01

    International audience; Lipolysis was studied in cheeses manufactured with pasteurized and raw ovine milk with a starter culture added in winter, spring and summer, up to 180 d of ripening. Pasteurized milk cheeses had significantly lower levels of lipolysis than raw milk cheeses in winter after 180 d of ripening and in spring both after 90 and 180 d of ripening. The relative amounts of individual FFA after 180 d of ripening changed from winter to summer, both in pasteurized and in raw milk c...

  4. Increase or Decrease Hydrogen Sulfide Exert Opposite Lipolysis, but Reduce Global Insulin Resistance in High Fatty Diet Induced Obese Mice

    OpenAIRE

    Bin Geng; Bo Cai; Feng Liao; Yang Zheng; Qiang Zeng; Xiaofang Fan; Yongsheng Gong; Jichun Yang; Qing Hua Cui; Chaoshu Tang; Guo Heng Xu

    2013-01-01

    OBJECTIVE: Adipose tissue expressed endogenous cystathionine gamma lyase (CSE)/hydrogen sulfide (H2S) system. H2S precursor inhibited catecholamine stimulated lipolysis. Thus, we hypothesized that CSE/H2S system regulates lipolysis which contributed to the pathogenesis of insulin resistance. METHODS: We treated rat adipocyte with DL-propargylglycine (PAG, a CSE inhibitor), L-cysteine (an H2S precursor) plus pyridoxial phosphate (co-enzyme) or the H2S chronic release donor GYY4137, then the gl...

  5. Adipose tissue lipolysis is increased during a repeated bout of aerobic exercise.

    Science.gov (United States)

    Stich, V; de Glisezinski, I; Berlan, M; Bulow, J; Galitzky, J; Harant, I; Suljkovicova, H; Lafontan, M; Rivière, D; Crampes, F

    2000-04-01

    The goal of the study was to examine whether lipid mobilization from adipose tissue undergoes changes during repeated bouts of prolonged aerobic exercise. Microdialysis of the subcutaneous adipose tissue was used for the assessment of lipolysis; glycerol concentration was measured in the dialysate leaving the adipose tissue. Seven male subjects performed two repeated bouts of 60-min exercise at 50% of their maximal aerobic power, separated by a 60-min recovery period. The exercise-induced increases in extracellular glycerol concentrations in adipose tissue and in plasma glycerol concentrations were significantly higher during the second exercise bout compared with the first (P < 0.05). The responses of plasma nonesterified fatty acids and plasma epinephrine were higher during the second exercise bout, whereas the response of norepinephrine was unchanged and that of growth hormone lower. Plasma insulin levels were lower during the second exercise bout. The results suggest that adipose tissue lipolysis during aerobic exercise of moderate intensity is enhanced when an exercise bout is preceded by exercise of the same intensity and duration performed 1 h before. This response pattern is associated with an increase in the exercise-induced rise of epinephrine and with lower plasma insulin values during the repeated exercise bout.

  6. Effect of endurance training on adrenergic control of lipolysis in adipose tissue of obese women.

    Science.gov (United States)

    Richterova, B; Stich, V; Moro, C; Polak, J; Klimcakova, E; Majercik, M; Harant, I; Viguerie, N; Crampes, F; Langin, D; Lafontan, M; Berlan, M

    2004-03-01

    The effect of a 12-wk training program on sc abdominal adipose tissue (SCAAT) was studied in 11 obese women. Before and after the training, biopsies of SCAAT were performed for mRNA levels determination. Using the microdialysis method, involvement of alpha(2)- and beta-adrenergic receptor (ARs) in the control of lipolysis in SCAAT was studied using local perfusion of epinephrine alone or supplemented with phentolamine, an alpha(2)-AR antagonist. In addition, the variation in dialysate glycerol concentrations during exercise (50% peak oxygen consumption at 40 min) in a probe perfused with Ringer's solution was compared with that obtained in a probe perfused with Ringer's solution plus phentolamine. Training did not promote changes in the expression of key genes of the lipolytic pathway. The epinephrine-induced rise in the dialysate glycerol concentration was identical before and after training and was similarly potentiated by phentolamine. During exercise, the potentiating effect of phentolamine on the glycerol response was apparent before, but not after, training. The exercise-induced increase in plasma norepinephrine was lower after training (P = 0.04). In conclusion, training did not modify either the expression of genes involved in the control of lipolysis or alpha(2)- and beta-ARs in situ sensitivity to epinephrine in SCAAT. Training reduced the antilipolytic action of catecholamines mediated by alpha(2)-ARs during exercise, probably due to a reduction of exercise-induced catecholamine increase.

  7. Glucose-dependent insulinotropic polypeptide induces cytokine expression, lipolysis, and insulin resistance in human adipocytes.

    Science.gov (United States)

    Timper, Katharina; Grisouard, Jean; Sauter, Nadine S; Herzog-Radimerski, Tanja; Dembinski, Kaethi; Peterli, Ralph; Frey, Daniel M; Zulewski, Henryk; Keller, Ulrich; Müller, Beat; Christ-Crain, Mirjam

    2013-01-01

    Obesity-related insulin resistance is linked to a chronic state of systemic and adipose tissue-derived inflammation. Glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone also acting on adipocytes. We investigated whether GIP affects inflammation, lipolysis, and insulin resistance in human adipocytes. Human subcutaneous preadipocyte-derived adipocytes, differentiated in vitro, were treated with human GIP to analyze mRNA expression and protein secretion of cytokines, glycerol, and free fatty acid release and insulin-induced glucose uptake. GIP induced mRNA expression of IL-6, IL-1β, and the IL-1 receptor antagonist IL-1Ra, whereas TNFα, IL-8, and monocyte chemotactic protein (MCP)-1 remained unchanged. Cytokine induction involved PKA and the NF-κB pathway as well as an autocrine IL-1 effect. Furthermore, GIP potentiated IL-6 and IL-1Ra secretion in the presence of LPS, IL-1β, and TNFα. GIP induced lipolysis via activation of hormone-sensitive lipase and was linked to NF-κB activation. Finally, chronic GIP treatment impaired insulin-induced glucose uptake possibly due to the observed impaired translocation of glucose transporter GLUT4. In conclusion, GIP induces an inflammatory and prolipolytic response via the PKA -NF-κB-IL-1 pathway and impairs insulin sensitivity of glucose uptake in human adipocytes.

  8. Lipolysis index: evaluation of a new tool for metabolic assessment in epidemiological studies on obesity.

    Science.gov (United States)

    Leijonhufvud, B-M; Hertel, K; Löfgren, P

    2010-12-01

    Lipid mobilization through adipocyte lipolysis is central for energy metabolism and is decreased in obesity. However, the factors of importance for lipolytic activity in the general population are not known. To further examine this we performed a cross-sectional study on teenagers and adults. We constructed and evaluated a simple index of lipolytic activity (ratio of fasting p-glycerol and body fat %) in population based samples in 316 teenagers (BMI 16-51 kg/m (2)) and 3,039 adults (BMI 16-70 kg/m (2)). In the adults, multiple regression analysis showed that waist and BMI but not age, plasma insulin, plasma noradrenaline or waist-to-hip ratio contributed independently and inversely to lipolytic activity (partial r=-0.37 and -0.28, respectively, plipolysis. Waist was a stronger factor than BMI in stepwise regression. The same analysis in teenagers showed that only BMI contributed independently and inversely to lipolytic activity (partial r=-0.90, plipolysis variation. BMI had the strongest effect on lipolysis in lean teenagers. The results were the same for men and women. At all levels of lipolytic activity plasma fatty acid levels were elevated in obese subjects (plipolysis. In spite of low lipolytic activity circulating fatty acid levels are increased in obesity, probably due to an adipose mass effect. © Georg Thieme Verlag KG Stuttgart · New York.

  9. Melanocortin agonists stimulate lipolysis in human adipose tissue explants but not in adipocytes.

    Science.gov (United States)

    Møller, Cathrine Laustrup; Pedersen, Steen B; Richelsen, Bjørn; Conde-Frieboes, Kilian W; Raun, Kirsten; Grove, Kevin L; Wulff, Birgitte Schjellerup

    2015-10-12

    The central melanocortin system is broadly involved in the regulation of mammalian nutrient utilization. However, the function of melanocortin receptors (MCRs) expressed directly in peripheral metabolic tissues is still unclear. The objective of this study was to investigate the lipolytic capacity of MC1-5R in differentiated adipocytes versus intact white adipose tissue. Non-selective MCR agonist α-MSH, MC5R-selective agonist PG-901 and MC4R-selective agonist LY2112688 significantly stimulated lipolysis in intact white adipose tissue, whereas stimulation of MCRs in differentiated adipocytes failed to do so. The lipolytic response of MC5R was decreased in intact human white adipose tissue when co-treating with β-adrenergic antagonist propranolol, suggesting that the effect may be dependent on neuronal innervation via noradrenalin release. When developing an anti-obesity therapeutic drug with selective MC4R/MC5R properties, effects on lipolysis in white adipose tissue may be physiologically relevant.

  10. Genetic control of ATGL-mediated lipolysis modulates adipose triglyceride stores in leptin-deficient mice.

    Science.gov (United States)

    Marcelin, Genevieve; Liu, Shun-Mei; Li, Xiaosong; Schwartz, Gary J; Chua, Streamson

    2012-05-01

    Dissecting the genetics of complex traits such as obesity allows the identification of causal genes for disease. Here, we show that the BALB/c mouse strain carries genetic variants that confer resistance to obesity induced by leptin-deficiency or a high-fat diet (HFD). We set out to identify the physiological and genetic bases underlying this phenotype. When compared with C57BL6/J ob/ob mice (B6), BALB/c ob/ob mice exhibited decreased food intake, increased thermogenic capacity, and improved fat catabolism, each of which can potentially modify obesity. Interestingly, analysis of F1 ob/ob (progeny of B6 ob/+ × BALB/c ob+) mice revealed that obesity resistance in BALB/c ob/ob mice principally relied upon improved fat mobilization. This was mechanistically explained by increased adipose triglyceride lipase (ATGL) content in adipocytes, along with increased lipolysis and fatty acid oxidation. We conducted a genome-wide scan and defined a quantitative trait locus (QTL) on chromosome 2. BALB/c alleles on chromosome 2 not only associated with the obesity resistance phenotype but also supported increased ATGL content in adipose tissue. In summary, our study provides evidence that leptin-independent control of adipocyte lipolysis rates directly modifies the balance of macronutrient handling and is sufficient to regulate fat mass in the absence of alterations in food intake and energy expenditure.-Marcelin, G., S-M. Liu, X. Li, G. J. Schwartz, and S. Chua.

  11. Polygonatum stenophyllum improves menopausal obesity via regulation of lipolysis-related enzymes.

    Science.gov (United States)

    Lee, Ji Eun; Kim, Eun-Jung; Kim, Mi Hye; Hong, Jongki; Yang, Woong Mo

    2016-10-01

    Menopausal women are associated with an increase in obesity accompanying changes in the body's condition and composition. Polygonatum stenophyllum (PS) rhizome, which is a traditional herbal remedy, has been used to treat various diseases including obesity. However, the effect of PS on menopausal obesity remains unclear. Female C57BL/6 mice were ovariectomized (OVX) and fed on high fat diet (HFD) to induce menopausal obesity. Aqueous extract of PS of 1, 10, and 100 mg/kg was orally administrated for 6 weeks after 7 weeks of induction. The weights of body, uterine, and ovarian fat were investigated. Histological analysis was performed to monitor the changes of liver and fat. In addition, lipid profiles were measured in serum and the expression of lipolysis-related enzymes was analyzed in uterine tissues. PS significantly decreased the weights of body and ovarian fat and increased the uterine weight compared to control group. Administration of PS significantly decreased the adipocyte diameter and the lipid droplets within the hepatocytes. In addition, PS-treated mice had lower levels of triglyceride (TG), total cholesterol, and LDL-cholesterol than control mice. The expression of lipolysis-related genes, including adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), was increased in PS-treated groups. Taken together, these results demonstrate that PS might have efficacy on menopausal obesity by activating ATGL and HSL.

  12. Use of a novel combined radiofrequency and ultrasound device for lipolysis, skin tightening and cellulite treatment.

    Science.gov (United States)

    Kapoor, Rinky; Shome, Debraj; Ranjan, Anima

    2017-03-10

    Skin laxity and excessive subcutaneous fat are growing cosmetic concerns. The objective of this study is to evaluate the efficacy and safety of a novel radiofrequency and ultrasound workstation for lipolysis, circumference reduction, treatment of skin laxity and cellulite. Two hundred seventy-five (235 women and 40 men) patients were enrolled into the study. Each patient received 3 treatment sessions, each session comprising Ultrasound and Radiofrequency treatments, at two-week intervals. Some received treatment for the abdomen, some for the thighs and some for both. Efficacy was assessed accordingly by measuring changes in abdominal circumference, thigh circumference and appearance of cellulite. Any adverse effect was noted. Paired t-test between measurements at baseline and 4 weeks after 3rd session was significant amongst all the groups, showing that most patients showed improvement in abdominal and/or thigh circumferences. No significant adverse effects were noted during or after the treatment. A combination of alternating hot and cold module Ultrasound and Radiofrequency technologies is a safe and effective modality for lipolysis and to treat skin laxity and cellulite.

  13. The lipolysis pathway sustains normal and transformed stem cells in adult Drosophila.

    Science.gov (United States)

    Singh, Shree Ram; Zeng, Xiankun; Zhao, Jiangsha; Liu, Ying; Hou, Gerald; Liu, Hanhan; Hou, Steven X

    2016-10-06

    Cancer stem cells (CSCs) may be responsible for tumour dormancy, relapse and the eventual death of most cancer patients. In addition, these cells are usually resistant to cytotoxic conditions. However, very little is known about the biology behind this resistance to therapeutics. Here we investigated stem-cell death in the digestive system of adult Drosophila melanogaster. We found that knockdown of the coat protein complex I (COPI)-Arf79F (also known as Arf1) complex selectively killed normal and transformed stem cells through necrosis, by attenuating the lipolysis pathway, but spared differentiated cells. The dying stem cells were engulfed by neighbouring differentiated cells through a draper-myoblast city-Rac1-basket (also known as JNK)-dependent autophagy pathway. Furthermore, Arf1 inhibitors reduced CSCs in human cancer cell lines. Thus, normal or cancer stem cells may rely primarily on lipid reserves for energy, in such a way that blocking lipolysis starves them to death. This finding may lead to new therapies that could help to eliminate CSCs in human cancers.

  14. Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals.

    Science.gov (United States)

    Zhou, Hongyi; Lei, Xinnuo; Benson, Tyler; Mintz, James; Xu, Xiaojing; Harris, Ruth B; Weintraub, Neal L; Wang, Xiaoling; Chen, Weiqin

    2015-10-01

    Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat diet-induced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counter-regulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in Ad-mKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance. Copyright © 2015 by the American Society for Biochemistry and Molecular Biology, Inc.

  15. Hormonal control of lipolysis from the white adipose tissue of hibernating jerboa (Jaculus orientalis).

    Science.gov (United States)

    Moreau-Hamsany, C; Castex, C; Hoo-Paris, R; Kacemi, N; Sutter, B

    1988-01-01

    1. Plasma glucose, glycerol, free fatty acids and total lipid content of the white adipose tissue were measured in euthermic and hibernating jerboa. 2. During hibernation, plasma glucose and glycerol were low compared to the euthermic animals, whereas there was no obvious difference in plasma free fatty acids. The white adipose tissue lipid content was strongly reduced in the hibernating state. 3. The effect of lipolytic hormones (norepinephrine and glucagon) and antilipolytic hormone (insulin) on in vitro glycerol release by adipose tissue isolated from hibernating or euthermic jerboa has been studied. 4. The white adipose tissue from hibernating jerboa presented a higher sensitivity to norepinephrine and glucagon than that of euthermic jerboa; insulin did not modify either basal glycerol release or lipolysis induced by the two lipolytic hormones at low temperatures (7 degrees C) and during the rewarming (from 7 degrees C to 37 degrees C) of the tissue slices. 5. These results suggested that white adipose tissue constitutes an important source of substrates derived from lipolysis during hibernation.

  16. Leucaena leucocephala fruit aqueous extract stimulates adipogenesis, lipolysis, and glucose uptake in primary rat adipocytes.

    Science.gov (United States)

    Kuppusamy, Umah Rani; Arumugam, Bavani; Azaman, Nooriza; Jen Wai, Chai

    2014-01-01

    Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro "insulin-like" activities of Leucaena leucocephala (Lam.) deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1) involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

  17. Leucaena leucocephala Fruit Aqueous Extract Stimulates Adipogenesis, Lipolysis, and Glucose Uptake in Primary Rat Adipocytes

    Directory of Open Access Journals (Sweden)

    Umah Rani Kuppusamy

    2014-01-01

    Full Text Available Leucaena leucocephala had been traditionally used to treat diabetes. The present study was designed to evaluate in vitro “insulin-like” activities of Leucaena leucocephala (Lam. deWit. aqueous fruit extract on lipid and glucose metabolisms. The ability of the extract to stimulate adipogenesis, inhibit lipolysis, and activate radio-labeled glucose uptake was assessed using primary rat adipocytes. Quantitative Real-Time RT-PCR was performed to investigate effects of the extract on expression levels of genes (protein kinases B, AKT; glucose transporter 4, GLUT4; hormone sensitive lipase, HSL; phosphatidylinositol-3-kinases, PI3KA; sterol regulatory element binding factor 1, Srebp1 involved in insulin-induced signaling pathways. L. leucocephala aqueous fruit extract stimulated moderate adipogenesis and glucose uptake into adipocytes when compared to insulin. Generally, the extract exerted a considerable level of lipolytic effect at lower concentration but decreased gradually at higher concentration. The findings concurred with RT-PCR analysis. The expressions of GLUT4 and HSL genes were upregulated by twofold and onefold, respectively, whereas AKT, PI3KA, and Srebp1 genes were downregulated. The L. leucocephala aqueous fruit extract may be potentially used as an adjuvant in the treatment of Type 2 diabetes mellitus and weight management due to its enhanced glucose uptake and balanced adipogenesis and lipolysis properties.

  18. Are blood flow and lipolysis in subcutaneous adipose tissue influenced by contractions in adjacent muscles in humans?

    DEFF Research Database (Denmark)

    Stallknecht, Bente; Dela, Flemming; Helge, Jørn Wulff

    2006-01-01

    Aerobic exercise increases whole body adipose tissue lipolysis, but is lipolysis higher in subcutaneous adipose tissue (SCAT) adjacent to contracting muscles than in SCAT adjacent to resting muscles? Ten healthy, overnight-fasted males performed one-legged knee extension exercise at 25% of maximal...... workload (W(max)) for 30 min followed by exercise at 55% W(max) for 120 min with the other leg and finally exercised at 85% W(max) for 30 min with the first leg. Subjects rested for 30 min between exercise periods. Femoral SCAT blood flow was estimated from washout of (133)Xe, and lipolysis was calculated...... from femoral SCAT interstitial and arterial glycerol concentrations and blood flow. In general, blood flow and lipolysis were higher in femoral SCAT adjacent to contracting than adjacent to resting muscle (time 15-30 min; blood flow: 25% W(max) 6.6 +/- 1.0 vs. 3.9 +/- 0.8 ml x 100 g(-1) x min(-1), P...

  19. Ablation of a galectin preferentially expressed in adipocytes increases lipolysis, reduces adiposity, and improves insulin sensitivity in mice.

    Science.gov (United States)

    Yang, Ri-Yao; Yu, Lan; Graham, James L; Hsu, Daniel K; Lloyd, K C Kent; Havel, Peter J; Liu, Fu-Tong

    2011-11-15

    The breakdown of triglycerides, or lipolysis, is a tightly controlled process that regulates fat mobilization in accord with an animal's energy needs. It is well established that lipolysis is stimulated by hormones that signal energy demand and is suppressed by the antilipolytic hormone insulin. However, much still remains to be learned about regulation of lipolysis by intracellular signaling pathways in adipocytes. Here we show that galectin-12, a member of a β-galactoside-binding lectin family preferentially expressed by adipocytes, functions as an intrinsic negative regulator of lipolysis. Galectin-12 is primarily localized on lipid droplets and regulates lipolytic protein kinase A signaling by acting upstream of phosphodiesterase activity to control cAMP levels. Ablation of galectin-12 in mice results in increased adipocyte mitochondrial respiration, reduced adiposity, and ameliorated insulin resistance/glucose intolerance. This study identifies unique properties of this intracellular galectin that is localized to an organelle and performs a critical function in lipid metabolism. These findings add to the significant functions exhibited by intracellular galectins, and have important therapeutic implications for human metabolic disorders.

  20. Insulin resistance and increased lipolysis in bone marrow derived adipocytes stimulated with agonists of Toll-like receptors.

    Science.gov (United States)

    Franchini, M; Monnais, E; Seboek, D; Radimerski, T; Zini, E; Kaufmann, K; Lutz, T; Reusch, C; Ackermann, M; Muller, B; Linscheid, P

    2010-09-01

    Our objectives were to identify Toll-like receptors (TLRs) in human bone marrow derived adipocytes, to test specific TLR agonists for their ability to induce a proinflammatory response, and to investigate possible metabolic effects after TLR activation, in particular, those associated with insulin resistance and lipolysis. Mesenchymal stem cells were isolated from human bone marrow and differentiated into adipocytes. Total RNA before or after stimulation with agonists specific for TLR was extracted for analysis of expression of TLRs proinflammatory signals and molecules involved in glucose metabolism (IRS-1 and GLUT4). Furthermore, cytokine protein expression was measured from cell lysates. Finally, insulin induced glucose uptake and lipolysis were measured. Human bone marrow-derived adipocytes express TLR1-10. They react to stimulation with specific ligands with expression of inflammatory markers (IL-1beta, IL-6, TNFalpha, IL-8, MCP-1) at the RNA and protein levels. IRS-1 and GLUT4 expression was downregulated after stimulation with the TLR4 and TLR3 specific ligands LPS and poly (I:C), respectively. Insulin-induced glucose uptake was decreased and lipolysis increased. We conclude that adipocytes express TLR 1-10 and react to agonists specific for TLR 1-6. As a consequence proinflammatory cytokine are induced, in particular, IL-6, IL-8, and MCP-1. Since stimulation is followed by decreased insulin-induced glucose uptake and increased lipolysis we conclude that TLRs may be important linking molecules in the generation of insulin resistance in fat tissue.

  1. Reactive oxygen species facilitate translocation of hormone sensitive lipase to the lipid droplet during lipolysis in human differentiated adipocytes.

    Directory of Open Access Journals (Sweden)

    Sarah A Krawczyk

    Full Text Available In obesity, there is an increase in reactive oxygen species (ROS within adipose tissue caused by increases in inflammation and overnutrition. Hormone sensitive lipase (HSL is part of the canonical lipolytic pathway and critical for complete lipolysis. This study hypothesizes that ROS is a signal that integrates regulation of lipolysis by targeting HSL. Experiments were performed with human differentiated adipocytes from the subcutaneous depot. Antioxidants were employed as a tool to decrease ROS, and it was found that scavenging ROS with diphenyliodonium, N-acetyl cysteine, or resveratrol decreased lipolysis in adipocytes. HSL phosphorylation of a key serine residue, Ser552, as well as translocation of this enzyme from the cytosol to the lipid droplet upon lipolytic stimulation were both abrogated by scavenging ROS. The phosphorylation status of other serine residues on HSL were not affected. These findings are significant because they document that ROS contributes to the physiological regulation of lipolysis via an effect on translocation. Such regulation could be useful in developing new obesity therapies.

  2. Curcumin attenuates lipolysis stimulated by tumor necrosis factor-α or isoproterenol in 3T3-L1 adipocytes.

    Science.gov (United States)

    Xie, Xiao-yun; Kong, Po-Ren; Wu, Jin-feng; Li, Ying; Li, Yan-xiang

    2012-12-15

    Curcumin, an active component derived from dietary spice turmeric (Curcuma longa), has been demonstrated antihyperglycemic, antiinflammatory and hypocholesterolemic activities in obesity and diabetes. These effects are associated with decreased level of circulating free fatty acids (FFA), however the mechanism has not yet been elucidated. The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-α (TNFα) stimulates chronic lipolysis in obesity and type 2 diabetes. In this study, we examined the role of curcumin in inhibiting lipolytic action upon various stimulations in 3T3-L1 adipocytes. Glycerol release from TNFα or isoproterenol-stimulated 3T3-L1 adipocytes in the absence or presence of curcumin was determined using a colorimetric assay (GPO-Trinder). Western blotting was used to investigate the TNFα-induced phosphorylation of MAPK and perilipin expression. Fatcake and cytosolic fractions were prepared to examine the isoproterenol-stimulated hormone-sensitive lipase translocation. Treatment with curcumin attenuated TNFα-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 (ERK1/2) and reversing the downregulation of perilipin protein in TNFα-stimulated adipocytes (plipolysis response to TNFα and catecholamines. The antilipolytic effect could be a cellular basis for curcumin decreasing plasma FFA levels and improving insulin sensitivity. Copyright © 2012 Elsevier GmbH. All rights reserved.

  3. AdPLA ablation increases lipolysis and prevents obesity induced by high fat feeding or leptin deficiency

    Science.gov (United States)

    Jaworski, Kathy; Ahmadian, Maryam; Duncan, Robin E.; Sarkadi-Nagy, Eszter; Varady, Krista A.; Hellerstein, Marc K.; Lee, Hui-Young; Samuel, Varman T.; Shulman, Gerald I.; Kim, Kee-Hong; de Val, Sarah; Kang, Chulho; Sul, Hei Sook

    2010-01-01

    A main function of white adipose tissue is to release fatty acids from triacylglycerol for other tissues to use as an energy source. While endocrine regulation of lipolysis has been extensively studied, autocrine/paracrine regulation is not well understood. Here, we describe the role of AdPLA, the newly identified major adipocyte phospholipase A2, in the regulation of lipolysis and adiposity. AdPLA null mice have a markedly higher rate of lipolysis, due to increased cAMP levels arising from the marked reduction in adipose PGE2 that binds the Gαi-coupled receptor, EP3. AdPLA null mice have drastically reduced adipose tissue mass and triglyceride content, with normal adipogenesis. They also have higher energy expenditure with higher fatty acid oxidation within adipocytes. AdPLA deficient ob/ob mice remain hyperphagic but lean, with increased energy expenditure, yet have ectopic triglyceride storage and insulin resistance. AdPLA is a major regulator of adipocyte lipolysis and critical for the development of obesity. PMID:19136964

  4. Reactive oxygen species facilitate translocation of hormone sensitive lipase to the lipid droplet during lipolysis in human differentiated adipocytes.

    Science.gov (United States)

    Krawczyk, Sarah A; Haller, Jorge F; Ferrante, Tom; Zoeller, Raphael A; Corkey, Barbara E

    2012-01-01

    In obesity, there is an increase in reactive oxygen species (ROS) within adipose tissue caused by increases in inflammation and overnutrition. Hormone sensitive lipase (HSL) is part of the canonical lipolytic pathway and critical for complete lipolysis. This study hypothesizes that ROS is a signal that integrates regulation of lipolysis by targeting HSL. Experiments were performed with human differentiated adipocytes from the subcutaneous depot. Antioxidants were employed as a tool to decrease ROS, and it was found that scavenging ROS with diphenyliodonium, N-acetyl cysteine, or resveratrol decreased lipolysis in adipocytes. HSL phosphorylation of a key serine residue, Ser552, as well as translocation of this enzyme from the cytosol to the lipid droplet upon lipolytic stimulation were both abrogated by scavenging ROS. The phosphorylation status of other serine residues on HSL were not affected. These findings are significant because they document that ROS contributes to the physiological regulation of lipolysis via an effect on translocation. Such regulation could be useful in developing new obesity therapies.

  5. Adipose-selective overexpression of ABHD5/CGI-58 does not increase lipolysis or protect against diet-induced obesity.

    Science.gov (United States)

    Caviglia, Jorge M; Betters, Jenna L; Dapito, Dianne-Helerie; Lord, Caleb C; Sullivan, Sean; Chua, Streamson; Yin, Terry; Sekowski, Anna; Mu, Haiyan; Shapiro, Lawrence; Brown, J Mark; Brasaemle, Dawn L

    2011-11-01

    Adipose triglyceride lipase (ATGL) catalyzes the first step of triacylglycerol hydrolysis in adipocytes. Abhydrolase domain 5 (ABHD5) increases ATGL activity by an unknown mechanism. Prior studies have suggested that the expression of ABHD5 is limiting for lipolysis in adipocytes, as addition of recombinant ABHD5 increases in vitro TAG hydrolase activity of adipocyte lysates. To test this hypothesis in vivo, we generated transgenic mice that express 6-fold higher ABHD5 in adipose tissue relative to wild-type (WT) mice. In vivo lipolysis increased to a similar extent in ABHD5 transgenic and WT mice following an overnight fast or injection of either a β-adrenergic receptor agonist or lipopolysaccharide. Similarly, basal and β-adrenergic-stimulated lipolysis was comparable in adipocytes isolated from ABHD5 transgenic and WT mice. Although ABHD5 expression was elevated in thioglycolate-elicited macrophages from ABHD5 transgenic mice, Toll-like receptor 4 (TLR4) signaling was comparable in macrophages isolated from ABHD5 transgenic and WT mice. Overexpression of ABHD5 did not prevent the development of obesity in mice fed a high-fat diet, as shown by comparison of body weight, body fat percentage, and adipocyte hypertrophy of ABHD5 transgenic to WT mice. The expression of ABHD5 in mouse adipose tissue is not limiting for either basal or stimulated lipolysis.

  6. AdPLA ablation increases lipolysis and prevents obesity induced by high-fat feeding or leptin deficiency.

    Science.gov (United States)

    Jaworski, Kathy; Ahmadian, Maryam; Duncan, Robin E; Sarkadi-Nagy, Eszter; Varady, Krista A; Hellerstein, Marc K; Lee, Hui-Young; Samuel, Varman T; Shulman, Gerald I; Kim, Kee-Hong; de Val, Sarah; Kang, Chulho; Sul, Hei Sook

    2009-02-01

    A main function of white adipose tissue is to release fatty acids from stored triacylglycerol for other tissues to use as an energy source. Whereas endocrine regulation of lipolysis has been extensively studied, autocrine and paracrine regulation is not well understood. Here we describe the role of the newly identified major adipocyte phospholipase A(2), AdPLA (encoded by Pla2g16, also called HREV107), in the regulation of lipolysis and adiposity. AdPLA-null mice have a markedly higher rate of lipolysis owing to increased cyclic AMP levels arising from the marked reduction in the amount of adipose prostaglandin E(2) that binds the Galpha(i)-coupled receptor, EP3. AdPLA-null mice have markedly reduced adipose tissue mass and triglyceride content but normal adipogenesis. They also have higher energy expenditure with increased fatty acid oxidation within adipocytes. AdPLA-deficient ob/ob mice remain hyperphagic but lean, with increased energy expenditure, yet have ectopic triglyceride storage and insulin resistance. AdPLA is a major regulator of adipocyte lipolysis and is crucial for the development of obesity.

  7. Pik3r1 Is Required for Glucocorticoid-Induced Perilipin 1 Phosphorylation in Lipid Droplet for Adipocyte Lipolysis.

    Science.gov (United States)

    Kuo, Taiyi; Chen, Tzu-Chieh; Lee, Rebecca A; Nguyen, Nguyen Huynh Thao; Broughton, Augusta E; Zhang, Danyun; Wang, Jen-Chywan

    2017-06-01

    Glucocorticoids promote lipolysis in white adipose tissue (WAT) to adapt to energy demands under stress, whereas superfluous lipolysis causes metabolic disorders, including dyslipidemia and hepatic steatosis. Glucocorticoid-induced lipolysis requires the phosphorylation of cytosolic hormone-sensitive lipase (HSL) and perilipin 1 (Plin1) in the lipid droplet by protein kinase A (PKA). We previously identified Pik3r1 (also called p85α) as a glucocorticoid receptor target gene. Here, we found that glucocorticoids increased HSL phosphorylation, but not Plin1 phosphorylation, in adipose tissue-specific Pik3r1-null (AKO) mice. Furthermore, in lipid droplets, the phosphorylation of HSL and Plin1 and the levels of catalytic and regulatory subunits of PKA were increased by glucocorticoids in wild-type mice. However, these effects were attenuated in AKO mice. In agreement with reduced WAT lipolysis, glucocorticoid- initiated hepatic steatosis and hypertriglyceridemia were improved in AKO mice. Our data demonstrated a novel role of Pik3r1 that was independent of the regulatory function of phosphoinositide 3-kinase in mediating the metabolic action of glucocorticoids. Thus, the inhibition of Pik3r1 in adipocytes could alleviate lipid disorders caused by excess glucocorticoid exposure. © 2017 by the American Diabetes Association.

  8. Role of white adipose lipolysis in the development of NASH induced by methionine- and choline-deficient diet.

    Science.gov (United States)

    Tanaka, Naoki; Takahashi, Shogo; Fang, Zhong-Ze; Matsubara, Tsutomu; Krausz, Kristopher W; Qu, Aijuan; Gonzalez, Frank J

    2014-11-01

    Methionine- and choline-deficient diet (MCD) is a model for nonalcoholic steatohepatitis (NASH) in rodents. However, the mechanism of NASH development by dietary methionine/choline deficiency remains undetermined. To elucidate the early metabolic changes associated with MCD-NASH, serum metabolomic analysis was performed using mice treated with MCD and control diet for 3 days and 1 week, revealing significant increases in oleic and linoleic acids after MCD treatment. These increases were correlated with reduced body weight and white adipose tissue (WAT) mass, increased phosphorylation of hormone-sensitive lipase, and up-regulation of genes encoding carboxylesterase 3 and β2-adrenergic receptor in WAT, indicating accelerated lipolysis in adipocytes. The changes in serum fatty acids and WAT by MCD treatment were reversed by methionine supplementation, and similar alterations were detected in mice fed a methionine-deficient diet (MD), thus demonstrating that dietary methionine deficiency enhances lipolysis in WAT. MD treatment decreased glucose and increased fibroblast growth factor 21 in serum, thus exhibiting a similar metabolic phenotype as the fasting response. Comparison between MCD and choline-deficient diet (CD) treatments suggested that the addition of MD-induced metabolic alterations, such as WAT lipolysis, to CD-induced hepatic steatosis promotes liver injury. Collectively, these results demonstrate an important role for dietary methionine deficiency and WAT lipolysis in the development of MCD-NASH. Published by Elsevier B.V.

  9. High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering Drugs and Diet Network (GOLDN): an interventional study

    Science.gov (United States)

    Postprandial lipemia (PPL) is likely a risk factor for cardiovascular disease but these changes have not been well described and characterized in a large cohort. We assessed acute changes in the size and concentration of total and subclasses of LDL, HDL, and VLDL particles in response to a high-fat ...

  10. IL-15 concentrations in skeletal muscle and subcutaneous adipose tissue in lean and obese humans: local effects of IL-15 on adipose tissue lipolysis.

    Science.gov (United States)

    Pierce, Joseph R; Maples, Jill M; Hickner, Robert C

    2015-06-15

    Animal/cell investigations indicate that there is a decreased adipose tissue mass resulting from skeletal muscle (SkM) IL-15 secretion (e.g., SkM-blood-adipose tissue axis). IL-15 could regulate fat mass accumulation in obesity via lipolysis, although this has not been investigated in humans. Therefore, the purpose was to examine whether SkM and/or subcutaneous adipose tissue (SCAT) IL-15 concentrations were correlated with SCAT lipolysis in lean and obese humans and determine whether IL-15 perfusion could induce lipolysis in human SCAT. Local SkM and abdominal SCAT IL-15 (microdialysis) and circulating IL-15 (blood) were sampled in lean (BMI: 23.1 ± 1.9 kg/m(2); n = 10) and obese (BMI: 34.7 ± 3.5 kg/m(2); n = 10) subjects at rest/during 1-h cycling exercise. Lipolysis (SCAT interstitial glycerol concentration) was compared against local/systemic IL-15. An additional probe in SCAT was perfused with IL-15 to assess direct lipolytic responses. SkM IL-15 was not different between lean and obese subjects (P = 0.45), whereas SCAT IL-15 was higher in obese vs. lean subjects (P = 0.02) and was correlated with SCAT lipolysis (r = 0.45, P = 0.05). Exercise increased SCAT lipolysis in lean and obese (P lipolysis changes were not correlated with exercise-induced SCAT IL-15 changes. Microdialysis perfusion resulting in physiological IL-15 concentrations in the adipose tissue interstitium increased lipolysis in lean (P = 0.04) but suppressed lipolysis in obese (P < 0.01). Although we found no support for a human IL-15 SkM-blood-adipose tissue axis, IL-15 may be produced in/act on the abdominal SCAT depot. The extent to which this autocrine/paracrine IL-15 action regulates human body composition remains unknown. Copyright © 2015 the American Physiological Society.

  11. Trichostatin A Modulates Thiazolidinedione-Mediated Suppression of Tumor Necrosis Factor α-Induced Lipolysis in 3T3-L1 Adipocytes

    Science.gov (United States)

    Lu, Juu-Chin; Chang, Yu-Tzu; Wang, Chih-Tien; Lin, Yu-Chun; Lin, Chun-Ken; Wu, Zhong-Sheng

    2013-01-01

    In obesity, high levels of tumor necrosis factor α (TNFα) stimulate lipolysis in adipocytes, leading to hyperlipidemia and insulin resistance. Thiazolidinediones (TZDs), the insulin-sensitizing drugs, antagonize TNFα-induced lipolysis in adipocytes, thereby increasing insulin sensitivity in diabetes patients. The cellular target of TZDs is peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor that controls many adipocyte functions. As a transcription factor, PPARγ is closely modulated by coregulators, which include coactivators and corepressors. Previous studies have revealed that in macrophages, the insulin-sensitizing effect of PPARγ may involve suppression of proinflammatory gene expression by recruiting the corepressor complex that contains corepressors and histone deacetylases (HDACs). Therefore, we investigated whether the corepressor complex is involved in TZD-mediated suppression of TNFα-induced lipolysis in 3T3-L1 adipocytes. Trichostatin A (TSA), a pan HDAC inhibitor (HDACI) that inhibits class I and II HDACs, was used to examine the involvement of HDACs in the actions of TZDs. TSA alone increased basal lipolysis and attenuated TZD-mediated suppression of TNFα-induced lipolysis. Increased basal lipolysis may in part result from class I HDAC inhibition because selective class I HDACI treatment had similar results. However, attenuation of TZD-mediated TNFα antagonism may be specific to TSA and related hydroxamate-based HDACI rather than to HDAC inhibition. Consistently, corepressor depletion did not affect TZD-mediated suppression. Interestingly, TSA treatment greatly reduced PPARγ levels in differentiated adipocytes. Finally, extracellular signal-related kinase 1/2 (ERK1/2) mediated TNFα-induced lipolysis, and TZDs suppressed TNFα-induced ERK phosphorylation. We determined that TSA increased basal ERK phosphorylation, and attenuated TZD-mediated suppression of TNFα-induced ERK phosphorylation, consistent with TSA

  12. Trichostatin A modulates thiazolidinedione-mediated suppression of tumor necrosis factor α-induced lipolysis in 3T3-L1 adipocytes.

    Science.gov (United States)

    Lu, Juu-Chin; Chang, Yu-Tzu; Wang, Chih-Tien; Lin, Yu-Chun; Lin, Chun-Ken; Wu, Zhong-Sheng

    2013-01-01

    In obesity, high levels of tumor necrosis factor α (TNFα) stimulate lipolysis in adipocytes, leading to hyperlipidemia and insulin resistance. Thiazolidinediones (TZDs), the insulin-sensitizing drugs, antagonize TNFα-induced lipolysis in adipocytes, thereby increasing insulin sensitivity in diabetes patients. The cellular target of TZDs is peroxisome proliferator-activated receptor γ (PPARγ), a nuclear receptor that controls many adipocyte functions. As a transcription factor, PPARγ is closely modulated by coregulators, which include coactivators and corepressors. Previous studies have revealed that in macrophages, the insulin-sensitizing effect of PPARγ may involve suppression of proinflammatory gene expression by recruiting the corepressor complex that contains corepressors and histone deacetylases (HDACs). Therefore, we investigated whether the corepressor complex is involved in TZD-mediated suppression of TNFα-induced lipolysis in 3T3-L1 adipocytes. Trichostatin A (TSA), a pan HDAC inhibitor (HDACI) that inhibits class I and II HDACs, was used to examine the involvement of HDACs in the actions of TZDs. TSA alone increased basal lipolysis and attenuated TZD-mediated suppression of TNFα-induced lipolysis. Increased basal lipolysis may in part result from class I HDAC inhibition because selective class I HDACI treatment had similar results. However, attenuation of TZD-mediated TNFα antagonism may be specific to TSA and related hydroxamate-based HDACI rather than to HDAC inhibition. Consistently, corepressor depletion did not affect TZD-mediated suppression. Interestingly, TSA treatment greatly reduced PPARγ levels in differentiated adipocytes. Finally, extracellular signal-related kinase 1/2 (ERK1/2) mediated TNFα-induced lipolysis, and TZDs suppressed TNFα-induced ERK phosphorylation. We determined that TSA increased basal ERK phosphorylation, and attenuated TZD-mediated suppression of TNFα-induced ERK phosphorylation, consistent with TSA's effects

  13. Trichostatin A modulates thiazolidinedione-mediated suppression of tumor necrosis factor α-induced lipolysis in 3T3-L1 adipocytes.

    Directory of Open Access Journals (Sweden)

    Juu-Chin Lu

    Full Text Available In obesity, high levels of tumor necrosis factor α (TNFα stimulate lipolysis in adipocytes, leading to hyperlipidemia and insulin resistance. Thiazolidinediones (TZDs, the insulin-sensitizing drugs, antagonize TNFα-induced lipolysis in adipocytes, thereby increasing insulin sensitivity in diabetes patients. The cellular target of TZDs is peroxisome proliferator-activated receptor γ (PPARγ, a nuclear receptor that controls many adipocyte functions. As a transcription factor, PPARγ is closely modulated by coregulators, which include coactivators and corepressors. Previous studies have revealed that in macrophages, the insulin-sensitizing effect of PPARγ may involve suppression of proinflammatory gene expression by recruiting the corepressor complex that contains corepressors and histone deacetylases (HDACs. Therefore, we investigated whether the corepressor complex is involved in TZD-mediated suppression of TNFα-induced lipolysis in 3T3-L1 adipocytes. Trichostatin A (TSA, a pan HDAC inhibitor (HDACI that inhibits class I and II HDACs, was used to examine the involvement of HDACs in the actions of TZDs. TSA alone increased basal lipolysis and attenuated TZD-mediated suppression of TNFα-induced lipolysis. Increased basal lipolysis may in part result from class I HDAC inhibition because selective class I HDACI treatment had similar results. However, attenuation of TZD-mediated TNFα antagonism may be specific to TSA and related hydroxamate-based HDACI rather than to HDAC inhibition. Consistently, corepressor depletion did not affect TZD-mediated suppression. Interestingly, TSA treatment greatly reduced PPARγ levels in differentiated adipocytes. Finally, extracellular signal-related kinase 1/2 (ERK1/2 mediated TNFα-induced lipolysis, and TZDs suppressed TNFα-induced ERK phosphorylation. We determined that TSA increased basal ERK phosphorylation, and attenuated TZD-mediated suppression of TNFα-induced ERK phosphorylation, consistent with

  14. Regulation of adipocytes lipolysis by n-3 HUFA in grass carp (Ctenopharyngodon idellus) in vitro and in vivo.

    Science.gov (United States)

    Liu, Pin; Li, Chao; Huang, Jiqin; Ji, Hong

    2014-10-01

    N-3 highly unsaturated fatty acids (n-3 HUFA) have been shown to inhibit body fat accumulation in animals. To clarify the mechanism of this fat-lowering effect of n-3 HUFA in grass carp (Ctenopharyngodon idellus), two experiments were conducted. In experiment 1, isolated grass carp mature adipocytes were incubated with docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) at different concentrations for 6 h. The release of glycerol to the medium was detected, and the expression of the lipolysis-related genes was analyzed. In experiment 2, a 95-day feeding trial was conducted with two diets formulated with either lard oil (as control) or fish oil (supplying n-3 HUFA as treatment) as the main lipid source. The glycerol and free fatty acid (FFA) released from the isolated adipocytes of both groups were detected after the feeding period. The expression of select lipolysis-related genes in adipose tissue was also analyzed. The results from experiment 1 showed that the release of glycerol was significantly increased by DHA and EPA (P lipase (ATGL), hormone-sensitive lipase (HSL), tumor necrosis factor α (TNFα) and leptin, was also significantly elevated in the treatment group (P < 0.05). Experiment 2 demonstrated that glycerol and FFA release from the isolated adipocytes were significantly higher in the treatment group compared to the control group (P < 0.05). The expression level of ATGL, HSL, TNFα and leptin in the treatment group was significantly higher than in the control group (P < 0.05). The present results provide novel evidence that n-3 HUFAs could regulate grass carp adipocyte lipolysis in vitro or in vivo, and the effect might be in part associated with their influence on the expression of lipolysis-related genes and lipolysis-related adipokines genes.

  15. Effect of carbohydrate- and protein-rich meals on exercise-induced activation of lipolysis in obese subjects.

    Science.gov (United States)

    Erdmann, J; Tholl, S; Schusdziarra, V

    2010-04-01

    Exercise is an important part of obesity treatment concepts to support fat mobilisation from adipose tissue and also fat oxidation nolich is impaired in obese subjects. In normal weight subjects it is well known that stimulation of plasma insulin levels by a carbohydrate meal can inhibit lipolysis and subsequent fat oxidation. Since obese subjects frequently have elevated basal and postprandial insulin levels the effect of carbohydrate- and protein-rich test meals on exercise-induced activation of lipolysis is of special interest. Twenty obese subjects performed bicycle exercise for 30 min in the fasted state, 30 min after a carbohydrate-or a protein-rich meal, and 120 min after the carbohydrate meal (n=12), respectively, at low intensity. Activation of lipolysis was assessed by plasma glycerol levels. In addition, plasma insulin, glucose, and lactate concentrations were determined. In comparison to the fasted state, the carbohydrate meal suppressed activation of lipolysis. Following the protein meal, exercise led to an attenuated but significant increase of glycerol levels. A similar rise was observed when the carbohydrate meal was ingested 2 h prior to the exercise bout. To improve exercise-induced lipolysis and subsequent fat oxidation during low-intensity exercise obese subjects should not ingest carbohydrates immediately before exercise. Hunger sensations should be satisfied with protein-rich food. When carbohydrates are consumed 2 h prior to exercise its lipolytic effect is comparable to the protein meal. These data are useful in every day dietary counselling and might help to improve weight loss during obesity treatment. Georg Thieme Verlag KG Stuttgart New York.

  16. In vivo nitric oxide suppression of lipolysis in subcutaneous abdominal adipose tissue is greater in obese than lean women.

    Science.gov (United States)

    Hickner, Robert C; Kemeny, Gabor; Clark, Paige D; Galvin, Vaughna B; McIver, Kerry L; Evans, Chris A; Carper, Michael J; Garry, Joseph P

    2012-06-01

    Mounting evidence suggests there is a reduced mobilization of stored fat in obese compared to lean women. It has been suggested that this decreased lipid mobilization may lead to, or perpetuate, the obese state; however, there may be a beneficial effect of reduced lipolysis, either by allowing for a sink of excess fatty acids, or by limiting a potentially harmful rise in interstitial and circulating fatty acid concentration. Nitric oxide (NO) may be responsible for a portion of the reduced in vivo rates of lipolysis in obese women because NO reduces adipose tissue lipolysis and adipose tissue nitric oxide synthase (NOS) mRNA is higher in obese than lean individuals. The purpose of this study was to determine if the inhibition of NOS by L-N(g)-monomethyl-L-arginine (L-NMMA) in the absence and presence of lipolytic stimulation would result in a larger increase in lipolytic rate in obese (OB) than lean (LN) women. Microdialysis probes were inserted into the subcutaneous abdominal adipose tissue of seven obese and six lean women to monitor lipolysis. Dialysate glycerol concentration increased in response to L-NMMA in OB (basal 125 ± 26 µmol/l; L-NMMA 225 ± 35 µmol/l) to a greater extent than in LN (basal 70 ± 18 µmol/l; L-NMMA 84 ± 20 µmol/l) women (P obese and lean could not be explained by differential blood flow responses. It can be concluded that NO suppresses basal lipolysis in obese women to a greater extent than in lean women.

  17. Sexual dimorphic regulation of body weight dynamics and adipose tissue lipolysis.

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    Verena Benz

    Full Text Available BACKGROUND: Successful reduction of body weight (BW is often followed by recidivism to obesity. BW-changes including BW-loss and -regain is associated with marked alterations in energy expenditure (EE and adipose tissue (AT metabolism. Since these processes are sex-specifically controlled, we investigated sexual dimorphisms in metabolic processes during BW-dynamics (gain-loss-regain. RESEARCH DESIGN: Obesity was induced in C57BL/6J male (m and female (f mice by 15 weeks high-fat diet (HFD feeding. Subsequently BW was reduced (-20% by caloric restriction (CR followed by adaptive feeding, and a regain-phase. Measurement of EE, body composition, blood/organ sampling were performed after each feeding period. Lipolysis was analyzed ex-vivo in gonadal AT. RESULTS: Male mice exhibited accelerated BW-gain compared to females (relative BW-gain m:140.5±3.2%; f:103.7±6.5%; p<0.001. In consonance, lean mass-specific EE was significantly higher in females compared to males during BW-gain. Under CR female mice reached their target-BW significantly faster than male mice (m:12.2 days; f:7.6 days; p<0.001 accompanied by a sustained sex-difference in EE. In addition, female mice predominantly downsized gonadal AT whereas the relation between gonadal and total body fat was not altered in males. Accordingly, only females exhibited an increased rate of forskolin-stimulated lipolysis in AT associated with significantly higher glycerol concentrations, lower RER-values, and increased AT expression of adipose triglyceride lipase (ATGL and hormone sensitive lipase (HSL. Analysis of AT lipolysis in estrogen receptor alpha (ERα-deficient mice revealed a reduced lipolytic rate in the absence of ERα exclusively in females. Finally, re-feeding caused BW-regain faster in males than in females. CONCLUSION: The present study shows sex-specific dynamics during BW-gain-loss-regain. Female mice responded to CR with an increase in lipolytic activity, and augmented lipid

  18. Effects of plant enzyme inactivation or sterilization on lipolysis and proteolysis in alfalfa silage.

    Science.gov (United States)

    Ding, W R; Long, R J; Guo, X S

    2013-04-01

    This experiment studied the contribution of plant enzymes and microbial activity on lipolysis and proteolysis in ensiled alfalfa. Before ensiling, the wilted alfalfa was treated with plant enzyme inactivation by autoclaving or with sterilization by γ-ray irradiation. The treated alfalfa was then inoculated with commercial lactic acid bacteria inoculants and ensiled for 40 d. Alfalfa without treatment was ensiled as the control. The content of total fatty acid (FA) after ensiling decreased 43% in the control silage and 28% in the γ-ray-treated silage, but did not change in the autoclave-treated silage. Among the major FA (C16:0, C18:2n-6, C18:3n-3), a considerable increase was observed in proportion of C16:0 in the control silage as compared with fresh alfalfa; conversely, decreases in proportions of C18:2n-6 and C18:3n-3 occurred during ensilage. Silage treated with γ-ray radiation at ensiling had a smaller proportion of C16:0 and greater proportions of C18:2n-6 and C18:3n-3 than control silage. Autoclave treatment further decreased proportions of C16:0 and most of the other FA, and increased C18:2n-6 and C18:3n-3 proportions in comparison with γ-ray treatment. Proportions of C16:0, C18:2n-6, C18:3n-3 and other detected FA (except for the proportion of C15:0) did not differ between fresh forage and autoclave-treated silage. Remarkably, smaller nonprotein nitrogen content was observed in the autoclave-treated silage compared with the γ ray-treated silage or the control silage. These results indicated that an extensive lipolysis occurred during ensiling of alfalfa, and plant enzymes played a major role in lipolysis and proteolysis. Copyright © 2013 American Dairy Science Association. Published by Elsevier Inc. All rights reserved.

  19. Parathyroid hormone induces adipocyte lipolysis via PKA-mediated phosphorylation of hormone-sensitive lipase.

    Science.gov (United States)

    Larsson, Sara; Jones, Helena A; Göransson, Olga; Degerman, Eva; Holm, Cecilia

    2016-03-01

    Parathyroid hormone (PTH) is secreted from the parathyroid glands in response to low plasma calcium levels. Besides its classical actions on bone and kidney, PTH may have other important effects, including metabolic effects, as suggested for instance by increased prevalence of insulin resistance and type 2 diabetes in patients with primary hyperparathyroidism. Moreover, secondary hyperparathyroidism may contribute to the metabolic derangements that characterize states of vitamin D deficiency. PTH has been shown to induce adipose tissue lipolysis, but the details of the lipolytic action of PTH have not been described. Here we used primary mouse adipocytes to show that intact PTH (1-84) as well as the N-terminal fragment (1-37) acutely stimulated lipolysis in a dose-dependent manner, whereas the C-terminal fragment (38-84) was without lipolytic effect. The lipolytic action of PTH was paralleled by phosphorylation of known protein kinase A (PKA) substrates, i.e. hormone-sensitive lipase (HSL) and perilipin. The phosphorylation of HSL in response to PTH occurred at the known PKA sites S563 and S660, but not at the non-PKA site S565. PTH-induced lipolysis, as well as phosphorylation of HSL at S563 and S660, was blocked by both the PKA-inhibitor H89 and the adenylate cyclase inhibitor MDL-12330A, whereas inhibitors of extracellular-regulated kinase (ERK), protein kinase B (PKB), AMP-activated protein kinase (AMPK) and Ca(2+)/calmodulin-dependent protein kinase (CaMK) had little or no effect. Inhibition of phosphodiesterase 4 (PDE4) strongly potentiated the lipolytic action of PTH, whereas inhibition of PDE3 had no effect. Our results show that the lipolytic action of PTH is mediated by the PKA signaling pathway with no or minor contribution of other signaling pathways and, furthermore, that the lipolytic action of PTH is limited by simultaneous activation of PDE4. Knowledge of the signaling pathways involved in the lipolytic action of PTH is important for our

  20. Lipolysis and thermogenesis in adipose tissues as new potential mechanisms for metabolic benefits of dietary fiber.

    Science.gov (United States)

    Han, Shu-Fen; Jiao, Jun; Zhang, Wei; Xu, Jia-Ying; Zhang, Weiguo; Fu, Chun-Ling; Qin, Li-Qiang

    2017-01-01

    Dietary fiber consumption is associated with reduced risk for the development of noncommunicable diseases. The aim of the present study was to evaluate the effects of cereal dietary fiber on the levels of proteins involved in lipolysis and thermogenesis in white adipose tissue (WAT) and brown adipose tissue (BAT) of C57 BL/6 J mice fed a high-fat diet (HFD). Male C57BL/6 J mice were fed normal chow diet (Chow), HFD, HFD plus oat fiber (H-oat), or HFD plus wheat bran fiber (H-wheat) for 24 wk. Body weight and food intake were recorded weekly. Serum adiponectin was assayed by an enzyme-linked immunosorbent assay kit. Western blotting was used to assess the protein expressions of adipose triacylglycerol lipase (ATGL), cAMP protein kinase catalytic subunit (cAMP), protein kinase A (PKA), perilipin A, hormone-sensitive lipase (HSL), uncoupling protein 1 (UCP1), fibroblast growth factor 21 (FGF-21), β3-adrenergic receptor (β3AR), and proliferator-activated receptor gamma coactivator-1 α (PGC-1 α) in the WAT and BAT. At the end of the feeding period, body and adipose tissues weight in both H-oat and H-wheat groups were lower than in the HFD group. Mice in the H-oat and H-wheat groups showed an increasing trend in serum adiponectin level. Compared with the HFD group, cereal dietary fiber increased protein expressions involved in the lipolysis and browning process. Compared with the H-wheat group, H-oat was more effective in protein expressions of PKA, PGC-1 α, and UCP1 of the WAT samples. Compared with the H-oat group, H-wheat was more effective in protein expressions of PKA, ATGL, UCP1, β3AR, and FGF-21 of the BAT samples. Taken together, our results suggested that cereal dietary fiber enhanced adipocyte lipolysis by the cAMP-PKA-HSL pathway and promoted WAT browning by activation of UCP1, and consequently reduced visceral fat mass in response to HFD feeding. Copyright © 2016 Elsevier Inc. All rights reserved.

  1. Kinsenoside-mediated lipolysis through an AMPK-dependent pathway in C3H10T1/2 adipocytes: Roles of AMPK and PPARα in the lipolytic effect of kinsenoside.

    Science.gov (United States)

    Cheng, Kur-Ta; Wang, Yu-Shiou; Chou, Hsiu-Chu; Chang, Chih-Cheng; Lee, Ching-Kuo; Juan, Shu-Hui

    2015-06-01

    Currently, more than one-third of the global population is overweight or obese, which is a risk factor for major causes of death including cardiovascular disease, numerous cancers, and diabetes. Kinsenoside, a major active component of Anoectochilus formosanus exhibits antihyperglycemic, antihyperliposis, and hepatoprotective effects and can be used to prevent and manage obesity. This study examined the catabolic effects of kinsenoside on lipolysis in adipocytes transformed from C3H10T1/2 cells. The lipolytic effect of kinsenoside in C3H10T1/2 adipocytes was evaluated by oil-red O staining and glycerol production. The underlying mechanisms were assessed by Western blots, chromatin immunoprecipitation (IP), Co-IP, EMSA and siRNAs verification. We demonstrated that kinsenoside increased both adipose triglyceride lipase (ATGL)-mediated lipolysis, which was upregulated by AMP-activated protein kinase (AMPK) activation, and the hydrolysis of triglycerides to glycerol and fatty acids that require transportation into mitochondria for further β-oxidation. We also demonstrated that kinsenoside increased the phosphorylation of peroxisome proliferator-activated receptor alpha (PPARα) and CRE-binding protein (CREB), and the protein levels of silent information regulator T1 (SIRT1), peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) and carnitine palmitoyltransferase I (CPT1) through an AMPK-dependent mechanism. SIRT1 deacetylated PGC-1α, facilitating AMPK-mediated PGC-1α phosphorylation and increasing the interaction of PPARα with its coactivator, PGC-1α. This interaction elevated the expression of CPT1, a shuttle for the mitochondrial transport of fatty acids, in kinsenoside-treated cells. In addition, AMPK-phosphorylation-mediated CREB activation caused kinsenoside-mediated PGC-1α upregulation. AMPK activation not only elevated ATGL expression for lipolysis but also induced CPT1 expression for further mitochondrial translocation of fatty

  2. Effects of Acute Hyperglucagonemia on Hepatic and Intestinal Lipoprotein Production and Clearance in Healthy Humans

    Science.gov (United States)

    Xiao, Changting; Pavlic, Mirjana; Szeto, Linda; Patterson, Bruce W.; Lewis, Gary F.

    2011-01-01

    OBJECTIVE The metabolism of hepatic- and intestinally derived lipoproteins is regulated in a complex fashion by nutrients, hormones, and neurologic and other factors. Recent studies in animal models suggest an important role for glucagon acting via the glucagon receptor in regulating hepatic triglyceride (TG) secretion. Here we examined the direct effects of glucagon on regulation of hepatic and intestinal lipoprotein metabolism in humans. RESEARCH DESIGN AND METHODS Eight healthy men underwent two studies each, in random order, 4–6 weeks apart in which de novo lipogenesis, kinetics of larger VLDL1 TG, and kinetics of VLDL1 and smaller VLDL2 apolipoprotein (apo)B100 and B48 were studied using established stable isotope enrichment methods. Subjects were studied in the constant fed state under conditions of a pancreatic clamp (with infusion of somatostatin, insulin, and growth hormone) at either basal glucagon (BG study, 64.5 ± 2.1 pg/mL) or hyperglucagonemia (high glucagon [HG] study, 183.2 ± 5.1 pg/mL). RESULTS There were no significant differences in plasma concentration of VLDL1 or VLDL2 TG, apoB100 or apoB48 between BG and HG studies. There was, however, lower (P lipoprotein metabolism. CONCLUSIONS Glucagon acutely regulates hepatic but not intestinal lipoprotein particle metabolism in humans both by decreasing hepatic lipoprotein particle production as well as by inhibiting particle clearance, with no net effect on particle concentration. PMID:20980459

  3. The Subtle Balance between Lipolysis and Lipogenesis: A Critical Point in Metabolic Homeostasis

    Directory of Open Access Journals (Sweden)

    Chiara Saponaro

    2015-11-01

    Full Text Available Excessive accumulation of lipids can lead to lipotoxicity, cell dysfunction and alteration in metabolic pathways, both in adipose tissue and peripheral organs, like liver, heart, pancreas and muscle. This is now a recognized risk factor for the development of metabolic disorders, such as obesity, diabetes, fatty liver disease (NAFLD, cardiovascular diseases (CVD and hepatocellular carcinoma (HCC. The causes for lipotoxicity are not only a high fat diet but also excessive lipolysis, adipogenesis and adipose tissue insulin resistance. The aims of this review are to investigate the subtle balances that underlie lipolytic, lipogenic and oxidative pathways, to evaluate critical points and the complexities of these processes and to better understand which are the metabolic derangements resulting from their imbalance, such as type 2 diabetes and non alcoholic fatty liver disease.

  4. Effect of training on insulin sensitivity of glucose uptake and lipolysis in human adipose tissue

    DEFF Research Database (Denmark)

    Stallknecht, B; Larsen, J J; Mikines, K J

    2000-01-01

    Training increases insulin sensitivity of both whole body and muscle in humans. To investigate whether training also increases insulin sensitivity of adipose tissue, we performed a three-step hyperinsulinemic, euglycemic clamp in eight endurance-trained (T) and eight sedentary (S) young men...... [insulin infusion rates: 10,000 (step I), 20,000 (step II), and 150,000 (step III) microU x min(-1) x m(-2)]. Glucose and glycerol concentrations were measured in arterial blood and also by microdialysis in interstitial fluid in periumbilical, subcutaneous adipose tissue and in quadriceps femoris muscle......-time: T, 44 +/- 9 min (n = 7); S, 102 +/- 23 min (n = 5); P insulin sensitivity of glucose uptake in subcutaneous adipose tissue and in skeletal muscle. Furthermore, interstitial glycerol data suggest that training also increases insulin sensitivity of lipolysis...

  5. Suppressive Role of PPARγ-Regulated Endothelial Nitric Oxide Synthase in Adipocyte Lipolysis.

    Science.gov (United States)

    Yamada, Yoko; Eto, Masato; Ito, Yuki; Mochizuki, Satoru; Son, Bo-Kyung; Ogawa, Sumito; Iijima, Katsuya; Kaneki, Masao; Kozaki, Koichi; Toba, Kenji; Akishita, Masahiro; Ouchi, Yasuyoshi

    2015-01-01

    Metabolic syndrome causes insulin resistance and is associated with risk factor clustering, thereby increasing the risk of atherosclerosis. Recently, endothelial nitric oxide synthase deficient (eNOS-/-) mice have been reported to show metabolic disorders. Interestingly, eNOS has also been reported to be expressed in non-endothelial cells including adipocytes, but the functions of eNOS in adipocytes remain unclear. The eNOS expression was induced with adipocyte differentiation and inhibition of eNOS/NO enhanced lipolysis in vitro and in vivo. Furthermore, the administration of a high fat diet (HFD) was able to induce non-alcoholic steatohepatitis (NASH) in eNOS-/- mice but not in wild type mice. A PPARγ antagonist increased eNOS expression in adipocytes and suppressed HFD-induced fatty liver changes. eNOS-/- mice induce NASH development, and these findings provide new insights into the therapeutic approach for fatty liver disease and related disorders.

  6. Suppressive Role of PPARγ-Regulated Endothelial Nitric Oxide Synthase in Adipocyte Lipolysis.

    Directory of Open Access Journals (Sweden)

    Yoko Yamada

    Full Text Available Metabolic syndrome causes insulin resistance and is associated with risk factor clustering, thereby increasing the risk of atherosclerosis. Recently, endothelial nitric oxide synthase deficient (eNOS-/- mice have been reported to show metabolic disorders. Interestingly, eNOS has also been reported to be expressed in non-endothelial cells including adipocytes, but the functions of eNOS in adipocytes remain unclear.The eNOS expression was induced with adipocyte differentiation and inhibition of eNOS/NO enhanced lipolysis in vitro and in vivo. Furthermore, the administration of a high fat diet (HFD was able to induce non-alcoholic steatohepatitis (NASH in eNOS-/- mice but not in wild type mice. A PPARγ antagonist increased eNOS expression in adipocytes and suppressed HFD-induced fatty liver changes.eNOS-/- mice induce NASH development, and these findings provide new insights into the therapeutic approach for fatty liver disease and related disorders.

  7. Availability of glucose ingested during muscle exercise performed under acipimox-induced lipolysis blockade.

    Science.gov (United States)

    Gautier, J F; Pirnay, F; Jandrain, B; Lacroix, M; Mosora, F; Scheen, A J; Cathelineau, G; Lefèbvre, P J

    1994-01-01

    This study investigated the percentage of carbohydrate utilization than can be accounted for by glucose ingested during exercise performed after the ingestion of the potent lipolysis inhibitor Acipimox. Six healthy male volunteers exercised for 3 h on a treadmill at about 45% of their maximal oxygen uptake, 75 min after having ingested 250 mg of Acipimox. After 15-min adaptation to exercise, they ingested either glucose dissolved in water, 50 g at time 0 min and 25 g at time 60 and 120 min (glucose, G) or sweetened water (control, C). Naturally labelled [13C]glucose was used to follow the conversion of the ingested glucose to expired-air CO2. Acipimox inhibited lipolysis in a similar manner in both experimental conditions. This was reflected by an almost complete suppression of the exercise-induced increase in plasma free fatty acid and glycerol and by an almost constant rate of lipid oxidation. Total carbohydrate oxidation evaluated by indirect calorimetry, was similar in both experimental conditions [C, 182, (SEM 21); G, 194 (SEM 16) g.3 h-1], as was lipid oxidation [C, 57 (SEM 6); G, 61 (SEM 3) g.3 h-1]. Exogenous glucose oxidation during exercise G, calculated by the changes in 13C:12C ratio of expired air CO2, averaged 66 (SEM 5) g.3 h-1 (19% of the total energy requirement). Consequently, endogenous carbohydrate utilization was significantly smaller after glucose than after placebo ingestion: 128 (SEM 18) versus 182 (SEM 21) g.3 h-1, respectively (P sweet placebo were absent with glucose ingestion.(ABSTRACT TRUNCATED AT 250 WORDS)

  8. Biphasic effects of orexin-A on autonomic nerve activity and lipolysis.

    Science.gov (United States)

    Shen, Jiao; Tanida, Mamoru; Yao, Jia-Fei; Niijima, Akira; Nagai, Katsuya

    2008-10-24

    Previously, we showed that orexin-A, a 33-aa peptide, influences renal sympathetic nerve activity. Because the autonomic nervous system plays an important role in the regulation of lipid metabolism, we investigated the in vivo effects of orexin-A on the sympathetic nerve activity innervating white adipose tissue (WAT-SNA) and lipolysis. We found that intracerebroventricular (icv) administration of orexin-A at doses of 1 microg/rat and 10 ng/rat elevated and suppressed WAT-SNA, respectively. The effect of the high dose of orexin-A (1 microg/rat) was eliminated by pretreatment with diphenhydramine hydrochloride, a histamine H(1) receptor antagonist. In contrast, the effect of the low dose of orexin-A (10 ng/rat) was suppressed by thioperamide maleate salt, a histamine H(3) receptor antagonist. Moreover, icv administration of 1 microg/rat and 10 ng/rat of orexin-A increased and decreased the levels of plasma free fatty acids (FFAs), respectively. The effect of 1 microg/rat of orexin-A on plasma FFA was eliminated by propranolol hydrochloride, a beta-adrenergic receptor blocker, and also by diphenhydramine. The effect of orexin-A at dose of 10 ng/rat disappeared by pretreatment with atropine sulfate, a muscarinic receptor blocker, and thioperamide maleate salt. Our results suggest that high doses of orexin-A may regulate the lipolytic processes in adipose tissue through facilitation of the sympathetic nervous system, which is driven by histamine neurons through the H(1) receptor, and that the beta(3)-receptor may be involved in this enhanced lipolytic response. Low doses of orexin-A, on the other hand, may lower lipolysis by suppressing sympathetic nerve activity via the H(3)-receptor, and the muscarinic receptor may be related to this response.

  9. Sexual Dimorphic Regulation of Body Weight Dynamics and Adipose Tissue Lipolysis

    Science.gov (United States)

    Benz, Verena; Bloch, Mandy; Wardat, Sami; Böhm, Christian; Maurer, Lukas; Mahmoodzadeh, Shokoufeh; Wiedmer, Petra; Spranger, Joachim; Foryst-Ludwig, Anna; Kintscher, Ulrich

    2012-01-01

    Background Successful reduction of body weight (BW) is often followed by recidivism to obesity. BW-changes including BW-loss and -regain is associated with marked alterations in energy expenditure (EE) and adipose tissue (AT) metabolism. Since these processes are sex-specifically controlled, we investigated sexual dimorphisms in metabolic processes during BW-dynamics (gain-loss-regain). Research Design Obesity was induced in C57BL/6J male (m) and female (f) mice by 15 weeks high-fat diet (HFD) feeding. Subsequently BW was reduced (-20%) by caloric restriction (CR) followed by adaptive feeding, and a regain-phase. Measurement of EE, body composition, blood/organ sampling were performed after each feeding period. Lipolysis was analyzed ex-vivo in gonadal AT. Results Male mice exhibited accelerated BW-gain compared to females (relative BW-gain m:140.5±3.2%; f:103.7±6.5%; plipolysis in AT associated with significantly higher glycerol concentrations, lower RER-values, and increased AT expression of adipose triglyceride lipase (ATGL) and hormone sensitive lipase (HSL). Analysis of AT lipolysis in estrogen receptor alpha (ERα)–deficient mice revealed a reduced lipolytic rate in the absence of ERα exclusively in females. Finally, re-feeding caused BW-regain faster in males than in females. Conclusion The present study shows sex-specific dynamics during BW-gain-loss-regain. Female mice responded to CR with an increase in lipolytic activity, and augmented lipid-oxidation leading to more efficient weight loss. These processes likely involve ERα-dependent signaling in AT and sexual dimorphic regulation of genes involved in lipid metabolism. PMID:22662224

  10. Effects of lipoic acid on lipolysis in 3T3-L1 adipocytes[S

    Science.gov (United States)

    Fernández-Galilea, Marta; Pérez-Matute, Patricia; Prieto-Hontoria, Pedro L; Martinez, J Alfredo; Moreno-Aliaga, Maria J

    2012-01-01

    Lipoic acid (LA) is a naturally occurring compound with beneficial effects on obesity. The aim of this study was to evaluate its effects on lipolysis in 3T3-L1 adipocytes and the mechanisms involved. Our results revealed that LA induced a dose- and time-dependent lipolytic action, which was reversed by pretreatment with the c-Jun N-terminal kinase inhibitor SP600125, the PKA inhibitor H89, and the AMP-activated protein kinase activator AICAR. In contrast, the PI3K/Akt inhibitor LY294002 and the PDE3B antagonist cilostamide enhanced LA-induced lipolysis. LA treatment for 1 h did not modify total protein content of hormone-sensitive lipase (HSL) but significantly increased the phosphorylation of HSL at Ser563 and at Ser660, which was reversed by H89. LA treatment also induced a marked increase in PKA-mediated perilipin phosphorylation. LA did not significantly modify the protein levels of adipose triglyceride lipase or its activator comparative gene identification 58 (CGI-58) and inhibitor G(0)/G(1) switch gene 2 (G0S2). Furthermore, LA caused a significant inhibition of adipose-specific phospholipase A2 (AdPLA) protein and mRNA levels in parallel with a decrease in the amount of prostaglandin E2 released and an increase in cAMP content. Together, these data suggest that the lipolytic actions of LA are mainly mediated by phosphorylation of HSL through cAMP-mediated activation of protein kinase A probably through the inhibition of AdPLA and prostaglandin E2. PMID:22941773

  11. Cardiotrophin-1 stimulates lipolysis through the regulation of main adipose tissue lipases[S

    Science.gov (United States)

    López-Yoldi, Miguel; Fernández-Galilea, Marta; Laiglesia, Laura M.; Larequi, Eduardo; Prieto, Jesús; Martínez, J. Alfredo; Bustos, Matilde; Moreno-Aliaga, Maria J.

    2014-01-01

    Cardiotrophin-1 (CT-1) is a cytokine with antiobesity properties and with a role in lipid metabolism regulation and adipose tissue function. The aim of this study was to analyze the molecular mechanisms involved in the lipolytic actions of CT-1 in adipocytes. Recombinant CT-1 (rCT-1) effects on the main proteins and signaling pathways involved in the regulation of lipolysis were evaluated in 3T3-L1 adipocytes and in mice. rCT-1 treatment stimulated basal glycerol release in a concentration- and time-dependent manner in 3T3-L1 adipocytes. rCT-1 (20 ng/ml for 24 h) raised cAMP levels, and in parallel increased protein kinase (PK)A-mediated phosphorylation of perilipin and hormone sensitive lipase (HSL) at Ser660. siRNA knock-down of HSL or PKA, as well as pretreatment with the PKA inhibitor H89, blunted the CT-1-induced lipolysis, suggesting that the lipolytic action of CT-1 in adipocytes is mainly mediated by activation of HSL through the PKA pathway. In ob/ob mice, acute rCT-1 treatment also promoted PKA-mediated phosphorylation of perilipin and HSL at Ser660 and Ser563, and increased adipose triglyceride lipase (desnutrin) content in adipose tissue. These results showed that the ability of CT-1 to regulate the activity of the main lipases underlies the lipolytic action of this cytokine in vitro and in vivo, and could contribute to CT-1 antiobesity effects. PMID:25351614

  12. Tofogliflozin Improves Insulin Resistance in Skeletal Muscle and Accelerates Lipolysis in Adipose Tissue in Male Mice.

    Science.gov (United States)

    Obata, Atsushi; Kubota, Naoto; Kubota, Tetsuya; Iwamoto, Masahiko; Sato, Hiroyuki; Sakurai, Yoshitaka; Takamoto, Iseki; Katsuyama, Hisayuki; Suzuki, Yoshiyuki; Fukazawa, Masanori; Ikeda, Sachiya; Iwayama, Kaito; Tokuyama, Kumpei; Ueki, Kohjiro; Kadowaki, Takashi

    2016-03-01

    Sodium glucose cotransporter 2 inhibitors have attracted attention as they exert antidiabetic and antiobesity effects. In this study, we investigated the effects of tofogliflozin on glucose homeostasis and its metabolic consequences and clarified the underlying molecular mechanisms. C57BL/6 mice were fed normal chow containing tofogliflozin (0.005%) for 20 weeks or a high-fat diet containing tofogliflozin (0.005%) for 8 weeks ad libitum. In addition, the animals were pair-fed in relation to controls to exclude the influence of increased food intake. Tofogliflozin reduced the body weight gain, mainly because of fat mass reduction associated with a diminished adipocyte size. Glucose tolerance and insulin sensitivity were ameliorated. The serum levels of nonesterified fatty acid and ketone bodies were increased and the respiratory quotient was decreased in the tofogliflozin-treated mice, suggesting the acceleration of lipolysis in the white adipose tissue and hepatic β-oxidation. In fact, the phosphorylation of hormone-sensitive lipase and the adipose triglyceride lipase protein levels in the white adipose tissue as well as the gene expressions related to β-oxidation, such as Cpt1α in the liver, were significantly increased. The hepatic triglyceride contents and the expression levels of lipogenic genes were decreased. Pair-fed mice exhibited almost the same results as mice fed an high-fat diet ad libitum. Moreover, a hyperinsulinemic-euglycemic clamp revealed that tofogliflozin improved insulin resistance by increasing glucose uptake, especially in the skeletal muscle, in pair-fed mice. Taken together, these results suggest tofogliflozin ameliorates insulin resistance and obesity by increasing glucose uptake in skeletal muscle and lipolysis in adipose tissue.

  13. Prostaglandin E2 receptor EP3 regulates both adipogenesis and lipolysis in mouse white adipose tissue.

    Science.gov (United States)

    Xu, Hu; Fu, Jia-Lin; Miao, Yi-Fei; Wang, Chun-Jiong; Han, Qi-Fei; Li, Sha; Huang, Shi-Zheng; Du, Sheng-Nan; Qiu, Yu-Xiang; Yang, Ji-Chun; Gustafsson, Jan-Åke; Breyer, Richard M; Zheng, Feng; Wang, Nan-Ping; Zhang, Xiao-Yan; Guan, You-Fei

    2016-12-01

    Among the four prostaglandin E2 receptors, EP3 receptor is the one most abundantly expressed in white adipose tissue (WAT). The mouse EP3 gene gives rise to three isoforms, namely EP3α, EP3β, and EP3γ, which differ only at their C-terminal tails. To date, functions of EP3 receptor and its isoforms in WAT remain incompletely characterized. In this study, we found that the expression of all EP3 isoforms were downregulated in WAT of both db/db and high-fat diet-induced obese mice. Genetic ablation of three EP3 receptor isoforms (EP3(-/-) mice) or EP3α and EP3γ isoforms with EP3β intact (EP3β mice) led to an obese phenotype with increased food intake, decreased motor activity, reduced insulin sensitivity, and elevated serum triglycerides. Since the differentiation of preadipocytes and mouse embryonic fibroblasts to adipocytes was markedly facilitated by either pharmacological blockade or genetic deletion/inhibition of EP3 receptor via the cAMP/PKA/PPARγ pathway, increased adipogenesis may contribute to obesity in EP3(-/-) and EP3β mice. Moreover, both EP3(-/-) and EP3β mice had increased lipolysis in WAT mainly due to the activated cAMP/PKA/hormone-sensitive lipase pathway. Taken together, our findings suggest that EP3 receptor and its α and γ isoforms are involved in both adipogenesis and lipolysis and influence food intake, serum lipid levels, and insulin sensitivity. © The Author (2016). Published by Oxford University Press on behalf of Journal of Molecular Cell Biology, IBCB, SIBS, CAS. All rights reserved.

  14. Artificial sweeteners stimulate adipogenesis and suppress lipolysis independently of sweet taste receptors.

    Science.gov (United States)

    Simon, Becky R; Parlee, Sebastian D; Learman, Brian S; Mori, Hiroyuki; Scheller, Erica L; Cawthorn, William P; Ning, Xiaomin; Gallagher, Katherine; Tyrberg, Björn; Assadi-Porter, Fariba M; Evans, Charles R; MacDougald, Ormond A

    2013-11-08

    G protein-coupled receptors mediate responses to a myriad of ligands, some of which regulate adipocyte differentiation and metabolism. The sweet taste receptors T1R2 and T1R3 are G protein-coupled receptors that function as carbohydrate sensors in taste buds, gut, and pancreas. Here we report that sweet taste receptors T1R2 and T1R3 are expressed throughout adipogenesis and in adipose tissues. Treatment of mouse and human precursor cells with artificial sweeteners, saccharin and acesulfame potassium, enhanced adipogenesis. Saccharin treatment of 3T3-L1 cells and primary mesenchymal stem cells rapidly stimulated phosphorylation of Akt and downstream targets with functions in adipogenesis such as cAMP-response element-binding protein and FOXO1; however, increased expression of peroxisome proliferator-activated receptor γ and CCAAT/enhancer-binding protein α was not observed until relatively late in differentiation. Saccharin-stimulated Akt phosphorylation at Thr-308 occurred within 5 min, was phosphatidylinositol 3-kinase-dependent, and occurred in the presence of high concentrations of insulin and dexamethasone; phosphorylation of Ser-473 occurred more gradually. Surprisingly, neither saccharin-stimulated adipogenesis nor Thr-308 phosphorylation was dependent on expression of T1R2 and/or T1R3, although Ser-473 phosphorylation was impaired in T1R2/T1R3 double knock-out precursors. In mature adipocytes, artificial sweetener treatment suppressed lipolysis even in the presence of forskolin, and lipolytic responses were correlated with phosphorylation of hormone-sensitive lipase. Suppression of lipolysis by saccharin in adipocytes was also independent of T1R2 and T1R3. These results suggest that some artificial sweeteners have previously uncharacterized metabolic effects on adipocyte differentiation and metabolism and that effects of artificial sweeteners on adipose tissue biology may be largely independent of the classical sweet taste receptors, T1R2 and T1R3.

  15. Acidity and lipolysis by group V secreted phospholipase A(2) strongly increase the binding of apoB-100-containing lipoproteins to human aortic proteoglycans.

    Science.gov (United States)

    Lähdesmäki, Katariina; Öörni, Katariina; Alanne-Kinnunen, Mervi; Jauhiainen, Matti; Hurt-Camejo, Eva; Kovanen, Petri T

    2012-02-01

    Local acidic areas characterize diffuse intimal thickening (DIT) and advanced atherosclerotic lesions. The role of acidity in the modification and extra- and intracellular accumulation of triglyceride-rich VLDL and IDL particles has not been studied before. Here, we examined the effects of acidic pH on the activity of recombinant human group V secreted phospholipase A(2) (sPLA(2)-V) toward small VLDL (sVLDL), IDL, and LDL, on the binding of these apoB-100-containing lipoproteins to human aortic proteoglycans, and on their uptake by human monocyte-derived macrophages. At acidic pH, the ability of sPLA(2)-V to lipolyze the apoB-100-containing lipoproteins was moderately, but significantly, increased while binding of the lipoproteins to proteoglycans increased >60-fold and sPLA(2)-V-modification further doubled the binding. Moreover, acidic pH more than doubled macrophage uptake of soluble complexes of sPLA(2)-V-LDL with aortic proteoglycans. Proteoglycan-affinity chromatography at pH 7.5 and 5.5 revealed that sVLDL, IDL, and LDL consisted of populations with different proteoglycan-binding affinities, and, surprisingly, the sVLDL fractions with the highest proteoglycan-affinity contained only low amounts of apolipoproteins E and C-III. Our results suggest that in atherosclerotic lesions with acidic extracellular pH, sPLA(2)-V is able to lipolyze sVLDL, IDL, and LDL, and increase their binding to proteoglycans. This is likely to provoke extracellular accumulation of lipids derived from these atherogenic lipoprotein particles and to increase the progression of the atherosclerotic lesions.

  16. The neuropeptide TLQP-21 opposes obesity via C3aR1-mediated enhancement of adrenergic-induced lipolysis

    Directory of Open Access Journals (Sweden)

    Cheryl Cero

    2017-01-01

    Conclusions: In conclusion, our data identify an alternative pathway modulating lipolysis that could be targeted to diminish fat mass in obesity without the side effects typically observed when using potent pro-lipolytic molecules.

  17. Inhibition of miR-33a/b in non-human primates raises plasma HDL and lowers VLDL triglycerides.

    Science.gov (United States)

    Rayner, Katey J; Esau, Christine C; Hussain, Farah N; McDaniel, Allison L; Marshall, Stephanie M; van Gils, Janine M; Ray, Tathagat D; Sheedy, Frederick J; Goedeke, Leigh; Liu, Xueqing; Khatsenko, Oleg G; Kaimal, Vivek; Lees, Cynthia J; Fernandez-Hernando, Carlos; Fisher, Edward A; Temel, Ryan E; Moore, Kathryn J

    2011-10-19

    Cardiovascular disease remains the leading cause of mortality in westernized countries, despite optimum medical therapy to reduce the levels of low-density lipoprotein (LDL)-associated cholesterol. The pursuit of novel therapies to target the residual risk has focused on raising the levels of high-density lipoprotein (HDL)-associated cholesterol in order to exploit its atheroprotective effects. MicroRNAs (miRNAs) have emerged as important post-transcriptional regulators of lipid metabolism and are thus a new class of target for therapeutic intervention. MicroRNA-33a and microRNA-33b (miR-33a/b) are intronic miRNAs whose encoding regions are embedded in the sterol-response-element-binding protein genes SREBF2 and SREBF1 (refs 3-5), respectively. These miRNAs repress expression of the cholesterol transporter ABCA1, which is a key regulator of HDL biogenesis. Recent studies in mice suggest that antagonizing miR-33a may be an effective strategy for raising plasma HDL levels and providing protection against atherosclerosis; however, extrapolating these findings to humans is complicated by the fact that mice lack miR-33b, which is present only in the SREBF1 gene of medium and large mammals. Here we show in African green monkeys that systemic delivery of an anti-miRNA oligonucleotide that targets both miR-33a and miR-33b increased hepatic expression of ABCA1 and induced a sustained increase in plasma HDL levels over 12 weeks. Notably, miR-33 antagonism in this non-human primate model also increased the expression of miR-33 target genes involved in fatty acid oxidation (CROT, CPT1A, HADHB and PRKAA1) and reduced the expression of genes involved in fatty acid synthesis (SREBF1, FASN, ACLY and ACACA), resulting in a marked suppression of the plasma levels of very-low-density lipoprotein (VLDL)-associated triglycerides, a finding that has not previously been observed in mice. These data establish, in a model that is highly relevant to humans, that pharmacological inhibition

  18. Inhibition of miR-33a/b in non-human primates raises plasma HDL and reduces VLDL triglycerides

    Science.gov (United States)

    Rayner, Katey J.; Esau, Christine C.; Hussain, Farah N.; McDaniel, Allison L.; Marshall, Stephanie M.; van Gils, Janine M.; Ray, Tathagat D.; Sheedy, Frederick J.; Goedeke, Leigh; Liu, Xueqing; Khatsenko, Oleg G.; Kaimal, Vivek; Lees, Cynthia J.; Fernandez-Hernando, Carlos; Fisher, Edward A.; Temel, Ryan E.; Moore, Kathryn J.

    2011-01-01

    Cardiovascular disease (CVD) remains the leading cause of mortality in westernized countries, despite optimum medical therapy to lower LDL cholesterol. The pursuit of novel therapies to target this residual risk has focused on raising levels of HDL cholesterol in order to exploit its atheroprotective effects1. MicroRNAs have emerged as important post-transcriptional regulators of lipid metabolism, and are thus a new class of targets for therapeutic intervention2. MicroRNA-33a and b (miR-33a/b) are intronic microRNAs embedded in the sterol response element binding protein genes SREBF2 and SREBF13–5, respectively, that repress expression of the cholesterol transporter ABCA1, a key regulator of HDL biogenesis. Recent studies in mice suggest that antagonizing miR-33a may be an effective strategy for raising plasma HDL3–5 and protecting from atherosclerosis6, however extrapolation of these findings to humans is complicated by the fact that mice lack miR-33b which is present only in the SREBF1 gene of higher mammals. Here we show in African green monkeys that systemic delivery of an anti-miR oligonucleotide that targets both miR-33a and miR-33b increases hepatic expression of ABCA1 and induces a sustained increase in plasma HDL over 12 weeks. Notably, miR-33 antagonism in this non-human primate model also increased the expression of miR-33 target genes involved in the oxidation of fatty acids (CROT, CPT1A, HADHB, PRKAA1) and reduced genes involved in fatty acid synthesis (SREBF1, FASN, ACLY, ACACA), resulting in a marked suppression of plasma VLDL triglyceride levels, a finding not previously observed in mice. These data establish, in a model highly relevant to humans, that pharmacological inhibition of miR-33a and b is a promising therapeutic strategy to raise plasma HDL and lower VLDL triglycerides for the treatment of dyslipidemias that increase cardiovascular disease risk. PMID:22012398

  19. Fat-specific Protein 27 (FSP27) Interacts with Adipose Triglyceride Lipase (ATGL) to Regulate Lipolysis and Insulin Sensitivity in Human Adipocytes*

    Science.gov (United States)

    Grahn, Tan Hooi Min; Kaur, Rajween; Yin, Jun; Schweiger, Martina; Sharma, Vishva Mitra; Lee, Mi-Jeong; Ido, Yasuo; Smas, Cynthia M.; Zechner, Rudolf; Lass, Achim; Puri, Vishwajeet

    2014-01-01

    In adipocytes, lipolysis is a highly regulated process involving hormonal signals, lipid droplet-associated proteins, and lipases. The discovery of new lipid droplet-associated proteins added complexity to the current model of lipolysis. In this study, we used cultured human adipocytes to demonstrate that fat-specific protein 27 (FSP27), an abundantly expressed protein in adipocytes, regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase (ATGL, also called desnutrin or PNPLA2). We identified a core domain of FSP27, amino acids 120–220, that interacts with ATGL to inhibit its lipolytic function and promote triglyceride storage. We also defined the role of FSP27 in free fatty acid-induced insulin resistance in adipocytes. FSP27 depletion in human adipocytes increased lipolysis and inhibited insulin signaling by decreasing AKT phosphorylation. However, reducing lipolysis by either depletion of ATGL or expression of exogenous full-length FSP27 or amino acids 120–220 protected human adipocytes against the adverse effects of free fatty acids on insulin signaling. In embryonic fibroblasts derived from ATGL KO mice, exogenous free fatty acids did not affect insulin sensitivity. Our results demonstrate a crucial role for FSP27-ATGL interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes. PMID:24627478

  20. Fat-specific protein 27 (FSP27) interacts with adipose triglyceride lipase (ATGL) to regulate lipolysis and insulin sensitivity in human adipocytes.

    Science.gov (United States)

    Grahn, Tan Hooi Min; Kaur, Rajween; Yin, Jun; Schweiger, Martina; Sharma, Vishva Mitra; Lee, Mi-Jeong; Ido, Yasuo; Smas, Cynthia M; Zechner, Rudolf; Lass, Achim; Puri, Vishwajeet

    2014-04-25

    In adipocytes, lipolysis is a highly regulated process involving hormonal signals, lipid droplet-associated proteins, and lipases. The discovery of new lipid droplet-associated proteins added complexity to the current model of lipolysis. In this study, we used cultured human adipocytes to demonstrate that fat-specific protein 27 (FSP27), an abundantly expressed protein in adipocytes, regulates both basal and stimulated lipolysis by interacting with adipose triglyceride lipase (ATGL, also called desnutrin or PNPLA2). We identified a core domain of FSP27, amino acids 120-220, that interacts with ATGL to inhibit its lipolytic function and promote triglyceride storage. We also defined the role of FSP27 in free fatty acid-induced insulin resistance in adipocytes. FSP27 depletion in human adipocytes increased lipolysis and inhibited insulin signaling by decreasing AKT phosphorylation. However, reducing lipolysis by either depletion of ATGL or expression of exogenous full-length FSP27 or amino acids 120-220 protected human adipocytes against the adverse effects of free fatty acids on insulin signaling. In embryonic fibroblasts derived from ATGL KO mice, exogenous free fatty acids did not affect insulin sensitivity. Our results demonstrate a crucial role for FSP27-ATGL interactions in regulating lipolysis, triglyceride accumulation, and insulin signaling in human adipocytes.

  1. Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity

    Science.gov (United States)

    Ding, Lei; Zhang, Feng; Zhao, Ming-Xia; Ren, Xing-Sheng; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-01-01

    Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity. PMID:27694818

  2. Reduced lipolysis response to adipose afferent reflex involved in impaired activation of adrenoceptor-cAMP-PKA-hormone sensitive lipase pathway in obesity.

    Science.gov (United States)

    Ding, Lei; Zhang, Feng; Zhao, Ming-Xia; Ren, Xing-Sheng; Chen, Qi; Li, Yue-Hua; Kang, Yu-Ming; Zhu, Guo-Qing

    2016-10-03

    Chemical stimulation of white adipose tissue (WAT) causes adipose afferent reflex (AAR) and sympathetic activation. This study is to investigate the effects of AAR on lipolysis and the mechanisms of attenuated lipolysis response to enhanced AAR in obesity. Obesity was caused by high-fat diet for 12 weeks in rats. AAR was induced by injection of capsaicin into inguinal WAT or electrical stimulation of epididymal WAT afferent nerve. AAR caused sympathetic activation, which was enhanced in obesity rats. AAR increased cAMP levels and PKA activity, promoted hormone sensitive lipase (HSL) and perilipin phosphorylation, and increased lipolysis in WAT, which were attenuated in obesity rats. PKA activity, cAMP, perilipin and β-adrenoceptor levels were reduced, while HSL was upregulated in adipocytes from obesity rats. In primary adipocytes, isoproterenol increased cAMP levels and PKA activity, promoted HSL and perilipin phosphorylation, and increased lipolysis, which were attenuated in obesity rats. The attenuated effects of isoproterenol in adipocytes from obesity rats were prevented by a cAMP analogue dbcAMP. The results indicate that reduced lipolysis response to enhanced AAR in obesity is attributed to the impaired activation of β-adrenoceptor-cAMP-PKA-HSL pathway. Increased cAMP level in adipocytes rectifies the attenuated lipolysis in obesity.

  3. Fatty acids from fat cell lipolysis do not activate an inflammatory response but are stored as triacylglycerols in adipose tissue macrophages.

    Science.gov (United States)

    Caspar-Bauguil, Sylvie; Kolditz, Catherine-Ines; Lefort, Corinne; Vila, Isabelle; Mouisel, Etienne; Beuzelin, Diane; Tavernier, Geneviève; Marques, Marie-Adeline; Zakaroff-Girard, Alexia; Pecher, Christiane; Houssier, Marianne; Mir, Lucile; Nicolas, Sarah; Moro, Cédric; Langin, Dominique

    2015-11-01

    Activation of macrophages by fatty acids (FAs) is a potential mechanism linking obesity to adipose tissue (AT) inflammation and insulin resistance. Here, we investigated the effects of FAs released during adipocyte lipolysis on AT macrophages (ATMs). Human THP-1 macrophages were treated with media from human multipotent adipose-derived stem (hMADS) adipocytes stimulated with lipolytic drugs. Macrophages were also treated with mixtures of FAs and an inhibitor of Toll-like receptor 4, since this receptor is activated by saturated FAs. Levels of mRNA and the secretion of inflammation-related molecules were measured in macrophages. FA composition was determined in adipocytes, conditioned media and macrophages. The effect of chronic inhibition or acute activation of fat cell lipolysis on ATM response was investigated in vivo in mice. Whereas palmitic acid alone activates THP-1, conditioned media from hMADS adipocyte lipolysis had no effect on IL, chemokine and cytokine gene expression, and secretion by macrophages. Mixtures of FAs representing de novo lipogenesis or habitual dietary conditions also had no effect. FAs derived from adipocyte lipolysis were taken up by macrophages and stored as triacylglycerol droplets. In vivo, chronic treatment with an antilipolytic drug did not modify gene expression and number of ATMs in mice with intact or defective Tlr4. Stimulation of adipocyte lipolysis increased storage of neutral lipids by macrophages without change in number and phenotype. Our data suggest that adipocyte lipolysis does not activate inflammatory pathways in ATMs, which instead may act as scavengers of FAs.

  4. Impact of pasteurization of human milk on preterm newborn in vitro digestion: Gastrointestinal disintegration, lipolysis and proteolysis.

    Science.gov (United States)

    de Oliveira, Samira C; Bourlieu, Claire; Ménard, Olivia; Bellanger, Amandine; Henry, Gwénaële; Rousseau, Florence; Dirson, Emelyne; Carrière, Frédéric; Dupont, Didier; Deglaire, Amélie

    2016-11-15

    Human milk feeding is an important recommendation for preterm newborns considering their vulnerability and digestive immaturity. Holder pasteurization (62.5°C, 30min) applied in milk banks modifies its biological quality and its microstructure. We investigated the impact of pasteurization of preterm human milk on its gastrointestinal kinetics of lipolysis, proteolysis and structural disintegration. An in vitro dynamic system was set up to simulate the gastrointestinal digestion of preterm newborns. A pool of preterm human milk was digested as raw or after Holder pasteurization. Pasteurization impacted the microstructure of undigested human milk, its gastrointestinal disintegration and tended to limit the intestinal lipolysis. Furthermore, the gastrointestinal bioaccessibility of some fatty acids was decreased by pasteurization, while the intestinal bioaccessibility of some amino acids was selectively modulated. The impact of pasteurization on the digestion of human milk may have nutritional relevance in vivo and potentially modulates preterm development and growth. Copyright © 2016 Elsevier Ltd. All rights reserved.

  5. A common haplotype in the G-protein-coupled receptor gene GPR74 is associated with leanness and increased lipolysis

    DEFF Research Database (Denmark)

    Dahlman, Ingrid; Dicker, Andrea; Jiao, Hong

    2007-01-01

    0.36; P=.036) among those selected for obese or lean phenotypes. The ATAG haplotype was associated with increased adipocyte lipid mobilization (lipolysis) in vivo and in vitro. In human fat cells, GPR74 receptor stimulation and inhibition caused a significant and marked decrease and increase......, respectively, of lipolysis, which could be linked to catecholamine stimulation of adipocytes through beta -adrenergic receptors. These findings suggest that a common haplotype in the GPR74 gene protects against obesity, which, at least in part, is caused by a relief of inhibition of lipid mobilization from...... with protection against obesity in two samples selected for obese and lean phenotypes (odds ratio for obesity 0.48 and 0.62; nominal P=.0014 and .014; n=1,013 and 1,423, respectively). In a population-based sample, it was associated with lower waist (P=.02) among 3,937 men and with obesity protection (odds ratio...

  6. Solid lipid particles for oral delivery of peptide and protein drugs I - Elucidating the release mechanism of lysozyme during lipolysis

    DEFF Research Database (Denmark)

    Christophersen, Philip Carsten B; Zhang, L.; Yang, M

    2013-01-01

    The mechanism of protein release from solid lipid particles was investigated by a new lipolysis model in a biorelevant medium containing both bile salts and phospholipids. Lysozyme, a model protein, was formulated into solid lipid particles using four different types of lipids, two triglycerides...... with different chain-length of fatty acyl groups i.e. trimyristin (TG14) and tristearin (TG18), and two lipid blends dominated by diglycerides and monoglycerides, respectively. The release of lysozyme from the solid lipid particles and the lipid hydrolysis process were assessed in the lipolysis model, while...... the drug release mechanism from solid lipid particles and can potentially be used in rational selection of lipid excipients for oral delivery of peptide/protein drugs....

  7. Lipolysis and apoptosis of adipocytes induced by neuropeptide Y—Y5 receptor antisense oligodeoxynucleotides in obese rats

    Institute of Scientific and Technical Information of China (English)

    GONGHai-Xia; GUOXi-Rong; FEILi; GUOMei; LIUQian-Qi; CHENRong-Hua

    2003-01-01

    AIM:To investigate the influence of central administration of neuropeptide Y-Y5 receptor antisense oligodeoxynucleotides(ODN) on the body weight and fat pads of high-energy diet-induced obese rats, and the effects on white adipocyte lipolysis and apoptosis. METHODS: Y5 receptor antisense, sense, mismatched oligodeoxynucleotides (ODN) or vehicle were intracerebroventricularly injected, and average adipocyte area was calculated. DNA ladders were measured to evaluate adipocyte apoptosis, and RT-PCR was used to analyze the expression of bcl-2 and bax gene. RESULTS: (1) Central administration of Y5 receptor antisense ODN significantly decreased body weight, fat pads, and average adipocyte area. (2) DNA fragmentation was presented after electrophoresis at both epididymal and retroperitoneal adipose tissue. (3) The expression of bcl-2 gene was downregulated, while the expression of bax was upregulated. CONCLUSION:Lipolysis and adipocyte apoptosis may be important reasons for Y5 receptor antisense therapy.

  8. Contraction-induced lipolysis is not impaired by inhibition of hormone-sensitive lipase in skeletal muscle

    DEFF Research Database (Denmark)

    Alsted, Thomas Junker; Ploug, Thorkil; Prats Gavalda, Clara

    2013-01-01

    In skeletal muscle hormone-sensitive lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro lipase activity data, which may not reflect the in vivo lipolytic...... activity. We investigated lipolysis of IMTG in soleus muscles electrically-stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL-KO mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibers....... To circumvent the problem with this contamination we analyzed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (p...

  9. Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy

    Directory of Open Access Journals (Sweden)

    Fuyang Zhang

    2016-11-01

    Full Text Available The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD + BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR, inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA in the HFD + BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte.

  10. Branched Chain Amino Acids Cause Liver Injury in Obese/Diabetic Mice by Promoting Adipocyte Lipolysis and Inhibiting Hepatic Autophagy.

    Science.gov (United States)

    Zhang, Fuyang; Zhao, Shihao; Yan, Wenjun; Xia, Yunlong; Chen, Xiyao; Wang, Wei; Zhang, Jinglong; Gao, Chao; Peng, Cheng; Yan, Feng; Zhao, Huishou; Lian, Kun; Lee, Yan; Zhang, Ling; Lau, Wayne Bond; Ma, Xinliang; Tao, Ling

    2016-11-01

    The Western meat-rich diet is both high in protein and fat. Although the hazardous effect of a high fat diet (HFD) upon liver structure and function is well recognized, whether the co-presence of high protein intake contributes to, or protects against, HF-induced hepatic injury remains unclear. Increased intake of branched chain amino acids (BCAA, essential amino acids compromising 20% of total protein intake) reduces body weight. However, elevated circulating BCAA is associated with non-alcoholic fatty liver disease and injury. The mechanisms responsible for this quandary remain unknown; the role of BCAA in HF-induced liver injury is unclear. Utilizing HFD or HFD+BCAA models, we demonstrated BCAA supplementation attenuated HFD-induced weight gain, decreased fat mass, activated mammalian target of rapamycin (mTOR), inhibited hepatic lipogenic enzymes, and reduced hepatic triglyceride content. However, BCAA caused significant hepatic damage in HFD mice, evidenced by exacerbated hepatic oxidative stress, increased hepatic apoptosis, and elevated circulation hepatic enzymes. Compared to solely HFD-fed animals, plasma levels of free fatty acids (FFA) in the HFD+BCAA group are significantly further increased, due largely to AMPKα2-mediated adipocyte lipolysis. Lipolysis inhibition normalized plasma FFA levels, and improved insulin sensitivity. Surprisingly, blocking lipolysis failed to abolish BCAA-induced liver injury. Mechanistically, hepatic mTOR activation by BCAA inhibited lipid-induced hepatic autophagy, increased hepatic apoptosis, blocked hepatic FFA/triglyceride conversion, and increased hepatocyte susceptibility to FFA-mediated lipotoxicity. These data demonstrated that BCAA reduces HFD-induced body weight, at the expense of abnormal lipolysis and hyperlipidemia, causing hepatic lipotoxicity. Furthermore, BCAA directly exacerbate hepatic lipotoxicity by reducing lipogenesis and inhibiting autophagy in the hepatocyte.

  11. Mechanism for desensitization of beta-adrenergic receptor-stimulated lipolysis in adipocytes from rats harboring pheochromocytoma.

    Science.gov (United States)

    Prokocimer, P G; Maze, M; Vickery, R G; Hoffman, B B

    1988-07-01

    Prolonged stimulation of beta-adrenergic receptors with catecholamines leads to desensitization of their ability to activate cAMP accumulation. However, little is known about the relationship between these changes and possible alterations in physiological responses. We have used isolated adipocytes prepared from NEDH rats harboring pheochromocytomas, a norepinephrine-secreting tumor, to address this question. As expected, there was a decrease in the ability of isoproterenol to maximally activate cAMP accumulation in adipocytes from rat harboring pheochromocytoma [323 +/- 107 vs. 707 +/- 145 pmol/10(5) cells.min (mean +/- SD) in controls]. This change was associated with an increase in the EC50 of isoproterenol for activation of cAMP-dependent protein kinase (5.8 X 10(-8) vs. 2.4 X 10(-8) M in controls) and a decrease in maximal activation of the kinase (38 +/- 16% vs. 77 +/- 14% in controls). For lipolysis there was a loss in sensitivity to isoproterenol but no change in maximal lipolytic rate in the adipocytes from rats harboring pheochromocytoma. For both groups there was a similar relationship between kinase activation and lipolysis; maximal lipolysis had already occurred for protein kinase-A activity ratios less than 30%. Therefore, the blunted cAMP response in adipocytes from rats harboring pheochromocytoma did not impair the maximal lipolytic rate. These results demonstrate that adipocytes can efficiently maintain maximal lipolysis in a desensitized state because of considerable reserve in the biochemical cascade leading to the lipolytic response. In addition, our findings demonstrate that there are no regulatory changes induced by prolonged exposure to catecholamines that are distal to cAMP accumulation.

  12. Effect of germinated brown rice extracts on pancreatic lipase, adipogenesis and lipolysis in 3T3-L1 adipocytes.

    Science.gov (United States)

    Lim, See Meng; Goh, Yong Meng; Kuan, Wen Bin; Loh, Su Peng

    2014-11-03

    This study investigated anti-obesity effects of seven different solvent (n-hexane, toluene, dicholoromethane, ethyl acetate, absolute methanol, 80% methanol and deionized water) extracts of germinated brown rice (GBR) on pancreatic lipase activity, adipogenesis and lipolysis in 3T3-L1 adipocytes. GBR were extracted separately by employing different solvents with ultrasound-assisted. Pancreatic lipase activity was determined spectrophotometrically by measuring the hydrolysis of p-nitrophenyl butyrate (p-NPB) to p-nitrophenol at 405 nm. Adipogenesis and lipolysis were assayed in fully differentiated 3T3-L1 adipocytes by using Oil Red O staining and glycerol release measurement. GBR extract using hexane showed the highest inhibitory effect (13.58 ± 0.860%) at concentration of 200 μg/ml followed by hexane extract at 100 μg/ml (9.98 ± 1.048%) while ethyl acetate extract showed the lowest (2.62 ± 0.677%) at concentration of 200 μg/ml on pancreatic lipase activity. Water extract at 300 μg/ml showed 61.55 ± 3.824% of Oil Red O staining material (OROSM), a marker of adipogenesis. It significantly decrease (p lipolysis with 1.22-1.83 fold of greater glycerol release than control. GBR extracts especially the least polar and intermediate polar solvent extracts exhibited inhibitory effect on pancreatic lipase, decrease fat accumulation by adipocyte differentiation inhibition, and stimulate lipolysis on adipocytes. Therefore, GBR could be furthered study and developed as a functional food in helping the treatment and/or prevention of obesity.

  13. Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin Resistance and Inflammation in Male Mice

    OpenAIRE

    Schoiswohl, Gabriele; Stefanovic-Racic, Maja; Menke, Marie N.; Wills, Rachel C.; Surlow, Beth A.; Basantani, Mahesh K.; Sitnick, Mitch T.; Cai, Lingzhi; Yazbeck, Cynthia F.; Stolz, Donna B.; Pulinilkunnil, Thomas; O'Doherty, Robert M.; Kershaw, Erin E.

    2015-01-01

    Emerging evidence suggests that impaired regulation of adipocyte lipolysis contributes to the proinflammatory immune cell infiltration of metabolic tissues in obesity, a process that is proposed to contribute to the development and exacerbation of insulin resistance. To test this hypothesis in vivo, we generated mice with adipocyte-specific deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme catalyzing triacylglycerol hydrolysis. In contrast to previous models, adiponecti...

  14. Effects and Molecular Mechanism of GST-Irisin on Lipolysis and Autocrine Function in 3T3-L1 Adipocytes.

    Directory of Open Access Journals (Sweden)

    Shanshan Gao

    Full Text Available Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of the medical and scientific community. However, the signaling pathway of irisin and the molecular mechanisms responsible for the lipolysis effect remain unclear. In this study, we established an efficient system for the expression and purification of GST-irisin in Escherichia coli. The biological activity of GST-irisin was verified using the cell counting kit-8 assay and by detecting the mRNA expression of uncoupling protein 1. Our data showed that GST-irisin regulates mRNA levels of lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase and proteins such as the fatty acid-binding protein 4, leading to increased secretion of glycerol and decreased lipid accumulation in 3T3-L1 adipocytes. In addition, exogenous GST-irisin can increase its autocrine function in vitro by regulating the expression of fibronectin type III domain-containing protein 5. GST-irisin could regulate glucose uptake in 3T3-L1 adipocytes. Hence, we believe that recombinant GST-irisin could promote lipolysis and its secretion in vitro and can potentially prevent obesity and related metabolic diseases.

  15. Fas activates lipolysis in a Ca2+-CaMKII-dependent manner in 3T3-L1 adipocytes.

    Science.gov (United States)

    Rapold, Reto A; Wueest, Stephan; Knoepfel, Adrian; Schoenle, Eugen J; Konrad, Daniel

    2013-01-01

    Fas (CD95) is a member of the tumor necrosis factor (TNF) receptor superfamily and plays a crucial role in the induction of apoptosis. However, like TNF, Fas can induce nonapoptotic signaling pathways. We previously demonstrated that mice lacking Fas specifically in adipocytes are partly protected from diet-induced insulin resistance, potentially via decreased delivery of FAs to the liver, as manifested by lower total liver ceramide content. In the present study, we aimed to delineate the signaling pathway involved in Fas-mediated adipocyte lipid mobilization. Treatment of differentiated 3T3-L1 adipocytes with membrane-bound Fas ligand (FasL) significantly increased lipolysis after 12 h without inducing apoptosis. In parallel, Fas activation increased phosphorylation of ERK1/2, and FasL-induced lipolysis was blunted in the presence of the ERK-inhibitor U0126 or in ERK1/2-depleted adipocytes. Furthermore, Fas activation increased phosphorylation of the Ca(2+)/calmodulin-dependent protein kinases II (CaMKII), and blocking of the CaMKII-pathway (either by the Ca(2+) chelator BAPTA or by the CaMKII inhibitor KN62) blunted FasL-induced ERK1/2 phosphorylation and glycerol release. In conclusion, we propose a novel role for CaMKII in promoting lipolysis in adipocytes.

  16. Astragaloside IV attenuates lipolysis and improves insulin resistance induced by TNFalpha in 3T3-L1 adipocytes.

    Science.gov (United States)

    Jiang, Boren; Yang, Ying; Jin, Hua; Shang, Wenbin; Zhou, Libin; Qian, Lei; Chen, Mingdao

    2008-11-01

    Increased circulating free fatty acid (FFA) concentrations have been demonstrated to potentially link obesity, insulin resistance and cardiovascular diseases. Astragaloside IV (AS-IV) is a saponin which is widely used in traditional Chinese medicine to treat type 2 diabetes and cardiovascular diseases. The purpose of the present study was to examine the effects of AS-IV on the lipolysis and insulin resistance induced by tumor necrosis factor-alpha (TNFalpha) in cultured 3T3-L1 adipocytes. TNFalpha promotes lipolysis in mammal adipocytes via the mitogen activated protein kinase (MAPK) family resulting in reduced expression/function of perilipin. Application of AS-IV inhibited TNFalpha-induced accelerated lipolysis in a dose-dependent manner, which was compatible with suppressed phosphorylation of ERK1/2 and reversed the downregulation of perilipin. Moreover, TNFalpha induced downregulation of key enzymes in lipogenesis, including LPL, FAS and GPAT, were also attenuated by AS-IV. Further studies showed that AS-IV improved TNFalpha-induced insulin resistance in 3T3-L1 adipocytes. This study provides the first direct evidence of the antilipolytic action of AS-IV in adipocytes, which may allow this agent to decrease the circulating FFA levels, thus increase insulin sensitivity and treat cardiovascular diseases.

  17. The effects of Bee Venom and Sweet Bee Venom to the preadipocyte proliferation and lipolysis of adipocyte, localized fat accumulation

    Directory of Open Access Journals (Sweden)

    Min-Ki Kim

    2007-12-01

    Full Text Available Objectives : The purpose of this study was to investigate the effects of Bee Venom and Sweet Bee Venom to the primary cultured preadipocyte, adipocytes, and localized fat tissue. Methods : Decreased preadipocyte proliferation and decreased lipogenesis are mechanisms to reduce obesity. So, preadipocytes and adipocytes were performed on cell cultures using Sprague-Dawley Rats and treated with 0.01-1mg/㎖ Bee Venom and Sweet Bee Venom. And porcine skin including fat tissue after treated Bee Venom and Sweet Bee Venom according to the dosage dependent variation are investigated the histologic changes after injection of these Pharmacopuncture. Result : Following results were obtained from the preadipocyte proliferation and lipolysis of adipocyte and histologic investigation of fat tissue. 1. Bee Venom and Sweet Bee Venom showed the effect of decreased preadipocyte proliferation depend on concentration. 2. Bee Venom and Sweet Bee Venom showed the effect of decreased the activity of glycerol-3-phosphate dehydrogenase(GPDH significantly. 3. Bee Venom was not showed the effect of lipolysis, but Sweet Bee Venom was increased in low dosage and decreased in high dosage. 4. Investigated the histologic changes in porcine fat tissue after treated Bee Venom and Sweet Bee Venom, we knew that these Pharmacopuncture was activated nonspecific lysis of cell membranes depend on concentration. Conclusion : These results suggest that Bee Venom and Sweet Bee Venom efficiently induces decreased proliferation of preadipocyte and lipolysis in adipose tissue

  18. Increased lipolysis and altered lipid homeostasis protect γ-synuclein–null mutant mice from diet-induced obesity

    Science.gov (United States)

    Millership, Steven; Ninkina, Natalia; Guschina, Irina A.; Norton, Jessica; Brambilla, Riccardo; Oort, Pieter J.; Adams, Sean H.; Dennis, Rowena J.; Voshol, Peter J.; Rochford, Justin J.; Buchman, Vladimir L.

    2012-01-01

    Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. γ-Synuclein is highly expressed in human white adipose tissue and increased in obesity. Here we show that γ-synuclein is nutritionally regulated in white adipose tissue whereas its loss partially protects mice from high-fat diet (HFD)–induced obesity and ameliorates some of the associated metabolic complications. Compared with HFD-fed WT mice, HFD-fed γ-synuclein–null mutant mice display increased lipolysis, lipid oxidation, and energy expenditure, and reduced adipocyte hypertrophy. Knockdown of γ-synuclein in adipocytes causes redistribution of the key lipolytic enzyme ATGL to lipid droplets and increases lipolysis. γ-Synuclein–deficient adipocytes also contain fewer SNARE complexes of a type involved in lipid droplet fusion. We hypothesize that γ-synuclein may deliver SNAP-23 to the SNARE complexes under lipogenic conditions. Via these independent but complementary roles, γ-synuclein may coordinately modulate lipid storage by influencing lipolysis and lipid droplet formation. Our data reveal γ-synuclein as a regulator of lipid handling in adipocytes, the function of which is particularly important in conditions of nutrient excess. PMID:23213245

  19. Increased lipolysis and altered lipid homeostasis protect γ-synuclein-null mutant mice from diet-induced obesity.

    Science.gov (United States)

    Millership, Steven; Ninkina, Natalia; Guschina, Irina A; Norton, Jessica; Brambilla, Riccardo; Brambilla, Ricardo; Oort, Pieter J; Adams, Sean H; Dennis, Rowena J; Voshol, Peter J; Rochford, Justin J; Buchman, Vladimir L

    2012-12-18

    Synucleins are a family of homologous proteins principally known for their involvement in neurodegeneration. γ-Synuclein is highly expressed in human white adipose tissue and increased in obesity. Here we show that γ-synuclein is nutritionally regulated in white adipose tissue whereas its loss partially protects mice from high-fat diet (HFD)-induced obesity and ameliorates some of the associated metabolic complications. Compared with HFD-fed WT mice, HFD-fed γ-synuclein-null mutant mice display increased lipolysis, lipid oxidation, and energy expenditure, and reduced adipocyte hypertrophy. Knockdown of γ-synuclein in adipocytes causes redistribution of the key lipolytic enzyme ATGL to lipid droplets and increases lipolysis. γ-Synuclein-deficient adipocytes also contain fewer SNARE complexes of a type involved in lipid droplet fusion. We hypothesize that γ-synuclein may deliver SNAP-23 to the SNARE complexes under lipogenic conditions. Via these independent but complementary roles, γ-synuclein may coordinately modulate lipid storage by influencing lipolysis and lipid droplet formation. Our data reveal γ-synuclein as a regulator of lipid handling in adipocytes, the function of which is particularly important in conditions of nutrient excess.

  20. miR-378 Activates the Pyruvate-PEP Futile Cycle and Enhances Lipolysis to Ameliorate Obesity in Mice.

    Science.gov (United States)

    Zhang, Yong; Li, Changyin; Li, Hu; Song, Yipeng; Zhao, Yixia; Zhai, Lili; Wang, Haixia; Zhong, Ran; Tang, Huiru; Zhu, Dahai

    2016-03-01

    Obesity has been linked to many health problems, such as diabetes. However, there is no drug that effectively treats obesity. Here, we reveal that miR-378 transgenic mice display reduced fat mass, enhanced lipolysis, and increased energy expenditure. Notably, administering AgomiR-378 prevents and ameliorates obesity in mice. We also found that the energy deficiency seen in miR-378 transgenic mice was due to impaired glucose metabolism. This impairment was caused by an activated pyruvate-PEP futile cycle via the miR-378-Akt1-FoxO1-PEPCK pathway in skeletal muscle and enhanced lipolysis in adipose tissues mediated by miR-378-SCD1. Our findings demonstrate that activating the pyruvate-PEP futile cycle in skeletal muscle is the primary cause of elevated lipolysis in adipose tissues of miR-378 transgenic mice, and it helps orchestrate the crosstalk between muscle and fat to control energy homeostasis in mice. Thus, miR-378 may serve as a promising agent for preventing and treating obesity in humans.

  1. Inhibition of gastrointestinal lipolysis by green tea, coffee, and gomchui (Ligularia fischeri) tea polyphenols during simulated digestion.

    Science.gov (United States)

    Cha, Kwang Hyun; Song, Dae-Geun; Kim, Sang Min; Pan, Cheol-Ho

    2012-07-25

    Green tea, coffee, and gomchui (Ligularia fischeri) tea, which are rich in polyphenols, may exhibit antiobesity effects by inhibiting pancreatic lipase. However, the bioavailability of some polyphenols is poor due to either degradation or absorption difficulties in the gastrointestinal tract, thus making their beneficial effects doubtful. This study was conducted to evaluate the inhibitory effect of three beverages on lipolysis and the contribution of their major polyphenols during simulated digestion. During simulated digestion, gomchui tea was the most potent at inhibiting gastrointestinal lipolysis, whereas green tea was the least potent. The strongest lipase inhibitor among purified major polyphenols was a green tea polyphenol, (-)-epigallocatechin gallate (EGCG, IC(50) = 1.8 ± 0.57 μM), followed by di-O-caffeoylquinic acid isomers (DCQA, IC(50) from 12.7 ± 4.5 to 40.4 ± 2.3 μM), which are gomchui tea polyphenols. However, the stability of DCQA was greater than that of EGCG when subjected to simulated digestion. Taken together, gomchui tea, which has DCQA as the major polyphenol, showed stronger lipolysis inhibitory activity during simulated digestion compared to both green tea and coffee.

  2. Aculeatin, a coumarin derived from Toddalia asiatica (L.) Lam., enhances differentiation and lipolysis of 3T3-L1 adipocytes

    Energy Technology Data Exchange (ETDEWEB)

    Watanabe, Akio, E-mail: watanabea@jfrl.or.jp [Japan Food Research Laboratories, Osaka 567-0085 (Japan); Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555 (Japan); Kato, Tsuyoshi; Ito, Yusuke; Yoshida, Izumi; Harada, Teppei; Mishima, Takashi; Fujita, Kazuhiro; Watai, Masatoshi [Japan Food Research Laboratories, Osaka 567-0085 (Japan); Nakagawa, Kiyotaka; Miyazawa, Teruo [Food and Biodynamic Chemistry Laboratory, Graduate School of Agricultural Science, Tohoku University, Miyagi 981-8555 (Japan)

    2014-10-31

    Highlights: • Aculeatin promoted adipocyte differentiation. • Aculeatin improved glucose uptake. • Aculeatin enhanced adipocyte lipolysis. - Abstract: Toddalia asiatica (L.) Lam. (T. asiatica) has been utilized traditionally for medicinal purposes such as the treatment of diabetes. Currently, the extract is considered to be a good source of anti-diabetic agents, but the active compounds have yet to be identified. In this study, we investigated the effects of fractionated T. asiatica extracts on the differentiation of 3T3-L1 preadipocytes and identified aculeatin as a potential active agent. When 3T3-L1 preadipocytes were treated with aculeatin isolated from T. asiatica in the presence of insulin, aculeatin increased cellular triglyceride levels and glycerol-3-phosphate dehydrogenase activity. This indicated that aculeatin could enhance the differentiation of preadipocytes into adipocytes. Further analyses using a DNA microarray and real-time quantitative reverse-transcription PCR showed an increase in the expression of peroxisome proliferator-activated receptor-γ target genes (Pparg, Ap2, Cd36, Glut4 and Adipoq) by aculeatin, suggesting that aculeatin enhances the differentiation of 3T3-L1 cells by modulating the expression of genes critical for adipogenesis. Interestingly, after treatment of differentiated adipocytes with aculeatin, glucose uptake and lipolysis were enhanced. Overall, our results suggested that aculeatin is an active compound in T. asiatica for enhancing both differentiation and lipolysis of adipocytes, which are useful for the treatment of lipid abnormalities as well as diabetes.

  3. Effects and Molecular Mechanism of GST-Irisin on Lipolysis and Autocrine Function in 3T3-L1 Adipocytes.

    Science.gov (United States)

    Gao, Shanshan; Li, Fangmin; Li, Huimin; Huang, Yibing; Liu, Yu; Chen, Yuxin

    2016-01-01

    Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of the medical and scientific community. However, the signaling pathway of irisin and the molecular mechanisms responsible for the lipolysis effect remain unclear. In this study, we established an efficient system for the expression and purification of GST-irisin in Escherichia coli. The biological activity of GST-irisin was verified using the cell counting kit-8 assay and by detecting the mRNA expression of uncoupling protein 1. Our data showed that GST-irisin regulates mRNA levels of lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase and proteins such as the fatty acid-binding protein 4, leading to increased secretion of glycerol and decreased lipid accumulation in 3T3-L1 adipocytes. In addition, exogenous GST-irisin can increase its autocrine function in vitro by regulating the expression of fibronectin type III domain-containing protein 5. GST-irisin could regulate glucose uptake in 3T3-L1 adipocytes. Hence, we believe that recombinant GST-irisin could promote lipolysis and its secretion in vitro and can potentially prevent obesity and related metabolic diseases.

  4. Characteristics of lipolysis in white adipose tissues of SHR/NDmc-cp rats, a model of metabolic syndrome.

    Science.gov (United States)

    Harikai, Naoki; Hashimoto, Ayu; Semma, Masanori; Ichikawa, Atsushi

    2007-06-01

    This study shows the characteristics of hormone-dependent lipolysis in white adipose tissues from corpulent spontaneously hypertensive rats (SHR/NDmc-cp(cp/cp)). The glycerol-releasing activity on addition of norepinephrine (NE) and corticotropin (ACTH) was diminished in slices of epididymal, retroperitoneal, and mesenteric adipose tissues from cp/cp rats compared with those from Wistar Kyoto rats and lean spontaneous hypertensive rats (SHR/NDmc-cp(+/+)). 8-Bromo-cyclic adenosine monophosphate had a slight effect on lipolysis in epididymal, retroperitoneal, and mesenteric adipose tissues from cp/cp rats, and addition of NE and ACTH resulted in a slight accumulation of cyclic adenosine monophosphate in epididymal adipose tissue from cp/cp rats. Therefore, the alteration of hormone-dependent lipolysis-related genes was analyzed using quantitative real-time polymerase chain reaction. It was found that the expression of beta(3)-adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and perilipin messenger RNAs was limited in epididymal, retroperitoneal, mesenteric, and subcutaneous adipose tissues from cp/cp rats compared with +/+ rats. These results indicate that in white adipose tissue from cp/cp rats, the diminished lipolytic response to NE and ACTH may be caused by impaired expression of beta(3)-adrenergic receptor, melanocortin 2 receptor, hormone-sensitive lipase, and perilipin.

  5. miR-378 Activates the Pyruvate-PEP Futile Cycle and Enhances Lipolysis to Ameliorate Obesity in Mice

    Directory of Open Access Journals (Sweden)

    Yong Zhang

    2016-03-01

    Full Text Available Obesity has been linked to many health problems, such as diabetes. However, there is no drug that effectively treats obesity. Here, we reveal that miR-378 transgenic mice display reduced fat mass, enhanced lipolysis, and increased energy expenditure. Notably, administering AgomiR-378 prevents and ameliorates obesity in mice. We also found that the energy deficiency seen in miR-378 transgenic mice was due to impaired glucose metabolism. This impairment was caused by an activated pyruvate-PEP futile cycle via the miR-378-Akt1-FoxO1-PEPCK pathway in skeletal muscle and enhanced lipolysis in adipose tissues mediated by miR-378-SCD1. Our findings demonstrate that activating the pyruvate-PEP futile cycle in skeletal muscle is the primary cause of elevated lipolysis in adipose tissues of miR-378 transgenic mice, and it helps orchestrate the crosstalk between muscle and fat to control energy homeostasis in mice. Thus, miR-378 may serve as a promising agent for preventing and treating obesity in humans.

  6. Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and lipolysis--a cohort study.

    Science.gov (United States)

    Nilsson, Maria; Dahlman, Ingrid; Jiao, Hong; Gustafsson, Jan-Ake; Arner, Peter; Dahlman-Wright, Karin

    2007-12-04

    The estrogen receptors alpha and beta (ESR1, ESR2) have been implicated in adiposity, lipid metabolism and feeding behaviour. In this report we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1 SNPs to adipocyte lipolysis and lipogenesis phenotypes. 23 ESR1 and 11 ESR2 tag-SNPs, covering most of the common haplotype variation in each gene according to HAPMAP data, were analysed by Chi2 for association with obesity in a cohort comprising 705 adults with severe obesity and 402 lean individuals. Results were replicated in a cohort comprising 837 obese and 613 lean subjects. About 80% of both cohorts comprised women and 20% men. Adipose tissue ESR1 mRNA was quantified in 122 women and related to lipolysis and lipogenesis by multiple regression. ESR1 SNPs were analysed for association with adipocyte lipolysis and lipogenesis phenotypes in 204 obese women by simple regression. No ESR1 SNP was associated with obesity. Five ESR2 SNPs displayed nominal significant allelic association with obesity in women and one in men. The two ESR2 SNPs associated with obesity with nominal P value obesity was observed. There was an inverse correlation between ESR1 mRNA levels in abdominal subcutaneous (sc) adipose tissue and basal lipolysis, as well as responsiveness to adrenoceptor agonists independent of age and BMI (P value 0.009-0.045). ESR1 rs532010 was associated with lipolytic sensitivity to noradrenaline (nominal P value 0.012), and ESR1 rs1884051 with responsiveness to the non-selective beta-adrenoceptor agonist isoprenaline (nominal P value 0.05). These associations became non-significant after Bonferroni correction. ESR1 gene alleles are unlikely to be a major cause of obesity in women. A minor importance of ESR2 on severe obesity cannot be excluded. The inverse correlation between ESR1 mRNA levels and lipolytic responsiveness to adrenoceptor agonists implies that low adipose

  7. Impact of estrogen receptor gene polymorphisms and mRNA levels on obesity and lipolysis – a cohort study

    Science.gov (United States)

    Nilsson, Maria; Dahlman, Ingrid; Jiao, Hong; Gustafsson, Jan-Åke; Arner, Peter; Dahlman-Wright, Karin

    2007-01-01

    Background The estrogen receptors α and β (ESR1, ESR2) have been implicated in adiposity, lipid metabolism and feeding behaviour. In this report we analyse ESR1 and ESR2 gene single nucleotide polymorphisms (SNPs) for association with obesity. We also relate adipose tissue ESR1 mRNA levels and ESR1 SNPs to adipocyte lipolysis and lipogenesis phenotypes. Methods 23 ESR1 and 11 ESR2 tag-SNPs, covering most of the common haplotype variation in each gene according to HAPMAP data, were analysed by Chi2 for association with obesity in a cohort comprising 705 adults with severe obesity and 402 lean individuals. Results were replicated in a cohort comprising 837 obese and 613 lean subjects. About 80% of both cohorts comprised women and 20% men. Adipose tissue ESR1 mRNA was quantified in 122 women and related to lipolysis and lipogenesis by multiple regression. ESR1 SNPs were analysed for association with adipocyte lipolysis and lipogenesis phenotypes in 204 obese women by simple regression. Results No ESR1 SNP was associated with obesity. Five ESR2 SNPs displayed nominal significant allelic association with obesity in women and one in men. The two ESR2 SNPs associated with obesity with nominal P value obesity was observed. There was an inverse correlation between ESR1 mRNA levels in abdominal subcutaneous (sc) adipose tissue and basal lipolysis, as well as responsiveness to adrenoceptor agonists independent of age and BMI (P value 0.009–0.045). ESR1 rs532010 was associated with lipolytic sensitivity to noradrenaline (nominal P value 0.012), and ESR1 rs1884051 with responsiveness to the non-selective beta-adrenoceptor agonist isoprenaline (nominal P value 0.05). These associations became non-significant after Bonferroni correction. Conclusion ESR1 gene alleles are unlikely to be a major cause of obesity in women. A minor importance of ESR2 on severe obesity cannot be excluded. The inverse correlation between ESR1 mRNA levels and lipolytic responsiveness to adrenoceptor

  8. Basal lipolysis, not the degree of insulin resistance, differentiates large from small isolated adipocytes in high-fat fed mice.

    Science.gov (United States)

    Wueest, S; Rapold, R A; Rytka, J M; Schoenle, E J; Konrad, D

    2009-03-01

    Adipocytes in obesity are characterised by increased cell size and insulin resistance compared with adipocytes isolated from lean patients. However, it is not clear at present whether hypertrophy actually does drive adipocyte insulin resistance. Thus, the aim of the present study was to metabolically characterise small and large adipocytes isolated from epididymal fat pads of mice fed a high-fat diet (HFD). C57BL/6J mice were fed normal chow or HFD for 8 weeks. Adipocytes from epididymal fat pads were isolated by collagenase digestion and, in HFD-fed mice, separated into two fractions according to their size by filtration through a nylon mesh. Viability was assessed by lactate dehydrogenase and 3-(4,5-dimethylthiazol-2-yl)-2, 5-diphenyltetrazolium assays. Basal and insulin-stimulated D-[U-(14)C]glucose incorporation and lipolysis were measured. Protein levels and mRNA expression were determined by western blot and real-time RT-PCR, respectively. Insulin-stimulated D-[U-(14)C]glucose incorporation into adipocytes isolated from HFD-fed mice was reduced by 50% compared with adipocytes from chow-fed mice. However, it was similar between small (average diameter 60.9 +/- 3.1 microm) and large (average diameter 83.0 +/- 6.6 microm) adipocytes. Similarly, insulin-stimulated phosphorylation of protein kinase B and AS160 were reduced to the same extent in small and large adipocytes isolated from HFD-mice. In addition, insulin failed to inhibit lipolysis in both adipocyte fractions, whereas it decreased lipolysis by 30% in adipocytes of chow-fed mice. In contrast, large and small adipocytes differed in basal lipolysis rate, which was twofold higher in the larger cells. The latter finding was associated with higher mRNA expression levels of Atgl (also known as Pnpla2) and Hsl (also known as Lipe) in larger adipocytes. Viability was not different between small and large adipocytes. Rate of basal lipolysis but not insulin responsiveness is different between small and large

  9. Analysis of raw milk quality at reception and during cold storage: combined effects of somatic cell counts and psychrotrophic bacteria on lipolysis.

    Science.gov (United States)

    Gargouri, Ahmed; Hamed, Houda; Elfeki, Abdelfettah

    2013-09-01

    The objective of the article was to analyze the influence of psychrotrophic bacteria counts (PBCs) and somatic cell counts (SCCs) on the extent of lipolysis in bulk samples of cow's milk at reception and during cold storage. Samples of milk were analyzed on the day of sampling and subsequently during cold storage. The acidity, fat, density, chloride content, electrical conductivity (EC), bulk milk SCCs (BMSCC), and PBC values were analyzed on the day of sampling and the levels of acidity, EC, SCC, and PBC were analyzed during cold storage at 4 °C for 72 h. The SCC value 869 × 10(3) mL(-1) was higher than the recommended threshold. Lipolysis level at sampling day was related more closely with SCC than with PBC. There was no significant correlation between milk acidity and PBC among others parameters, while the milk mean density was only significant (P < 0.01) correlated with the fat content. The EC and chloride content were consistently correlated (P < 0.001) with BMSCC that allowed them to be used as indicators of mammary gland infection. The milk acidity, EC, PBC, and lipolysis levels increased in relation to the storage time at 4 °C. The lipolysis level during storage was in closer relation to the SCC, but not relation to the PBC. Effects of SCC and PBC on lipolysis decreased throughout the chilling period. It was concluded that initial lipolysis level and intrinsic milk lipoprotein lipase appear more effective than SCC and PBC on the development of lipolysis during storage.

  10. Impaired adipose tissue lipid storage, but not altered lipolysis, contributes to elevated levels of NEFA in type 2 diabetes. Degree of hyperglycemia and adiposity are important factors.

    Science.gov (United States)

    Pereira, Maria J; Skrtic, Stanko; Katsogiannos, Petros; Abrahamsson, Niclas; Sidibeh, Cherno O; Dahgam, Santosh; Månsson, Marianne; Risérus, Ulf; Kullberg, Joel; Eriksson, Jan W

    2016-12-01

    Elevated levels of circulating non-esterified fatty acids (NEFA) mediate many adverse metabolic effects. In this work we aim to determine the impact of type 2 diabetes (T2D), glycemic control and obesity on lipolysis regulation. 20 control and 20 metformin-treated T2D subjects were matched for sex (10M/10 F), age (58±11 vs 58±9 y) and BMI (30.8±4.6 vs 30.7±4.9kg/m(2)). In vivo lipolysis was assessed during a 3h-OGTT with plasma glycerol and NEFA levels. Subcutaneous adipose tissue (SAT) biopsies were obtained to measure mRNA and metabolite levels of factors related to lipolysis and lipid storage and to assess in vitro lipolysis in isolated subcutaneous adipocytes. Plasma NEFA AUC during the OGTT where higher 30% (P=0.005) in T2D than in control subjects, but plasma glycerol AUC and subcutaneous adipocyte lipolysis in vitro were similar, suggesting that adipose tissue lipolysis is not altered. Expression in SAT of genes involved in lipid storage (FABP4, DGAT1, FASN) were reduced in T2D subjects compared with controls, but no differences were seen for genes involved in lipolysis. T2D subjects had elevated markers of beta-oxidation, α-hydroxybutyrate (1.4-fold, Plipolysis or lipid beta-oxidation. Impaired adipose NEFA re-esterification or de novo lipogenesis is likely to contribute to higher NEFA plasma levels in T2D. The data suggest that hyperglycemia and adiposity are important contributing factors for the regulation of plasma NEFA concentrations. Copyright © 2016 Elsevier Inc. All rights reserved.

  11. The effect of inhibition of endoplasmic reticulum stress on lipolysis in white adipose tissue in a rat model of chronic kidney disease.

    Science.gov (United States)

    Zhu, Yan; Chen, Yu-ling; Li, Cong; Ding, Xiao-yan; Xu, Guo-yu; Hu, Li-li; Hou, Fan-fan; Zhou, Qiu-gen

    2014-03-01

    Lipolysis in fat tissue plays an important role in the development of metabolic disturbances, a characteristic feature of chronic kidney disease (CKD). In the present study, we tested the hypothesis that the inhibition of endoplasmic reticulum (ER) stress could alleviate lipolysis in white adipose tissue in a rat model of CKD. A rat model of CKD was established by a method of reduced renal mass (RRM). Lipolysis was measured as the release of glycerol in ex vivo fat pads and cultured primary adipocytes. The activity of lipases and markers of ER stress were measured by Western blotting and immunoprecipitation. Our data showed that lipolysis in visceral white adipose tissue was increased in RRM rats compared with control rats. In addition, increased phosphorylation of hormone-sensitive lipase (HSL) and binding of adipose triglyceride lipase (ATGL) to comparative gene identification-58 (CGI-58) protein were observed in the RRM rats. The phosphorylation of ER stress markers, including IRE1α, PERK, and eukaryotic initiation factor (eIF) 2α, and the expression of ER stress marker 78 kDa glucose-regulated protein (GRP78) were significantly increased in RRM rats. Treatment with an inhibitor of ER stress partially but significantly alleviated lipolysis, and this alleviation was accompanied by reduced binding of ATGL to CGI-58. Our results showed that enhanced lipolysis and ER stress occurred in visceral white adipose tissue in a rat model of CKD. Moreover, inhibition of ER stress significantly alleviated lipolysis. These findings suggest that ER stress is a potential therapeutic target for the metabolic disturbances associated with CKD.

  12. Butyric acid released during milk lipolysis triggers biofilm formation of Bacillus species.

    Science.gov (United States)

    Pasvolsky, Ronit; Zakin, Varda; Ostrova, Ievgeniia; Shemesh, Moshe

    2014-07-02

    Bacillus species form biofilms within milking pipelines and on surfaces of equipment in the dairy industry which represent a continuous hygiene problem and can lead to serious economic losses due to food spoilage and equipment impairment. Although much is known about the mechanism by which the model organism Bacillus subtilis forms biofilms in laboratory mediums in vitro, little is known of how these biofilms are formed in natural environments such as milk. Besides, little is known of the signaling pathways leading to biofilm formation in other Bacillus species, such as Bacillus cereus and Bacillus licheniformis, both of which are known to contaminate milk. In this study, we report that milk triggers the formation of biofilm-related structures, termed bundles. We show this to be a conserved phenomenon among all Bacillus members tested. Moreover, we demonstrate that the tasA gene, which encodes a major portion of the matrix which holds the biofilm together, is vital for this process. Furthermore, we show that the free fatty acid (FFA) - butyric acid (BA), which is released during lipolysis of milk fat and demonstrates antimicrobial activity, is the potent trigger for biofilm bundle formation. We finally show that BA-triggered biofilm bundle formation is mediated by the histidine kinase, KinD. Taken together, these observations indicate that BA, which is a major FFA within milk triggers biofilm formation in a conserved mechanism among members of the Bacillus genus.

  13. Aerobic training improves exercise-induced lipolysis in SCAT and lipid utilization in overweight men.

    Science.gov (United States)

    de Glisezinski, I; Moro, C; Pillard, F; Marion-Latard, F; Harant, I; Meste, M; Berlan, M; Crampes, F; Rivière, D

    2003-11-01

    The aim of this study was to investigate whether endurance training improves lipid mobilization and oxidation in overweight subjects. Eleven young men (25.6 +/- 1.4 yr and body mass index 27.7 +/- 0.2) performed a 4-mo training program consisting of practicing aerobic exercise 5 days/wk. Before and after the training period, lipid oxidation was explored during a 60-min exercise at 50% of peak O2 consumption by use of indirect calorimetry. Lipid mobilization and antilipolytic alpha2-adrenoceptor effect were also studied using the microdialysis method in abdominal subcutaneous adipose tissue (SCAT). After training, plasma nonesterified fatty acid (NEFA) levels, at rest and during exercise, were significantly lower than before (P < 0.001). Lipolysis in SCAT was significantly higher after than before training. An antilipolytic alpha2-adrenoceptor effect in SCAT was underlined during exercise before training and disappeared after. The respiratory exchange ratio was lower after training, i.e., the percentage of lipid oxidation was higher only at rest. The amount of lipid oxidized was higher after training, at rest, and during exercise. Although exercise power was higher after training, the relative intensity was equivalent, as suggested by a similar increase in plasma catecholamine concentrations before and after training. In conclusion, 4-mo training in overweight men improved lipid mobilization through a decrease of antilipolytic alpha2-adrenoceptor effect in SCAT and lipid oxidation during moderate exercise. Training induced a decrease of blood NEFA, predicting better prevention of obesity.

  14. Catecholamine effects on lipolysis and blood flow in human abdominal and femoral adipose tissue.

    Science.gov (United States)

    Millet, L; Barbe, P; Lafontan, M; Berlan, M; Galitzky, J

    1998-07-01

    With the use of the microdialysis method, the present study, performed on young, healthy, nonobese subjects of both genders, compares the effects of locally infused catecholamines on glycerol concentration and blood flow in abdominal (Abd) and femoral (Fem) adipose tissue. Physiological activation of the sympathetic nervous system through active tilt was also investigated. In both genders, extracellular glycerol concentration was higher in Fem than in Abd adipose tissue. Local blood flow was lower in Fem than in Abd adipose tissue. Isoproterenol perfusion increased extracellular glycerol levels, but no differences were found by gender or fat-deposit site. Isoproterenol induced a greater increase in local blood flow in Fem adipose tissue in both genders. Epinephrine and norepinephrine perfusion increased extracellular glycerol and reduced blood flow. No major differences were found according to gender and fat-deposit site. Active tilt increased plasma glycerol, free fatty acid, norepinephrine levels, and extracellular glycerol concentration to the same extent whatever the gender and fat deposit. Thus, Fem adipose tissue is characterized by a higher extracellular glycerol concentration and a lower blood flow than is Abd tissue in men and women. In these tissues, in situ lipolysis and local blood flow were similar in response to adrenergic stimulation.

  15. Simplified assays of lipolysis enzymes for drug discovery and specificity assessment of known inhibitors.

    Science.gov (United States)

    Iglesias, Jose; Lamontagne, Julien; Erb, Heidi; Gezzar, Sari; Zhao, Shangang; Joly, Erik; Truong, Vouy Linh; Skorey, Kathryn; Crane, Sheldon; Madiraju, S R Murthy; Prentki, Marc

    2016-01-01

    Lipids are used as cellular building blocks and condensed energy stores and also act as signaling molecules. The glycerolipid/ fatty acid cycle, encompassing lipolysis and lipogenesis, generates many lipid signals. Reliable procedures are not available for measuring activities of several lipolytic enzymes for the purposes of drug screening, and this resulted in questionable selectivity of various known lipase inhibitors. We now describe simple assays for lipolytic enzymes, including adipose triglyceride lipase (ATGL), hormone sensitive lipase (HSL), sn-1-diacylglycerol lipase (DAGL), monoacylglycerol lipase, α/β-hydrolase domain 6, and carboxylesterase 1 (CES1) using recombinant human and mouse enzymes either in cell extracts or using purified enzymes. We observed that many of the reported inhibitors lack specificity. Thus, Cay10499 (HSL inhibitor) and RHC20867 (DAGL inhibitor) also inhibit other lipases. Marked differences in the inhibitor sensitivities of human ATGL and HSL compared with the corresponding mouse enzymes was noticed. Thus, ATGListatin inhibited mouse ATGL but not human ATGL, and the HSL inhibitors WWL11 and Compound 13f were effective against mouse enzyme but much less potent against human enzyme. Many of these lipase inhibitors also inhibited human CES1. Results describe reliable assays for measuring lipase activities that are amenable for drug screening and also caution about the specificity of the many earlier described lipase inhibitors.

  16. Sexual dimorphic regulation of body weight dynamics and adipose tissue lipolysis.

    Science.gov (United States)

    Benz, Verena; Bloch, Mandy; Wardat, Sami; Böhm, Christian; Maurer, Lukas; Mahmoodzadeh, Shokoufeh; Wiedmer, Petra; Spranger, Joachim; Foryst-Ludwig, Anna; Kintscher, Ulrich

    2012-01-01

    Successful reduction of body weight (BW) is often followed by recidivism to obesity. BW-changes including BW-loss and -regain is associated with marked alterations in energy expenditure (EE) and adipose tissue (AT) metabolism. Since these processes are sex-specifically controlled, we investigated sexual dimorphisms in metabolic processes during BW-dynamics (gain-loss-regain). Obesity was induced in C57BL/6J male (m) and female (f) mice by 15 weeks high-fat diet (HFD) feeding. Subsequently BW was reduced (-20%) by caloric restriction (CR) followed by adaptive feeding, and a regain-phase. Measurement of EE, body composition, blood/organ sampling were performed after each feeding period. Lipolysis was analyzed ex-vivo in gonadal AT. Male mice exhibited accelerated BW-gain compared to females (relative BW-gain m:140.5±3.2%; f:103.7±6.5%; pregain faster in males than in females. The present study shows sex-specific dynamics during BW-gain-loss-regain. Female mice responded to CR with an increase in lipolytic activity, and augmented lipid-oxidation leading to more efficient weight loss. These processes likely involve ERα-dependent signaling in AT and sexual dimorphic regulation of genes involved in lipid metabolism.

  17. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes

    Science.gov (United States)

    Calderon-Dominguez, María; Sebastián, David; Fucho, Raquel; Weber, Minéia; Mir, Joan F.; García-Casarrubios, Ester; Obregón, María Jesús; Zorzano, Antonio; Valverde, Ángela M.; Serra, Dolors

    2016-01-01

    The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders. PMID:27438137

  18. The Lipid Droplet Protein Hypoxia-inducible Gene 2 Promotes Hepatic Triglyceride Deposition by Inhibiting Lipolysis*

    Science.gov (United States)

    DiStefano, Marina T.; Danai, Laura V.; Roth Flach, Rachel J.; Chawla, Anil; Pedersen, David J.; Guilherme, Adilson; Czech, Michael P.

    2015-01-01

    The liver is a major site of glucose, fatty acid, and triglyceride (TG) synthesis and serves as a major regulator of whole body nutrient homeostasis. Chronic exposure of humans or rodents to high-calorie diets promotes non-alcoholic fatty liver disease, characterized by neutral lipid accumulation in lipid droplets (LD) of hepatocytes. Here we show that the LD protein hypoxia-inducible gene 2 (Hig2/Hilpda) functions to enhance lipid accumulation in hepatocytes by attenuating TG hydrolysis. Hig2 expression increased in livers of mice on a high-fat diet and during fasting, two states associated with enhanced hepatic TG content. Hig2 expressed in primary mouse hepatocytes localized to LDs and promoted LD TG deposition in the presence of oleate. Conversely, tamoxifen-inducible Hig2 deletion reduced both TG content and LD size in primary hepatocytes from mice harboring floxed alleles of Hig2 and a cre/ERT2 transgene controlled by the ubiquitin C promoter. Hepatic TG was also decreased by liver-specific deletion of Hig2 in mice with floxed Hig2 expressing cre controlled by the albumin promoter. Importantly, we demonstrate that Hig2-deficient hepatocytes exhibit increased TG lipolysis, TG turnover, and fatty acid oxidation as compared with controls. Interestingly, mice with liver-specific Hig2 deletion also display improved glucose tolerance. Taken together, these data indicate that Hig2 plays a major role in promoting lipid sequestration within LDs in mouse hepatocytes through a mechanism that impairs TG degradation. PMID:25922078

  19. Resistin induces lipolysis and suppresses adiponectin secretion in cultured human visceral adipose tissue.

    Science.gov (United States)

    Chen, Neng; Zhou, Lingmei; Zhang, Zixiang; Xu, Jiaying; Wan, Zhongxiao; Qin, Liqiang

    2014-11-01

    Resistin is an adipokine secreted from adipose tissue, which is likely involved in the development of obesity and insulin resistance via its interaction with other organs, as well as affecting adipose tissue function. The impact of resistin treatment on lipolysis and adiponectin secretion in human visceral adipose tissue is currently unknown. Mesenteric adipose tissue samples were obtained from 14 male subjects [age 54±6 yr, body mass index (BMI) 23.59±0.44 kg/m(2)] undergoing abdominal surgeries. Adipose tissues were cultured and treated with resistin (100 ng/mL, 24h) in the absence or presence of different signaling inhibitors: H89 (1 μM), PD98059 (25 μM) and SB201290 (20 μM) for glycerol and non-esterified fatty acid (NEFA) measurement. Adiponectin level from media at 24 h was also measured via ELISA. Adipose tissue minces after resistin incubation (100 ng/mL, 24 h) were also collected for further Western blotting analysis. Resistin resulted in significant induction of glycerol (3.62±0.57 vs. 5.30±1.11 mmol/L/g tissue, ptissue, ptissue, ptissues via its effect on adipose tissue function.

  20. Adipose tissue lipolysis and energy metabolism in early cancer cachexia in mice.

    Science.gov (United States)

    Kliewer, Kara L; Ke, Jia-Yu; Tian, Min; Cole, Rachel M; Andridge, Rebecca R; Belury, Martha A

    2015-01-01

    Cancer cachexia is a progressive metabolic disorder that results in depletion of adipose tissue and skeletal muscle. A growing body of literature suggests that maintaining adipose tissue mass in cachexia may improve quality-of-life and survival outcomes. Studies of lipid metabolism in cachexia, however, have generally focused on later stages of the disorder when severe loss of adipose tissue has already occurred. Here, we investigated lipid metabolism in adipose, liver and muscle tissues during early stage cachexia - before severe fat loss - in the colon-26 murine model of cachexia. White adipose tissue mass in cachectic mice was moderately reduced (34-42%) and weight loss was less than 10% of initial body weight in this study of early cachexia. In white adipose depots of cachectic mice, we found evidence of enhanced protein kinase A - activated lipolysis which coincided with elevated total energy expenditure and increased expression of markers of brown (but not white) adipose tissue thermogenesis and the acute phase response. Total lipids in liver and muscle were unchanged in early cachexia while markers of fatty oxidation were increased. Many of these initial metabolic responses contrast with reports of lipid metabolism in later stages of cachexia. Our observations suggest intervention studies to preserve fat mass in cachexia should be tailored to the stage of cachexia. Our observations also highlight a need for studies that delineate the contribution of cachexia stage and animal model to altered lipid metabolism in cancer cachexia and identify those that most closely mimic the human condition.

  1. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes.

    Directory of Open Access Journals (Sweden)

    María Calderon-Dominguez

    Full Text Available The discovery of active brown adipose tissue (BAT in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM, a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO, in a rat brown adipocyte (rBA cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders.

  2. Carnitine Palmitoyltransferase 1 Increases Lipolysis, UCP1 Protein Expression and Mitochondrial Activity in Brown Adipocytes.

    Science.gov (United States)

    Calderon-Dominguez, María; Sebastián, David; Fucho, Raquel; Weber, Minéia; Mir, Joan F; García-Casarrubios, Ester; Obregón, María Jesús; Zorzano, Antonio; Valverde, Ángela M; Serra, Dolors; Herrero, Laura

    2016-01-01

    The discovery of active brown adipose tissue (BAT) in adult humans and the fact that it is reduced in obese and diabetic patients have put a spotlight on this tissue as a key player in obesity-induced metabolic disorders. BAT regulates energy expenditure through thermogenesis; therefore, harnessing its thermogenic fat-burning power is an attractive therapeutic approach. We aimed to enhance BAT thermogenesis by increasing its fatty acid oxidation (FAO) rate. Thus, we expressed carnitine palmitoyltransferase 1AM (CPT1AM), a permanently active mutant form of CPT1A (the rate-limiting enzyme in FAO), in a rat brown adipocyte (rBA) cell line through adenoviral infection. We found that CPT1AM-expressing rBA have increased FAO, lipolysis, UCP1 protein levels and mitochondrial activity. Additionally, enhanced FAO reduced the palmitate-induced increase in triglyceride content and the expression of obese and inflammatory markers. Thus, CPT1AM-expressing rBA had enhanced fat-burning capacity and improved lipid-induced derangements. This indicates that CPT1AM-mediated increase in brown adipocytes FAO may be a new approach to the treatment of obesity-induced disorders.

  3. An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans.

    Science.gov (United States)

    Lafontan, Max; Moro, Cédric; Sengenes, Coralie; Galitzky, Jean; Crampes, François; Berlan, Michel

    2005-10-01

    In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3', 5'-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral beta-blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.

  4. IL-6 induces lipolysis and mitochondrial dysfunction, but does not affect insulin-mediated glucose transport in 3T3-L1 adipocytes.

    Science.gov (United States)

    Ji, Chenbo; Chen, Xiaohui; Gao, Chunlin; Jiao, Liuhong; Wang, Jianguo; Xu, Guangfeng; Fu, Hailong; Guo, Xirong; Zhao, Yaping

    2011-08-01

    Interleukin-6 (IL-6) has emerged as an important cytokine involved in the regulation of metabolism. However, the role of IL-6 in the etiology of obesity and insulin resistance is not fully understood. Mitochondria are key organelles of energy metabolism, and there is growing evidence that mitochondrial dysfunction plays a crucial role in the pathogenesis of obesity-associated insulin resistance. In this study, we determined the direct effect of IL-6 on lipolysis in adipocytes, and the effects of IL-6 on mitochondrial function were investigated. We found that cells treated with IL-6 displayed fewer lipids and an elevated glycerol release rate. Further, IL-6 treatment led to decreased mitochondrial membrane potential, decreased cellular ATP production, and increased intracellular ROS levels. The mitochondria in IL-6-treated cells became swollen and hollow with reduced or missing cristae. However, insulin-stimulated glucose transport was unaltered. PGC-1α, NRF1, and mtTFA mRNA levels were markedly increased, and the mitochondrial contents were also increased. Our results demonstrate that IL-6 can exert a direct lipolytic effect and induce mitochondrial dysfunction. However, IL-6 did not affect insulin sensitivity in adipocytes in vitro. We deduce that in these cells, enhanced mitochondrial biogenesis might play a compensatory role in glucose transport.

  5. Consumption of synbiotic bread decreases triacylglycerol and VLDL levels while increasing HDL levels in serum from patients with type-2 diabetes.

    Science.gov (United States)

    Shakeri, Hossein; Hadaegh, Haleh; Abedi, Fatemeh; Tajabadi-Ebrahimi, Maryam; Mazroii, Navid; Ghandi, Yaser; Asemi, Zatollah

    2014-07-01

    To our knowledge, no reports are available indicating the favorable effects of synbiotic bread consumption on blood lipid profiles among patients with type 2 diabetes mellitus (T2DM). This study was conducted to evaluate the effects of the daily consumption of synbiotic bread on blood lipid profiles of patients with T2DM. This randomized double-blinded controlled clinical trial was performed with 78 diabetic patients, aged 35-70 years. After a 2-week run-in period, subjects were randomly assigned to consume either synbiotic (n = 26), probiotic (n = 26) or control bread (n = 26) for 8 weeks. The synbiotic bread contained viable and heat-resistant probiotic Lactobacillus sporogenes (1 × 10(8) CFU) and 0.07 g inulin (HPX) as prebiotic per 1 g. The probiotic bread contained L. sporogenes (1 × 10(8) CFU) per 1 g. Patients were asked to consume the synbiotic, probiotic and control breads three times a day in a 40 g package for a total of 120 g/day. Biochemical measurements including blood lipid profiles were conducted before and after 8 weeks of intervention. Consumption of the synbiotic bread, compared to the probiotic and control breads, led to a significant decrease in serum TAG (P = 0.005), VLDL-C (P = 0.005), TC/HDL-C (P = 0.002) and a significant increase in serum HDL-C levels (P = 0.01). No significant effect of synbiotic bread consumption on FPG, TC, LDL-C and non-HDL-C levels was seen compared to the probiotic and control breads (P > 0.05). Trial registry code: http://www.irct.ir IRCT201311215623N13.

  6. Effect of insulin, the glutathione system, and superoxide anion radical in modulation of lipolysis in adipocytes of rats with experimental diabetes.

    Science.gov (United States)

    Ivanov, V V; Shakhristova, E V; Stepovaya, E A; Nosareva, O L; Fedorova, T S; Ryazantseva, N V; Novitsky, V V

    2015-01-01

    Spontaneous lipolysis was found to be increased in adipocytes of rats with alloxan-induced diabetes. In addition, isoproterenol-stimulated hydrolysis of triacylglycerols was inhibited against the background of oxidative stress and decreased redox-status of cells. A decrease in the ability of insulin to inhibit isoproterenol-stimulated lipolysis in adipocytes that were isolated from adipose tissue of rats with experimental diabetes was found, which shows a disorder in regulation of lipolysis in adipocytes by the hormone in alloxan-induced diabetes. Based on these findings, we concluded that there is an influence of reactive oxygen species, superoxide anion radical in particular, and redox potential of the glutathione system on molecular mechanisms of change in lipolysis intensity in rat adipocytes in alloxan-induced oxidative stress. Activation of spontaneous lipolysis under conditions of oxidative stress might be a reason for the high concentration of free fatty acids in blood plasma in experimental diabetes, and this may play a significant role in development of insulin resistance and appearance of complications of diabetes.

  7. Dietary conjugated linoleic acid induces lipolysis in adipose tissue of coconut oil-fed mice but not soy oil-fed mice.

    Science.gov (United States)

    Ippagunta, S; Hadenfeldt, T J; Miner, J L; Hargrave-Barnes, K M

    2011-09-01

    Mice fed diets containing conjugated linoleic acid (CLA) are leaner than mice not fed CLA. This anti-obesity effect is amplified in mice fed coconut oil-containing or fat free diets, compared to soy oil diets. The present objective was to determine if CLA alters lipolysis in mice fed different base oils. Mice were fed diets containing soy oil (SO), coconut oil (CO), or fat free (FF) for 6 weeks, followed by 10 or 12 days of CLA or no CLA supplementation. Body fat, tissue weights, and ex vivo lipolysis were determined. Relative protein abundance and activation of perilipin, hormone sensitive lipase (HSL), adipose triglyceride lipase (ATGL), and adipose differentiation related protein (ADRP) were determined by western blotting. CLA feeding caused mice to have less (P oil source, P oil source interaction on lipolysis as CO + CLA and FF + CLA-fed mice had increased (P < 0.05) rates of lipolysis but SO + CLA-fed mice did not. However, after 12 days of CLA consumption, activated perilipin was increased (P < 0.05) only in SO + CLA-fed mice and total HSL and ATGL were decreased (P < 0.05) in CO + CLA-fed mice. Therefore, the enhanced CLA-induced body fat loss in CO and FF-fed mice appears to involve increased lipolysis but this effect may be decreasing by 12 days of CLA consumption.

  8. Modulation of VLDL triglyceride metabolism

    NARCIS (Netherlands)

    Bijland, Silvia

    2010-01-01

    Obesity is characterized by excessive fat storage and is associated with various diseases like cardiovascular disease (CVD) and type 2 diabetes (DM2), thereby being a serious problem of public health. Excessive energy intake is an important cause of obesity since excess energy is primarily stored as

  9. Modulation of VLDL triglyceride metabolism

    NARCIS (Netherlands)

    Bijland, Silvia

    2010-01-01

    Obesity is characterized by excessive fat storage and is associated with various diseases like cardiovascular disease (CVD) and type 2 diabetes (DM2), thereby being a serious problem of public health. Excessive energy intake is an important cause of obesity since excess energy is primarily stored as

  10. Influence of lipolysis and ketogenesis to metabolic and hematological parameters in dairy cows during periparturient period

    Directory of Open Access Journals (Sweden)

    Cincović R.M.

    2012-01-01

    Full Text Available The aim of this study was to examine the characteristics of the metabolic profile and complete blood count in cows in the periparturient period on the basis of the intensity of lipolysis and ketogenesis (concentration of non esterified fatty acid - NEFA and betahydroxybutyrate - BHB. Based on median values of NEFA and BHB cows were divided into 3 groups: cows physiologically burdened with catabolism (NEFA and BHB levels above the median one week after parturition, cows significantly burdened with catabolism (NEFA and BHB levels above the median one week before and after parturition and cows that are not burdened with catabolism (NEFA and BHB below the median, i.e. the control group. The median value of NEFA was 0.27 mmol/L one week before parturition and 0.61 mmol/L one week after it. The median value of BHB was 0.51 mmol/L one week before parturition and 0.99 mmol/L one week after it. A significant group effect was shown for each week separately, so that cows physiologically burdened with catabolism and/or cows significantly burdened with catabolism compared to the control group have the following features of the metabolic profile and complete blood count: higher concentrations of NEFA and BHB (weeks: -1, 1, 2, 4, 8, lower concentrations of glucose (weeks: 1, 4, lower concentration of cholesterol (week 8, lower concentrations of total protein (weeks: 1, 2, lower concentrations of urea (weeks: 1, 2, 4, 8 and a higher concentration of bilirubin (weeks: - 1, 1, 2, 4, 8, increased levels of AST (weeks: -1, 1 and ALT (weeks: -1, 2, lower value of Ca (week -1, lower hemoglobin concentration (week -1, lower white blood cell count (week 4, a larger number of neutrophils (weeks: -1, 1, 2 and a higher number of lymphocytes (week 4. Using the method of factor analysis and principal components showed that NEFA, BHB and glucose are the major components that affect the metabolic profile and blood count, making 71.8% of the variability of all parameters. Cows

  11. Chronic TNFalpha and cAMP pre-treatment of human adipocytes alter HSL, ATGL and perilipin to regulate basal and stimulated lipolysis.

    Science.gov (United States)

    Bézaire, Véronic; Mairal, Aline; Anesia, Rodica; Lefort, Corinne; Langin, Dominique

    2009-09-17

    We examined the effects of chronic TNFalpha and dibutyryl-cAMP (Db-cAMP) pre-treatment on the lipolytic machinery of human hMADS adipocytes. TNFalpha decreased adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein content and triglycerides (TG)-hydrolase activity but increased basal lipolysis due to a marked reduction in perilipin (PLIN) protein content. Conversely, Db-cAMP increased ATGL and HSL protein content but prevented PLIN phosphorylation, the net result being accentuated basal lipolysis. In forskolin-stimulated conditions, TNFalpha and Db-cAMP pre-treatment decreased stimulated TG-hydrolase activity and impaired PLIN phosphorylation. Together, this resulted in a severely attenuated response to forskolin-stimulated lipolysis.

  12. Laser-assisted lipolysis for cankle remodelling: a prospective study in 30 patients.

    Science.gov (United States)

    Leclère, Franck Marie; Moreno-Moraga, Javier; Mordon, Serge; Servell, Pascal; Unglaub, Frank; Kolb, Frédéric; Rimareix, Françoise; Trelles, Mario A

    2014-01-01

    Cankles refer to the area where the calf and ankle meet. Unaesthetic fat cankles, where definition between the calf and ankle is impossible, are a frustrating aesthetic deformity, which are exacerbated by their genetic conditioning and special resistance to diet. This article reports our experience with laser-assisted lipolysis (LAL) in cankle remodelling. A total of 30 patients were treated for unaesthetic fat cankles with LAL. The 924/975-nm diode laser used in this study consisted of two lasers, one emitting at 924 nm, and the other at 975 nm. According to our mathematical models, we assumed that to destroy 1 ml of fat, 0.1 kJ was required in dual emission mode at 924/975 nm. Patients were asked to file a satisfaction questionnaire. Ultrasound was used to measure the fat thickness pre- and postoperatively. Oedema in both lateral sulcus of the Achilles tendon was seen in all patients. It subsided after 4 weeks in nine cases and 6 weeks in 21 cases. Only two patients developed mild hyperpigmentation that disappeared, respectively, after 4 and 10 weeks. Pain during the anaesthesia and discomfort after the procedure were low with this technique. Mean down time was 1.0 day. Of the 30 patients, 29 would recommend this treatment. Overall, high patient and investigator satisfaction was confirmed by the sonography used to measure decrease in fat thickness. LAL in cankle remodelling is a safe and reproducible technique that is particularly appreciated by the patient. The procedure allows homogenous reduction of fatty tissue together with skin tightening.

  13. Survival response to increased ceramide involves metabolic adaptation through novel regulators of glycolysis and lipolysis.

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    Niraj K Nirala

    2013-06-01

    Full Text Available The sphingolipid ceramide elicits several stress responses, however, organisms survive despite increased ceramide but how they do so is poorly understood. We demonstrate here that the AKT/FOXO pathway regulates survival in increased ceramide environment by metabolic adaptation involving changes in glycolysis and lipolysis through novel downstream targets. We show that ceramide kinase mutants accumulate ceramide and this leads to reduction in energy levels due to compromised oxidative phosphorylation. Mutants show increased activation of Akt and a consequent decrease in FOXO levels. These changes lead to enhanced glycolysis by upregulating the activity of phosphoglyceromutase, enolase, pyruvate kinase, and lactate dehydrogenase to provide energy. A second major consequence of AKT/FOXO reprogramming in the mutants is the increased mobilization of lipid from the gut through novel lipase targets, CG8093 and CG6277 for energy contribution. Ubiquitous reduction of these targets by knockdown experiments results in semi or total lethality of the mutants, demonstrating the importance of activating them. The efficiency of these adaptive mechanisms decreases with age and leads to reduction in adult life span of the mutants. In particular, mutants develop cardiac dysfunction with age, likely reflecting the high energy requirement of a well-functioning heart. The lipases also regulate physiological triacylglycerol homeostasis and are important for energy metabolism since midgut specific reduction of them in wild type flies results in increased sensitivity to starvation and accumulation of triglycerides leading to cardiac defects. The central findings of increased AKT activation, decreased FOXO level and activation of phosphoglyceromutase and pyruvate kinase are also observed in mice heterozygous for ceramide transfer protein suggesting a conserved role of this pathway in mammals. These data reveal novel glycolytic and non-autonomous lipolytic pathways in

  14. The Evaluation of Efficacy of the Combination of Acoustic Cavitation and Radiofrequency Lipolysis in Body Sculpturing

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    Seval Dogruk Kacar

    2014-02-01

    Full Text Available Aim: There is widespread use of noninvasive body sculpturing methods with the emerging new technologies in the field of aesthethic dermatology. However scientific data about these methods is limited. In our study the efficacy of the combination of acoustic cavitation and radiofrequency in body sculpturing is retrospectively evaluated. Material and Method: We retrospectively evaluated the patients who underwent body contouring treatment for belly and waist area in Dermatocosmetology unit of Afyon Kocatepe University Hospital between September 2012 and September 2013. The combination of acoustic cavitation and radiofrequency is applied 2 times a week for 10 sessions for body contouring of waist and belly. Before treatment and after each session the height, weight and perimetric measurements are recorded. Patients satisfaction level is assessed by visual analogue scale (VAS between 0 (dissatisfied, no effect and 5 (very satisfied, very effective. Results: The mean age of 15 female patients were 36,4±10,2 (23-52. There were statistically significant difference in weight and perimetric measurements of waist (superior waist, waist circumference, inferior waist between the beginning and end of treatment (respectively, p=0.002 and p=0.001 for the remaining three. Sixty percent of patients described the treatment as satisfactory according to VAS. The remaining were not satisfied although the treatments produced a change. No adverse effects reported other than a transient erythema during treatment. Discussion: Diet and exercise are still the most relevant ways to achieve optimal body shape and tone. Besides it is possible to eliminate excess fat and skin in appropriate patients by body sculpturing methods such as invasive and noninvasive liposuction and lipolysis. We found the combination of acoustic cavitation and radiofrequency effective in body shaping.

  15. Lack of plasma albumin impairs intravascular lipolysis and explains the associated free fatty acids deficiency and hypertriglyceridemia

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    Oliveira Helena CF

    2010-12-01

    Full Text Available Abstract Background Abnormalities in lipid metabolism and transport are hallmarks in analbuminemic Nagase rats (NAR and humans. Triglyceridemia is nearly 3- to 5-fold higher in female NAR than in control Sprague-Dawley rats (SDR. Also, NAR present with a severe plasma free fatty acid (FFA deficit. There are conflicting results regarding the mechanisms underlying NAR hypertriglyceridemia. Objective We aimed at investigating whether liver lipogenesis and triglyceride secretion rates into the plasma contribute to the hypertriglyceridemia in NAR. We also studied whether heparin or albumin administration would release the hypothesized lipolysis inhibition in NAR. Methods The incorporation of tritiated water into lipids and the linear accumulation rate of plasma triglycerides after Triton WR1339 injection were the measures of liver lipogenesis and triglyceride secretion rates. Results Lipogenesis (596 ± 40 vs. 929 ± 124 μmol 3H2O/g/h and triglyceride (4.25 ± 1.00 vs. 7.04 ± 1.68 mg/dL/min secretion rates were slower (P ≤ 0.05 in fasted NAR than in control SDR. The injection of either heparin or albumin elicited an increase in NAR plasma FFA levels over time. FFA levels reached control levels 90 min after the albumin administration, increasing from 0.36 ± 0.05 to 1.34 ± 0.16 mEq/L (P ≤ 0.05. These results indicate that the lack of plasma albumin inhibits intravascular lipolysis and causes the FFA deficit observed in NAR. Conclusion NAR hepatic triglyceride synthesis and output do not contribute to NAR hypertriglyceridemia. We propose that the lack of albumin diminishes intravascular lipolysis which reduces the plasma triglyceride removal rate and explain both NAR hypertriglyceridemia and FFA deficiency.

  16. Higher levels of ATGL are associated with exercise-induced enhancement of lipolysis in rat epididymal adipocytes.

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    Junetsu Ogasawara

    Full Text Available BACKGROUND: In adipose cells, adipose triglyceride lipase (ATGL catalyzes the first step in adipocyte triacylglyceride hydrolysis, thereby regulating both basal and hormone-stimulated lipolysis. However, little is known about the molecular mechanism(s underlying habitual exercise-induced adaptive modulation of ATGL in white adipocytes via alteration in transcription regulator and lipolytic cofactors. METHODOLOGY/PRINCIPAL RESULTS: Male Wistar rats were randomly divided into 2 groups a sedentary control group (CG and a habitual exercise group (EG. The EG was subjected to running on a treadmill set at 5 days per week for 9 weeks. The CG was not subjected to running on a treadmill. In the EG, levels of ATGL mRNA and protein were elevated with a significant increase in lipolysis compared with the CG, accompanied by a significant increase in associations of CGI-58 with ATGL protein. Under these conditions, an upregulation of peroxisome proliferation-activated receptorg-2 (PPARg-2 was observed. In the EG, the addition of rosiglitazone further significantly increased the levels of ATGL protein compared with the CG. However, attenuated levels of the ATGL protein in adipocytes were obtained by the addition of insulin, which is known to inhibit the expression of ATGL, in both types of groups. Actually, levels of plasma insulin were significantly reduced in the EG compared with the CG. CONCLUSIONS: These data suggest that elevated levels of ATGL are involved in the exercise-induced enhancement of lipolysis in primary adipocytes. The exact mechanism(s underlying this phenomenon is associated, at least in part, with upregulated transcriptional activation of PPARg-2. In addition, exercise-induced lower circulation levels of insulin also correlate with habitual exercise-induced higher levels of ATGL in primary adipocytes.

  17. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Directory of Open Access Journals (Sweden)

    Amandine Girousse

    Full Text Available When energy is needed, white adipose tissue (WAT provides fatty acids (FAs for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  18. Partial Inhibition of Adipose Tissue Lipolysis Improves Glucose Metabolism and Insulin Sensitivity Without Alteration of Fat Mass

    Science.gov (United States)

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet–fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity. PMID:23431266

  19. Widdrol-induced lipolysis is mediated by PKC and MEK/ERK in 3T3-L1 adipocytes.

    Science.gov (United States)

    Jeong, Hyun Young; Yun, Hee Jung; Kim, Byung Woo; Lee, Eun Woo; Kwon, Hyun Ju

    2015-12-01

    Obesity is a serious medical condition causing various diseases such as heart disease, type-2 diabetes, and cancer. Fat cells (adipocytes) play an important role in the generation of energy through hydrolysis of lipids they accumulate. Therefore, induction of lipolysis (breakdown of lipids into fatty acids and glycerol), is one of the ways to treat obesity. In the present study, we investigated the lipolytic effect of widdrol in 3T3-L1 adipocytes and its mechanism. Widdrol considerably increased the amount of glycerol released from 3T3-L1 adipocytes into the medium in a time- and dose-dependent manner. To determine the mechanism of this effect, we investigated the alterations in glycerol release and protein expression in 3T3-L1 adipocytes treated with widdrol alone or widdrol and inhibitors of proteins involved in the cAMP-dependent pathway or cAMP-independent PKC-MAPK pathway, which are known to induce lipolysis in adipocytes. The adenylyl cyclase inhibitor SQ-22536, PLA2 inhibitor dexamethasone, PI3K inhibitor wortmannin, and PKA inhibitor H-89, which were used to investigate the involvement of the cAMP-dependent pathway, did not affect the lipolytic effect of widdrol. Widdrol-induced phosphorylation of PKC, MEK, and ERK, which are related to the PKC-MAPK pathway, and their phosphorylation was inhibited by their inhibitors (H-7, U0126, and PD-98059, respectively). Moreover, the increase in glycerol release induced by widdrol was almost completely blocked by PKC, MEK, and ERK inhibitors. These results suggest that widdrol induces lipolysis through activation of the PKC-MEK-ERK pathway.

  20. Green tea catechins enhance norepinephrine-induced lipolysis via a protein kinase A-dependent pathway in adipocytes.

    Science.gov (United States)

    Chen, Shu; Osaki, Noriko; Shimotoyodome, Akira

    2015-05-22

    Green tea catechins have been shown to attenuate obesity in animals and humans. The catechins activate adenosine monophosphate-activated protein kinase (AMPK), and thereby increase fatty acid oxidation in liver and skeletal muscles. Green tea catechins have also been shown to reduce body fat in humans. However, the effect of the catechins on lipolysis in adipose tissue has not been fully understood. The aim of this study was to clarify the effect of green tea catechins on lipolysis in adipocytes and to elucidate the underlying mechanism. Differentiated mouse adipocyte cell line (3T3-L1) was stimulated with green tea catechins in the presence or absence of norepinephrine. Glycerol and free fatty acids in the media were measured. Phosphorylation of hormone-sensitive lipase (HSL) was determined by Western blotting, and the mRNA expression levels of HSL, adipose triglyceride lipase (ATGL), and perilipin were determined by quantitative RT-PCR. The cells were treated with inhibitors of protein kinase A (PKA), protein kinase C (PKC), protein kinase G (PKG), or mitogen-activated protein kinase (MAPK) to determine the responsible pathway. Treatment of 3T3-L1 adipocytes with green tea catechins increased the level of glycerol and free fatty acids released into the media in the presence, but not absence, of norepinephrine, and increased the level of phosphorylated HSL in the cells. The catechins also increased mRNA and protein levels of HSL and ATGL. PKA inhibitor (H89) attenuated the catechin-induced increase in glycerol release and HSL phosphorylation. The results demonstrate that green tea catechins enhance lipolysis in the presence of norepinephrine via a PKA-dependent pathway in 3T3-L1 adipocytes, providing a potential mechanism by which green tea catechins could reduce body fat.

  1. Partial inhibition of adipose tissue lipolysis improves glucose metabolism and insulin sensitivity without alteration of fat mass.

    Science.gov (United States)

    Girousse, Amandine; Tavernier, Geneviève; Valle, Carine; Moro, Cedric; Mejhert, Niklas; Dinel, Anne-Laure; Houssier, Marianne; Roussel, Balbine; Besse-Patin, Aurèle; Combes, Marion; Mir, Lucile; Monbrun, Laurent; Bézaire, Véronic; Prunet-Marcassus, Bénédicte; Waget, Aurélie; Vila, Isabelle; Caspar-Bauguil, Sylvie; Louche, Katie; Marques, Marie-Adeline; Mairal, Aline; Renoud, Marie-Laure; Galitzky, Jean; Holm, Cecilia; Mouisel, Etienne; Thalamas, Claire; Viguerie, Nathalie; Sulpice, Thierry; Burcelin, Rémy; Arner, Peter; Langin, Dominique

    2013-01-01

    When energy is needed, white adipose tissue (WAT) provides fatty acids (FAs) for use in peripheral tissues via stimulation of fat cell lipolysis. FAs have been postulated to play a critical role in the development of obesity-induced insulin resistance, a major risk factor for diabetes and cardiovascular disease. However, whether and how chronic inhibition of fat mobilization from WAT modulates insulin sensitivity remains elusive. Hormone-sensitive lipase (HSL) participates in the breakdown of WAT triacylglycerol into FAs. HSL haploinsufficiency and treatment with a HSL inhibitor resulted in improvement of insulin tolerance without impact on body weight, fat mass, and WAT inflammation in high-fat-diet-fed mice. In vivo palmitate turnover analysis revealed that blunted lipolytic capacity is associated with diminution in FA uptake and storage in peripheral tissues of obese HSL haploinsufficient mice. The reduction in FA turnover was accompanied by an improvement of glucose metabolism with a shift in respiratory quotient, increase of glucose uptake in WAT and skeletal muscle, and enhancement of de novo lipogenesis and insulin signalling in liver. In human adipocytes, HSL gene silencing led to improved insulin-stimulated glucose uptake, resulting in increased de novo lipogenesis and activation of cognate gene expression. In clinical studies, WAT lipolytic rate was positively and negatively correlated with indexes of insulin resistance and WAT de novo lipogenesis gene expression, respectively. In obese individuals, chronic inhibition of lipolysis resulted in induction of WAT de novo lipogenesis gene expression. Thus, reduction in WAT lipolysis reshapes FA fluxes without increase of fat mass and improves glucose metabolism through cell-autonomous induction of fat cell de novo lipogenesis, which contributes to improved insulin sensitivity.

  2. Histologic evaluation of laser lipolysis comparing continuous wave vs pulsed lasers in an in vivo pig model.

    Science.gov (United States)

    Levi, Jessica R; Veerappan, Anna; Chen, Bo; Mirkov, Mirko; Sierra, Ray; Spiegel, Jeffrey H

    2011-01-01

    To evaluate acute and delayed laser effects of subdermal lipolysis and collagen deposition using an in vivo pig model and to compare histologic findings in fatty tissue after continuous wave diode (CW) vs pulsed laser treatment. Three CW lasers (980, 1370, and 1470 nm) and 3 pulsed lasers (1064, 1320, and 1440 nm) were used to treat 4 Göttingen minipigs. Following administration of Klein tumescent solution, a laser cannula was inserted at the top of a 10 × 2.5-cm rectangle and was passed subdermally to create separate laser "tunnels." Temperatures at the surface and at intervals of 4-mm to 20-mm depths were recorded immediately after exposure and were correlated with skin injury. Full-thickness cutaneous biopsy specimens were obtained at 1 day, 1 week, and 1 month after exposure and were stained with hematoxylin-eosin and trichrome stain. Qualitative and semiquantitative histopathologic evaluations were performed with attention to vascular damage, lipolysis, and collagen deposition. Skin surface damage occurred at temperatures exceeding 46°C. Histologic examination at 1 day after exposure showed hemorrhage, fibrous collagen fiber coagulation, and adipocyte damage. Adipocytes surrounded by histiocytes, a marker of lipolysis, were present at 1 week and 1 month after exposure. Collagen deposition in subdermal fatty tissue and in reticular dermis of some specimens was noted at 1 week and had increased at 1 month. Tissue treated with CW laser at 1470 nm demonstrated greater hemorrhage and more histiocytes at damage sites than tissue treated with pulsed laser at 1440 nm. There was a trend toward more collagen deposition with pulsed lasers than with CW lasers, but this was not statistically significant. Histopathologic comparison between results of CW laser at 980 nm vs pulsed laser at 1064 nm showed the same trend. Hemorrhage differences may result from pulse duration variations. A theoretical calculation estimating temperature rise in vessels supported this

  3. Activation of alpha2-adrenergic receptors blunts epinephrine-induced lipolysis in subcutaneous adipose tissue during a hyperinsulinemic euglycemic clamp in men.

    Science.gov (United States)

    Stich, Vladimir; Pelikanova, Tereza; Wohl, Petr; Sengenès, Coralie; Zakaroff-Girard, Alexia; Lafontan, Max; Berlan, Michel

    2003-09-01

    The aim of this study was to investigate whether hyperinsulinemia modifies adrenergic control of lipolysis, with particular attention paid to the involvement of antilipolytic alpha2-adrenergic receptors (AR). Eight healthy male subjects (age: 23.9 +/- 0.9 yr; body mass index: 23.8 +/- 1.9) were investigated during a 6-h euglycemichyperinsulinemic clamp and in control conditions. Before and during the clamp, the effect of graded perfusions of isoproterenol (0.1 and 1 microM) or epinephrine (1 and 10 microM) on the extracellular glycerol concentration in subcutaneous abdominal adipose tissue was evaluated by using the microdialysis method. Both isoproterenol and epinephrine induced a dose-dependent increase in extracellular glycerol concentration when infused for 60 min through the microdialysis probes before and during hours 3 and 6 of the clamp. The catecholamine-induced increase was significantly lower during the clamp than before it, with the inhibition being more pronounced in hour 6 of the clamp. Isoproterenol (1 microM)-induced lipolysis was reduced by 28 and 44% during hours 3 and 6 of the clamp, respectively, whereas the reduction of epinephrine (100 microM)-induced lipolysis was significantly greater (by 63 and 70%, P < 0.01 and P < 0.04, respectively) during the same time intervals. When epinephrine was infused in combination with 100 microM phentolamine (a nonselective alpha-AR antagonist), the inhibition of epinephrine (10 microM)-induced lipolysis was only of 19 and 40% during hours 3 and 6 of the clamp, respectively. The results demonstrate that, in situ, insulin counteracts the epinephrine-induced lipolysis in adipose tissue. The effect involves 1) reduction of lipolysis stimulation mediated by the beta-adrenergic pathway and 2) the antilipolytic component of epinephrine action mediated by alpha2-ARs.

  4. Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK.

    Science.gov (United States)

    Gaidhu, Mandeep P; Anthony, Nicole M; Patel, Prital; Hawke, Thomas J; Ceddia, Rolando B

    2010-04-01

    This study investigated the molecular mechanisms by which a high-fat diet (HFD) dysregulates lipolysis and lipid metabolism in mouse epididymal (visceral, VC) and inguinal (subcutaneous, SC) adipocytes. Eight-weeks of HFD feeding increased adipose triglyceride lipase (ATGL) content and comparative gene identification-58 (CGI-58) expression, whereas hormone-sensitive lipase (HSL) phosphorylation and perilipin content were severely reduced. Adipocytes from HFD mice elicited increased basal but blunted epinephrine-stimulated lipolysis and increased diacylglycerol content in both fat depots. Consistent with impaired adrenergic receptor signaling, HFD also increased adipose-specific phospholipase A(2) expression in both fat depots. Inhibition of E-prostanoid 3 receptor increased basal lipolysis in control adipocytes but failed to acutely alter the effects of HFD on lipolysis in both fat depots. In HFD visceral adipocytes, activation of adenylyl cyclases by forskolin increased HSL phosphorylation and surpassed the lipolytic response of control cells. However, in HFD subcutaneous adipocytes, forskolin induced lipolysis without detectable HSL phosphorylation, suggesting activation of an alternative lipase in response to HFD-induced suppression of HSL in VC and SC adipocytes. HFD also powerfully inhibited basal, epinephrine-, and forskolin-induced AMP kinase (AMPK) activation as well peroxisome proliferator-activated receptor gamma coactivator-1alpha expression, citrate synthase activity, and palmitate oxidation in both fat depots. In summary, novel evidence is provided that defective adrenergic receptor signaling combined with upregulation of ATGL and suppression of HSL and AMPK signaling mediate HFD-induced alterations in lipolysis and lipid utilization in VC and SC adipocytes, which may play an important role in defective lipid mobilization and metabolism seen in diet-induced obesity.

  5. Evaluation of lipolysis and volatile compounds produced by three Penicillium roqueforti commercial cultures in a blue-type cheese made from ovine milk

    Directory of Open Access Journals (Sweden)

    E. Salvatore

    2015-12-01

    Full Text Available The aim of this work was to compare the effect of three different Penicillium roqueforti commercial cultures (named PS1, PS2 and PS3 on proteolysis, lipolysis and volatile flavour profile of a blue cheese made from ovine milk and lamb paste rennet. Proteolytic parameters were not significantly affected by the Penicillium roqueforti culture, while cheeses manufactured using PS2 and PS3 cultures showed the higher amount of free fatty acids (FFA and volatile FFA when compared with PS1 culture after 30 days of ripening. This study can provide important information for obtainingthe desired extent of lipolysis in this type of blue cheese.

  6. Progesterone-induced down-regulation of hormone sensitive lipase (Lipe) and up-regulation of G0/G1 switch 2 (G0s2) genes expression in inguinal adipose tissue of female rats is reflected by diminished rate of lipolysis.

    Science.gov (United States)

    Stelmanska, Ewa; Szrok, Sylwia; Swierczynski, Julian

    2015-03-01

    Decreased lipolytic activity in adipose tissue may be one of the reasons behind excess accumulation of body fat during pregnancy. The aim of this study was to analyze the effect of progesterone on the expression of: (a) Lipe (encoding hormone-sensitive lipase, HSL), (b) Pnpla2 (encoding adipose triglyceride lipase, ATGL), (c) abhydrolase domain containing 5 (Abhd5), and (d) G0/G1 switch 2 (G0s2) genes in white adipose tissue (WAT), as potential targets for progesterone action during the course of pregnancy. Administration of progesterone to female rats, which was reflected by approximately 2.5-fold increase in circulating progesterone concentration, is associated with a decrease in Lipe gene expression in the inguinal WAT. The expression of Pnpla2 gene in all main fat depots of females and males remained unchanged after progesterone administration. Administration of progesterone resulted in an increase in the expression of Abhd5 gene (whose product increases ATGL activity) and G0s2 gene (whose product decreases ATGL activity) in the inguinal WAT of female rats. Mifepristone, a selective antagonist of progesterone receptor, abolished the effect of progesterone on Lipe, Abhd5 and G0s2 genes expression in the inguinal WAT. The decrease in Lipe and the increase in Abhd5 and G0s2 genes expression was associated with lower rate of stimulated lipolysis. Administration of progesterone exerted no effect on Lipe, Abhd5 and G0s2 genes expression and stimulated lipolysis in the retroperitoneal WAT of females, as well as in the inguinal, epididymal and retroperitoneal WAT of males. In conclusion, our findings suggest that progesterone decreases the rate of lipolysis in the inguinal WAT of female rats, inhibiting the activity of both ATGL (by stimulating synthesis of G0S2 - specific inhibitor of the enzyme) and HSL (due to inhibition of Lipe gene expression). Copyright © 2014. Published by Elsevier Ltd.

  7. Acetylshikonin from Zicao Prevents Obesity in Rats on a High-Fat Diet by Inhibiting Lipid Accumulation and Inducing Lipolysis.

    Directory of Open Access Journals (Sweden)

    Meiling Su

    Full Text Available Various drugs have been developed to treat obesity, but these have undesirable secondary effects, and an efficient but non-toxic anti-obesity drug from natural sources is desired. This study investigated the anti-obesity effects and mechanisms of action of acetylshikonin (AS-which is used in traditional Chinese medicine-in rats on a high-fat diet (HFD. Rats were fed a normal diet or an HFD; the latter group was received no treatment or were treated with 100, 300, or 900 mg/kg AS extract by intragastric administration for 6 weeks. In addition, 3T3-L1 adipocytes were treated with AS and the effects on adipogenesis and lipolysis were evaluated by western blot analysis of adipogenic transcription factors and lipid-metabolizing enzyme levels and the phosphorylation status of protein kinase (PK A and hormone-sensitive lipase (HSL. AS prevented HFD-induced obesity including reduction in body weight, white adipose tissue content, liver mass, and serum triglyceride and free fatty acid levels in rats. It also suppressed the expression of adipogenic differentiation transcription factors and decreased the expression of the adipocyte-specific proteins HSL and adipose triglyceride lipase (ATGL. Furthermore, AS treatment induced lipolysis, leading to the release of glycerol and increased in PKA and HSL phosphorylation. These findings demonstrate that AS has anti-obesity effects in a rat model and may be a safe treatment for obesity in humans.

  8. Simulating the digestion of lipid-based drug delivery systems (LBDDS): overview of in vitro lipolysis models.

    Science.gov (United States)

    Bolko, Katarina; Zvonar, Alenka; Gašperlin, Mirjana

    2014-01-01

    One of the greatest challenges in the pharmaceutical science is the improvement of oral bioavailability of poorly soluble drugs. Lately, one of the most attractive approaches has been formulation of lipid based drug delivery systems. However, the emerging popularity of these systems in the last decade has brought to light the need for efficient methods for their in vitro evaluation that would serve as their in vivo behaviour prediction tool. Because lipids are subject to lipid digestion and multiple absorption pathways in vivo, simple dissolution tests are not predictive enough when testing lipid based delivery systems. To assert these needs, the in vitro lipolysis model has been developed, utilizing pancreatic enzymes, bile and phospholipids in a temperature controlled chamber to simulate in vivo digestion. However, with very variable physiological conditions in gastrointestinal tract, this model has not been yet standardised and experiments vary among different laboratories. This review discusses in vivo events following oral application of lipid based delivery, in vitro lipolysis models to emulate them and their future perspectives.

  9. High-Throughput Lipolysis in 96-Well Plates for Rapid Screening of Lipid-Based Drug Delivery Systems.

    Science.gov (United States)

    Mosgaard, Mette D; Sassene, Philip J; Mu, Huiling; Rades, Thomas; Müllertz, Anette

    2017-04-01

    The high-throughput in vitro intestinal lipolysis model (HTP) applicable for rapid and low-scale screening of lipid-based drug delivery systems (LbDDSs) was optimized and adjusted as to be conducted in 96-well plates (HTP-96). Three different LbDDSs (I-III) loaded with danazol or cinnarizine were used as model systems. The distributions of cinnarizine and danazol in the aqueous and precipitated digestion phases generated during lipolysis in HTP-96 were compared with previously published data obtained from HTP. The final HTP-96 setup resulted in the same rank order as the original HTP model with regard to solubilization in the aqueous phase during digestion: LbDDS III > LbDDS II > LbDDS I for danazol and LbDDS III ≈ LbDDS II ≈ LbDDS I for cinnarizine. HTP-96 is a useful model for fast performance assessment of LbDDS in a small scale. Copyright © 2017 American Pharmacists Association®. Published by Elsevier Inc. All rights reserved.

  10. Berardinelli-Seip congenital lipodystrophy 2 regulates adipocyte lipolysis, browning, and energy balance in adult animals[S

    Science.gov (United States)

    Zhou, Hongyi; Lei, Xinnuo; Benson, Tyler; Mintz, James; Xu, Xiaojing; Harris, Ruth B.; Weintraub, Neal L.; Wang, Xiaoling; Chen, Weiqin

    2015-01-01

    Mutations in BSCL2/SEIPIN cause Berardinelli-Seip congenital lipodystrophy type 2 (BSCL2), but the mechanisms whereby Bscl2 regulates adipose tissue function are unclear. Here, we generated adipose tissue (mature) Bscl2 knockout (Ad-mKO) mice, in which Bscl2 was specifically ablated in adipocytes of adult animals, to investigate the impact of acquired Bscl2 deletion on adipose tissue function and energy balance. Ad-mKO mice displayed reduced adiposity and were protected against high fat diet-induced obesity, but not insulin resistance or hepatic steatosis. Gene expression profiling and biochemical assays revealed increased lipolysis and fatty acid oxidation in white adipose tissue (WAT) and brown adipose tissue , as well as browning of WAT, owing to induction of cAMP/protein kinase A signaling upon Bscl2 deletion. Interestingly, Bscl2 deletion reduced food intake and downregulated adipose β3-adrenergic receptor (ADRB3) expression. Impaired ADRB3 signaling partially offsets upregulated browning-induced energy expenditure and thermogenesis in Ad-mKO mice housed at ambient temperature. However, this counter-regulatory response was abrogated under thermoneutral conditions, resulting in even greater body mass loss in Ad-mKO mice. These findings suggest that Bscl2 regulates adipocyte lipolysis and β-adrenergic signaling to produce complex effects on adipose tissues and whole-body energy balance. PMID:26269358

  11. Impact of aluminum on the oxidation of lipids and enzymatic lipolysis in monomolecular films at the air/water interface.

    Science.gov (United States)

    Corvis, Yohann; Korchowiec, Beata; Brezesinski, Gerald; Follot, Sébastien; Rogalska, Ewa

    2007-03-13

    There is evidence that serious pathologies are associated with aluminum (Al). In the present work, the influence of Al on enzymatic lipolysis was studied with the aim to get more insight into the possible link between the Al-induced membrane modification and the cytotoxicity of the trivalent cation (AlIII). Lipid monolayers were used as model membranes. The monomolecular film technique allowed monitoring the Al-dependent modifications of the lipid monolayer properties and enzyme kinetics. Two enzymes, namely, Candida rugosa lipase and a calcium (CaII)-dependent phospholipase A2 from porcine pancreas, were used to catalyze the lipolysis of triglyceride and phosphoglyceride monolayers, respectively. The results obtained show that Al modifies both the monolayer structure and enzymatic reaction rates. While the enzymes used in this study can be considered as probes detecting lipid membrane properties, it cannot be excluded that in physiological conditions modulation of the enzyme action by the Al-bound membranes is among the reasons for Al toxicity.

  12. Grb10 promotes lipolysis and thermogenesis by phosphorylation-dependent feedback inhibition of mTORC1.

    Science.gov (United States)

    Liu, Meilian; Bai, Juli; He, Sijia; Villarreal, Ricardo; Hu, Derong; Zhang, Chuntao; Yang, Xin; Liang, Huiyun; Slaga, Thomas J; Yu, Yonghao; Zhou, Zhiguang; Blenis, John; Scherer, Philipp E; Dong, Lily Q; Liu, Feng

    2014-06-03

    Identification of key regulators of lipid metabolism and thermogenic functions has important therapeutic implications for the current obesity and diabetes epidemic. Here, we show that Grb10, a direct substrate of mechanistic/mammalian target of rapamycin (mTOR), is expressed highly in brown adipose tissue, and its expression in white adipose tissue is markedly induced by cold exposure. In adipocytes, mTOR-mediated phosphorylation at Ser501/503 switches the binding preference of Grb10 from the insulin receptor to raptor, leading to the dissociation of raptor from mTOR and downregulation of mTOR complex 1 (mTORC1) signaling. Fat-specific disruption of Grb10 increased mTORC1 signaling in adipose tissues, suppressed lipolysis, and reduced thermogenic function. The effects of Grb10 deficiency on lipolysis and thermogenesis were diminished by rapamycin administration in vivo. Our study has uncovered a unique feedback mechanism regulating mTORC1 signaling in adipose tissues and identified Grb10 as a key regulator of adiposity, thermogenesis, and energy expenditure. Copyright © 2014 Elsevier Inc. All rights reserved.

  13. Genetic control of ATGL-mediated lipolysis modulates adipose triglyceride stores in leptin-deficient mice[S

    Science.gov (United States)

    Marcelin, Genevieve; Liu, Shun-Mei; Li, Xiaosong; Schwartz, Gary J.; Chua, Streamson

    2012-01-01

    Dissecting the genetics of complex traits such as obesity allows the identification of causal genes for disease. Here, we show that the BALB/c mouse strain carries genetic variants that confer resistance to obesity induced by leptin-deficiency or a high-fat diet (HFD). We set out to identify the physiological and genetic bases underlying this phenotype. When compared with C57BL6/J ob/ob mice (B6), BALB/c ob/ob mice exhibited decreased food intake, increased thermogenic capacity, and improved fat catabolism, each of which can potentially modify obesity. Interestingly, analysis of F1 ob/ob (progeny of B6 ob/+ × BALB/c ob+) mice revealed that obesity resistance in BALB/c ob/ob mice principally relied upon improved fat mobilization. This was mechanistically explained by increased adipose triglyceride lipase (ATGL) content in adipocytes, along with increased lipolysis and fatty acid oxidation. We conducted a genome-wide scan and defined a quantitative trait locus (QTL) on chromosome 2. BALB/c alleles on chromosome 2 not only associated with the obesity resistance phenotype but also supported increased ATGL content in adipose tissue. In summary, our study provides evidence that leptin-independent control of adipocyte lipolysis rates directly modifies the balance of macronutrient handling and is sufficient to regulate fat mass in the absence of alterations in food intake and energy expenditure.—Marcelin, G., S-M. Liu, X. Li, G. J. Schwartz, and S. Chua. PMID:22383686

  14. Acetylshikonin from Zicao Prevents Obesity in Rats on a High-Fat Diet by Inhibiting Lipid Accumulation and Inducing Lipolysis.

    Science.gov (United States)

    Su, Meiling; Huang, Wendong; Zhu, Banghao

    2016-01-01

    Various drugs have been developed to treat obesity, but these have undesirable secondary effects, and an efficient but non-toxic anti-obesity drug from natural sources is desired. This study investigated the anti-obesity effects and mechanisms of action of acetylshikonin (AS)-which is used in traditional Chinese medicine-in rats on a high-fat diet (HFD). Rats were fed a normal diet or an HFD; the latter group was received no treatment or were treated with 100, 300, or 900 mg/kg AS extract by intragastric administration for 6 weeks. In addition, 3T3-L1 adipocytes were treated with AS and the effects on adipogenesis and lipolysis were evaluated by western blot analysis of adipogenic transcription factors and lipid-metabolizing enzyme levels and the phosphorylation status of protein kinase (PK) A and hormone-sensitive lipase (HSL). AS prevented HFD-induced obesity including reduction in body weight, white adipose tissue content, liver mass, and serum triglyceride and free fatty acid levels in rats. It also suppressed the expression of adipogenic differentiation transcription factors and decreased the expression of the adipocyte-specific proteins HSL and adipose triglyceride lipase (ATGL). Furthermore, AS treatment induced lipolysis, leading to the release of glycerol and increased in PKA and HSL phosphorylation. These findings demonstrate that AS has anti-obesity effects in a rat model and may be a safe treatment for obesity in humans.

  15. Photoactivation of Dok1/ERK/PPARγ signaling axis inhibits excessive lipolysis in insulin-resistant adipocytes.

    Science.gov (United States)

    Jiang, Xiaoxiao; Huang, Lei; Xing, Da

    2015-07-01

    Insulin resistance is a hallmark of the metabolic syndrome and type 2 diabetes. Increased plasma FFA level is an important cause of obesity-associated insulin resistance. Over-activated ERK is closely related with FFA release from adipose tissues in patients with type 2 diabetes. Nevertheless, there are no effective strategies to lower plasma FFA level. Low-power laser irradiation (LPLI) has been reported to regulate multiple biological processes. However, whether LPLI could ameliorate metabolic disorders and the molecular mechanisms involved remain unknown. In this study, we first demonstrated that LPLI suppresses excessive lipolysis of insulin-resistant adipocytes by activating tyrosine kinases-1(Dok1)/ERK/PPARγ pathway. Our data showed that LPLI inhibits ERK phosphorylation through the activation of Dok1, resulting in decreased phospho-PPARγ level. Non-phosphorylated PPARγ maintains in nucleus to promote the expression of adipogenic genes, reversing excessive lipolysis in insulin-resistant adipocytes. In summary, the present research highlights the important roles of Dok1/ERK/PPARγ pathway in lowering FFA release from adipocytes, and our research extends the knowledge of the biological effects induced by LPLI. Copyright © 2015. Published by Elsevier Inc.

  16. Impact of Reduced ATGL-Mediated Adipocyte Lipolysis on Obesity-Associated Insulin Resistance and Inflammation in Male Mice.

    Science.gov (United States)

    Schoiswohl, Gabriele; Stefanovic-Racic, Maja; Menke, Marie N; Wills, Rachel C; Surlow, Beth A; Basantani, Mahesh K; Sitnick, Mitch T; Cai, Lingzhi; Yazbeck, Cynthia F; Stolz, Donna B; Pulinilkunnil, Thomas; O'Doherty, Robert M; Kershaw, Erin E

    2015-10-01

    Emerging evidence suggests that impaired regulation of adipocyte lipolysis contributes to the proinflammatory immune cell infiltration of metabolic tissues in obesity, a process that is proposed to contribute to the development and exacerbation of insulin resistance. To test this hypothesis in vivo, we generated mice with adipocyte-specific deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme catalyzing triacylglycerol hydrolysis. In contrast to previous models, adiponectin-driven Cre expression was used for targeted ATGL deletion. The resulting adipocyte-specific ATGL knockout (AAKO) mice were then characterized for metabolic and immune phenotypes. Lean and diet-induced obese AAKO mice had reduced adipocyte lipolysis, serum lipids, systemic lipid oxidation, and expression of peroxisome proliferator-activated receptor alpha target genes in adipose tissue (AT) and liver. These changes did not increase overall body weight or fat mass in AAKO mice by 24 weeks of age, in part due to reduced expression of genes involved in lipid uptake, synthesis, and adipogenesis. Systemic glucose and insulin tolerance were improved in AAKO mice, primarily due to enhanced hepatic insulin signaling, which was accompanied by marked reduction in diet-induced hepatic steatosis as well as hepatic immune cell infiltration and activation. In contrast, although adipocyte ATGL deletion reduced AT immune cell infiltration in response to an acute lipolytic stimulus, it was not sufficient to ameliorate, and may even exacerbate, chronic inflammatory changes that occur in AT in response to diet-induced obesity.

  17. Acerola (Malpighia emarginata DC.) juice intake protects against alterations to proteins involved in inflammatory and lipolysis pathways in the adipose tissue of obese mice fed a cafeteria diet.

    Science.gov (United States)

    Dias, Fernando Milanez; Leffa, Daniela Dimer; Daumann, Francine; Marques, Schérolin de Oliveira; Luciano, Thais F; Possato, Jonathan Correa; de Santana, Aline Alves; Neves, Rodrigo Xavier; Rosa, José Cesar; Oyama, Lila Missae; Rodrigues, Bruno; de Andrade, Vanessa Moraes; de Souza, Cláudio Teodoro; de Lira, Fabio Santos

    2014-02-04

    Obesity has been studied as a metabolic and an inflammatory disease and is characterized by increases in the production of pro-inflammatory adipokines in the adipose tissue.To elucidate the effects of natural dietary components on the inflammatory and metabolic consequences of obesity, we examined the effects of unripe, ripe and industrial acerola juice (Malpighia emarginata DC.) on the relevant inflammatory and lipolysis proteins in the adipose tissue of mice with cafeteria diet-induced obesity. Two groups of male Swiss mice were fed on a standard diet (STA) or a cafeteria diet (CAF) for 13 weeks. Afterwards, the CAF-fed animals were divided into five subgroups, each of which received a different supplement for one further month (water, unripe acerola juice, ripe acerola juice, industrial acerola juice, or vitamin C) by gavage. Enzyme-linked immunosorbent assays, Western blotting, a colorimetric method and histology were utilized to assess the observed data. The CAF water (control obese) group showed a significant increase in their adiposity indices and triacylglycerol levels, in addition to a reduced IL-10/TNF-α ratio in the adipose tissue, compared with the control lean group. In contrast, acerola juice and Vitamin C intake ameliorated the weight gain, reducing the TAG levels and increasing the IL-10/TNF-α ratio in adipose tissue. In addition, acerola juice intake led to reductions both in the level of phosphorylated JNK and to increases in the phosphorylation of IκBα and HSLser660 in adipose tissue. Taken together, these results suggest that acerola juice reduces low-grade inflammation and ameliorates obesity-associated defects in the lipolytic processes.

  18. Injection of phosphatidylcholine and deoxycholic acid regulates gene expression of lipolysis-related factors, pro-inflammatory cytokines, and hormones on mouse fat tissue.

    Science.gov (United States)

    Won, Tae Joon; Nam, Yunsung; Lee, Ho Sung; Chung, Sujin; Lee, Jong Hyuk; Chung, Yoon Hee; Park, Eon Sub; Hwang, Kwang Woo; Jeong, Ji Hoon

    2013-10-01

    Injection of phosphatidylcholine (PC) and deoxycholic acid (DA) preparation is widely used as an alternative to liposuction for the reduction of subcutaneous fat. Nevertheless, its physiological effects and mechanism of action are not yet fully understood. In this report, PC and deoxycholic acid (DA) were respectively injected into adipose tissue. PC decreased tissue mass on day 7, but DA did not. On the other hand, a decrement of DNA mass was observed only in DA-injected tissue on day 7. Both PC and DA reduced the mRNA expression of adipose tissue hormones, such as adiponectin, leptin, and resistin. In lipolysis-related gene expression profiles, PC increased hormone-sensitive lipase (HSL) transcription and decreased the expression other lipases, perilipin, and the lipogenic marker peroxisome proliferator-activated receptor-γ (PPARγ); DA treatment diminished them all, including HSL. Meanwhile, the gene expression of pro-inflammatory cytokines and a chemokine was greatly elevated in both PC-injected and DA-injected adipose tissue. Microscopic observation showed that PC induced lipolysis with mild PMN infiltration on day 7. However, DA treatment did not induce lipolysis but induced much amount of PMN infiltration. In conclusion, PC alone might induce lipolysis in adipose tissue, whereas DC alone might induce tissue damage. Copyright © 2013 Elsevier Ltd. All rights reserved.

  19. Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein.

    Science.gov (United States)

    Valet, P; Berlan, M; Beauville, M; Crampes, F; Montastruc, J L; Lafontan, M

    1990-01-01

    Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition of lipolysis elicited by 2 micrograms/ml adenosine deaminase (removal of adenosine) whatever the lipolytic index used (glycerol or nonesterified fatty acids). In dog fat cells NPY and PYY inhibited adenosine deaminase-, isoproterenol- and forskolin-induced lipolysis. In humans and dogs the effects of NPY or PYY were abolished by treatment of cells with Bordetella pertussis toxin, clearly indicating the involvement of a Gi protein in the antilipolytic effects. This study indicates that, in addition to alpha 2-adrenergic agonists, NPY and PYY are also involved in the regulation of lipolysis in human and dog adipose tissue as powerful antilipolytic agents. Further studies are needed to characterize the pharmacological nature of the receptor mediating the inhibitory effect of NPY and PYY in fat cells. Images PMID:2104880

  20. Effects of plant species, stage of maturity, and level of formic acid addition on lipolysis, lipid content, and fatty acid composition during ensiling.

    Science.gov (United States)

    Koivunen, E; Jaakkola, S; Heikkilä, T; Lampi, A-M; Halmemies-Beauchet-Filleau, A; Lee, M R F; Winters, A L; Shingfield, K J; Vanhatalo, A

    2015-09-01

    Forage type and management influences the nutritional quality and fatty acid composition of ruminant milk. Replacing grass silage with red clover (RC; L.) silage increases milk fat 18:3-3 concentration. Red clover has a higher polyphenol oxidase (PPO) activity compared with grasses, which has been suggested to decrease lipolysis and . The present study characterized the abundance and fatty acid composition of esterified lipid and NEFA before and after ensiling of grass and RC to investigate the influence of forage species, growth stage, and extent of fermentation on lipolysis. A randomized block design with a 2 × 3 × 4 factorial arrangement of treatments was used. Treatments comprised RC or a mixture of timothy ( L.) and meadow fescue ( Huds.) harvested at 3 growth stages and treated with 4 levels of formic acid (0, 2, 4, and 6 L/t). Lipid in silages treated with 0 or 6 L/t formic acid were extracted and separated into 4 fractions by TLC. Total PPO activity in fresh herbage and the content of soluble bound phenols in all silages were determined. Concentrations of 18:3-3 and total fatty acids (TFA) were higher ( ensilage of RC decreases lipolysis . For both plant species, total PPO activity was not associated with the extent of lipolysis . However, bound phenols formed via PPO activity appear to have a role in protecting lipid and protein against degradation in grass and lowering proteolysis of RC during ensiling.

  1. Effects of beta-hydroxybutyrate and isoproterenol on lipolysis in isolated adipocytes from periparturient dairy cows and cows with clinical ketosis

    NARCIS (Netherlands)

    van der Drift, S. G. A.; Everts, R. R.; Houweling, M.; van Leengoed, L. A. M. G.; Stegeman, J. A.; Tielens, A. G. M.; Jorritsma, R.

    2013-01-01

    An in vitro model was used to investigate effects of beta-hydroxybutyrate and isoproterenol (beta-adrenergic receptor agonist) on lipolysis in isolated adipocytes from late pregnant and recently calved dairy cows (n = 5) and cows with clinical ketosis (n =3). Incubation with 3.0 mmol/L beta-hydroxyb

  2. Cascade regulation of PPARγ(2) and C/EBPα signaling pathways by celastrol impairs adipocyte differentiation and stimulates lipolysis in 3T3-L1 adipocytes.

    Science.gov (United States)

    Choi, Seung Kug; Park, Sunmi; Jang, Subin; Cho, Hun Hee; Lee, Siwoo; You, Seungkwon; Kim, Sang-Hyuk; Moon, Hyun-Seuk

    2016-05-01

    Celastrol, a triterpene from the root bark of the Chinese medicinal plant Tripterygium wilfordii, has been shown to exhibit anti-oxidant, anti-inflammatory, anti-cancer and insecticidal activities. Also, it has been demonstrated that celastrol has obesity-controlling effects in diet-induced obesity mice. However, direct evidence that celastrol contributes to the development of adipocyte differentiation and lipolysis has not been fully elucidated. Moreover, no previous studies have evaluated whether celastrol may regulate adipogenic transcriptional markers in adipocytes. In order to address the questions above, we extended previous observations and investigated in vitro celastrol signaling study whether celastrol may regulate differentiation, lipolysis and key adipogenic transcriptional pathways in 3T3-L1 adipocytes. Treatment of celastrol not only inhibited adipocyte differentiation (lipid accumulation, glyceraldehyde-3-phosphate dehydrogenase activity and triglyceride content) but also increased lipolysis (glycerol release and free fatty acid release) in 3T3-L1 adipocytes. In addition, all celastrol-regulated functional activities were controlled by PPARγ(2) and C/EBPα signaling pathways in duration of celastrol's treatment in 3T3-L1 adipocytes. Our initial data from in vitro celastrol signaling studies suggest novel insights into the role of PPARγ(2) and C/EBPα as probable mediators of the action of celastrol in regulating adipocyte differentiation and lipolysis in 3T3-L1 adipocytes. Copyright © 2016 Elsevier Inc. All rights reserved.

  3. ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis

    DEFF Research Database (Denmark)

    DeZwaan-McCabe, Diane; Sheldon, Ryan D; Gorecki, Michelle C

    2017-01-01

    advantage of enhanced hepatic and renal steatosis in mice lacking the ER stress sensor ATF6α. We found that impaired fatty acid oxidation contributed to the early development of steatosis in the liver but not the kidney, while anorexia-induced lipolysis promoted late triglyceride and free fatty acid...

  4. The immunosuppressive agents rapamycin, cyclosporin A and tacrolimus increase lipolysis, inhibit lipid storage and alter expression of genes involved in lipid metabolism in human adipose tissue.

    Science.gov (United States)

    Pereira, Maria J; Palming, Jenny; Rizell, Magnus; Aureliano, Manuel; Carvalho, Eugénia; Svensson, Maria K; Eriksson, Jan W

    2013-01-30

    Cyclosporin A (CsA), tacrolimus and rapamycin are immunosuppressive agents (IAs) associated with insulin resistance and dyslipidemia, although their molecular effects on lipid metabolism in adipose tissue are unknown. We explored IAs effects on lipolysis, lipid storage and expression of genes involved on lipid metabolism in isolated human adipocytes and/or adipose tissue obtained via subcutaneous and omental fat biopsies. CsA, tacrolimus and rapamycin increased isoproterenol-stimulated lipolysis and inhibited lipid storage by 20-35% and enhanced isoproterenol-stimulated hormone-sensitive lipase Ser552 phosphorylation. Rapamycin also increased basal lipolysis (~20%) and impaired insulin's antilipolytic effect. Rapamycin, down-regulated the gene expression of perilipin, sterol regulatory element-binding protein 1 (SREBP1) and lipin 1, while tacrolimus down-regulated CD36 and aP2 gene expression. All three IAs increased IL-6 gene expression and secretion, but not expression and secretion of TNF-α or adiponectin. These findings suggest that CsA, tacrolimus and rapamycin enhance lipolysis, inhibit lipid storage and expression of lipogenic genes in adipose tissue, which may contribute to the development of dyslipidemia and insulin resistance associated with immunosuppressive therapy.

  5. Inhibition of sphingolipid synthesis improves dyslipidemia in the diet-induced hamster model of insulin resistance: evidence for the role of sphingosine and sphinganine in hepatic VLDL-apoB100 overproduction.

    Science.gov (United States)

    Dekker, Mark J; Baker, Chris; Naples, Mark; Samsoondar, Josh; Zhang, Rianna; Qiu, Wei; Sacco, Jennifer; Adeli, Khosrow

    2013-05-01

    Sphingolipids have emerged as important bioactive lipid species involved in the pathogenesis of type 2 diabetes and cardiovascular disease. However, little is known of the regulatory role of sphingolipids in dyslipidemia of insulin-resistant states. We employed hamster models of dyslipidemia and insulin resistance to investigate the role of sphingolipids in hepatic VLDL overproduction, induction of insulin resistance, and inflammation. Hamsters were fed either a control chow diet, a high fructose diet, or a diet high in fat, fructose and cholesterol (FFC diet). They were then treated for 2 weeks with vehicle or 0.3 mg/kg myriocin, a potent inhibitor of de novo sphingolipid synthesis. Both fructose and FFC feeding induced significant increases in hepatic sphinganine, which was normalized to chow-fed levels with myriocin (P overproduction may be stimulated by ceramides and sphingosine and b) inhibition of sphingolipid synthesis can reduce circulating VLDL in hamsters and improve circulating lipids--an effect that is possibly due to improved insulin signaling and reduced lipogenesis but is independent of changes in inflammation.

  6. Fed and fasted state gastro-intestinal in vitro lipolysis: In vitro in vivo relations of a conventional tablet, a SNEDDS and a solidified SNEDDS.

    Science.gov (United States)

    Christophersen, Philip Carsten; Christiansen, Martin Lau; Holm, Rene; Kristensen, Jakob; Jacobsen, Jette; Abrahamsson, Bertil; Müllertz, Anette

    2014-06-16

    The present study aims at evaluating the ability of a gastro-intestinal in vitro lipolysis model to predict the performance of two lipid formulations and a conventional tablet containing a poorly soluble drug, cinnarizine, in dogs, both in the fasted and fed state. A self-nano-emulsifying drug delivery system (SNEDDS) was either dosed in a hard gelatin capsule (SNEDDS-C) or loaded onto a porous tablet core (SNEDDS-T) and compared to a marketed conventional tablet (Conv) in an in vitro lipolysis model. The model simulates the digestion in the stomach and intestine during either the fasted or the fed state. Whole fat milk (3.5%) was used in the fed state model to mimic the dynamic lipolysis events after ingestion of food. The results were compared to a dog study published in this issue. In the fasted state in vitro lipolysis model, the amount of solubilized cinnarizine decreased in the order SNEDDS-C>SNEDDS-T>Conv, which correlated well with the in vivo bioavailability. In the fed state in vitro lipolysis model, cinnarizine was solubilized to the same degree for all formulations. Compared to the fasted state model, only the performance of the conventional tablet was improved, indicating food effect. This correlated with the in vivo study, where the tablet was the only formulation with a significant food effect. The fasted state model correlated well with the in vivo results and although the fed state model did not accurately predict the fed state in vivo results, it could predict which formulation that would exhibit a food effect.

  7. Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver.

    Science.gov (United States)

    Hotta, Yuhei; Nakamura, Hirotoshi; Konishi, Morichika; Murata, Yusuke; Takagi, Hiroyuki; Matsumura, Shigenobu; Inoue, Kazuo; Fushiki, Tohru; Itoh, Nobuyuki

    2009-10-01

    Fibroblast growth factors (Fgfs) are polypeptide growth factors with diverse functions. Fgf21, a unique member of the Fgf family, is expected to function as a metabolic regulator in an endocrine manner. Hepatic Fgf21 expression was increased by fasting. The phenotypes of hepatic Fgf21 transgenic or knockdown mice and high-fat, low-carbohydrate ketogenic diet-fed mice suggests that Fgf21 stimulates lipolysis in the white adipose tissue during normal feeding and is required for ketogenesis and triglyceride clearance in the liver during fasting. However, the physiological roles of Fgf21 remain unclear. To elucidate the physiological roles of Fgf21, we generated Fgf21 knockout (KO) mice by targeted disruption. Fgf21 KO mice were viable, fertile, and seemingly normal. Food intake, oxygen consumption, and energy expenditure were also essentially unchanged in Fgf21 KO mice. However, hypertrophy of adipocytes, decreased lipolysis in adipocytes, and decreased blood nonesterified fatty acid levels were observed when Fgf21 KO mice were fed normally. In contrast, increased lipolysis in adipocytes and increased blood nonesterified fatty acid levels were observed in Fgf21 KO mice by fasting for 24 h, indicating that Fgf21 stimulates lipolysis in the white adipose tissue during feeding but inhibits it during fasting. In contrast, unexpectedly, hepatic triglyceride levels were essentially unchanged in Fgf21 KO mice. In addition, ketogenesis in Fgf21 KO mice was not impaired by fasting for 24 h. The present results indicate that Fgf21 regulates lipolysis in adipocytes in response to the metabolic state but is not required for ketogenesis and triglyceride clearance in the liver.

  8. Phospholipase C-related catalytically inactive protein (PRIP regulates lipolysis in adipose tissue by modulating the phosphorylation of hormone-sensitive lipase.

    Directory of Open Access Journals (Sweden)

    Toshiya Okumura

    Full Text Available Phosphorylation of hormone-sensitive lipase (HSL and perilipin by protein kinase A (PKA promotes the hydrolysis of lipids in adipocytes. Although activation of lipolysis by PKA has been well studied, inactivation via protein phosphatases is poorly understood. Here, we investigated whether phospholipase C-related catalytically inactive protein (PRIP, a binding partner for protein phosphatase 1 and protein phosphatase 2A (PP2A, is involved in lipolysis by regulating phosphatase activity. PRIP knockout (PRIP-KO mice displayed reduced body-fat mass as compared with wild-type mice fed with standard chow ad libitum. Most other organs appeared normal, suggesting that mutant mice had aberrant fat metabolism in adipocytes. HSL in PRIP-KO adipose tissue was highly phosphorylated compared to that in wild-type mice. Starvation of wild-type mice or stimulation of adipose tissue explants with the catabolic hormone, adrenaline, translocated both PRIP and PP2A from the cytosol to lipid droplets, but the translocation of PP2A was significantly reduced in PRIP-KO adipocytes. Consistently, the phosphatase activity associated with lipid droplet fraction in PRIP-KO adipocytes was significantly reduced and was independent of adrenaline stimulation. Lipolysis activity, as assessed by measurement of non-esterified fatty acids and glycerol, was higher in PRIP-KO adipocytes. When wild-type adipocytes were treated with a phosphatase inhibitor, they showed a high lipolysis activity at the similar level to PRIP-KO adipocytes. Collectively, these results suggest that PRIP promotes the translocation of phosphatases to lipid droplets to trigger the dephosphorylation of HSL and perilipin A, thus reducing PKA-mediated lipolysis.

  9. The neuropeptide TLQP-21 opposes obesity via C3aR1-mediated enhancement of adrenergic-induced lipolysis.

    Science.gov (United States)

    Cero, Cheryl; Razzoli, Maria; Han, Ruijun; Sahu, Bhavani Shankar; Patricelli, Jessica; Guo, ZengKui; Zaidman, Nathan A; Miles, John M; O'Grady, Scott M; Bartolomucci, Alessandro

    2017-01-01

    Obesity is characterized by excessive fat mass and is associated with serious diseases such as type 2 diabetes. Targeting excess fat mass by sustained lipolysis has been a major challenge for anti-obesity therapies due to unwanted side effects. TLQP-21, a neuropeptide encoded by the pro-peptide VGF (non-acronymic), that binds the complement 3a receptor 1 (C3aR1) on the adipocyte membrane, is emerging as a novel modulator of adipocyte functions and a potential target for obesity-associated diseases. The molecular mechanism is still largely uncharacterized. We used a combination of pharmacological and genetic gain and loss of function approaches. 3T3-L1 and mature murine adipocytes were used for in vitro experiments. Chronic in vivo experiments were conducted on diet-induced obese wild type, β1, β2, β3-adrenergic receptor (AR) deficient and C3aR1 knockout mice. Acute in vivo lipolysis experiments were conducted on Sprague Dawley rats. We demonstrated that TLQP-21 does not possess lipolytic properties per se. Rather, it enhances β-AR activation-induced lipolysis by a mechanism requiring Ca(2+) mobilization and ERK activation of Hormone Sensitive Lipase (HSL). TLQP-21 acutely potentiated isoproterenol-induced lipolysis in vivo. Finally, chronic peripheral TLQP-21 treatment decreases body weight and fat mass in diet induced obese mice by a mechanism involving β-adrenergic and C3a receptor activation without associated adverse metabolic effects. In conclusion, our data identify an alternative pathway modulating lipolysis that could be targeted to diminish fat mass in obesity without the side effects typically observed when using potent pro-lipolytic molecules.

  10. The C-terminal fibrinogen-like domain of angiopoietin-like 4 stimulates adipose tissue lipolysis and promotes energy expenditure.

    Science.gov (United States)

    McQueen, Allison E; Kanamaluru, Deepthi; Yan, Kimberly; Gray, Nora E; Wu, Leslie; Li, Mei-Lan; Chang, Anthony; Hasan, Adeeba; Stifler, Daniel; Koliwad, Suneil K; Wang, Jen-Chywan

    2017-09-29

    Angptl4 (Angiopoietin-like 4) is a circulating protein secreted by white and brown adipose tissues and the liver. Structurally, Angptl4 contains an N-terminal coiled-coil domain (CCD) connected to a C-terminal fibrinogen-like domain (FLD) via a cleavable linker, and both full-length Angptl4 and its individual domains circulate in the bloodstream. Angptl4 inhibits extracellular lipoprotein lipase (LPL) activity and stimulates the lipolysis of triacylglycerol stored by adipocytes in the white adipose tissue (WAT). The former activity is furnished by the CCD, but the Angptl4 domain responsible for stimulating adipocyte lipolysis is unknown. We show here that the purified FLD of Angptl4 is sufficient to stimulate lipolysis in mouse primary adipocytes and that increasing circulating FLD levels in mice through adenovirus-mediated overexpression (Ad-FLD) not only induces WAT lipolysis in vivo but also reduces diet-induced obesity without affecting LPL activity. Intriguingly, reduced adiposity in Ad-FLD mice was associated with increased oxygen consumption, fat utilization, and the expression of thermogenic genes (Ucp1 and Ppargc1a) in subcutaneous WAT. Moreover, Ad-FLD mice exhibited increased glucose tolerance. Chronically enhancing WAT lipolysis could produce ectopic steatosis because of an overflow of lipids from the WAT to peripheral tissues; however, this did not occur when Ad-FLD mice were fed a high-fat diet. Rather, these mice had reductions in both circulating triacylglycerol levels and the mRNA levels of lipogenic genes in the liver and skeletal muscle. We conclude that separating the FLD from the CCD-mediated LPL-inhibitory activity of full-length Angptl4 reveals lipolytic and thermogenic properties with therapeutic relevance to obesity and diabetes. © 2017 by The American Society for Biochemistry and Molecular Biology, Inc.

  11. In vitro TNF-α- and noradrenaline-stimulated lipolysis is impaired in adipocytes from growing rats fed a low-protein, high-carbohydrate diet.

    Science.gov (United States)

    Feres, Daniel D S; Dos Santos, Maísa P; Buzelle, Samyra L; Pereira, Mayara P; de França, Suélem A; Garófalo, Maria A R; Andrade, Cláudia M B; Froelich, Mendalli; de Almeida, Fhelipe J S; Frasson, Danúbia; Chaves, Valéria E; Kawashita, Nair H

    2013-08-01

    The aim of this study was to investigate tumor necrosis factor alpha (TNF-α)- and noradrenaline (NE)-stimulated lipolysis in retroperitoneal (RWAT) and epididymal (EAT) white adipose tissue as a means of understanding how low-protein, high-carbohydrate (LPHC) diet-fed rats maintain their lipid storage in a catabolic environment (marked by increases in serum TNF-α and corticosterone and sympathetic flux to RWAT and EAT), as previously observed. Adipocytes or tissues from the RWAT and EAT of rats fed an LPHC diet and rats fed a control (C) diet for 15 days were used in the experiments. The adipocytes from both tissues of the LPHC rats exhibited lower TNF-α- stimulated lipolysis compared to adipocytes from the C rats. The intracellular lipolytic agents IBMX, DBcAMPc and FSK increased lipolysis in both tissues from rats fed the C and LPHC diets compared to basal lipolysis; however, the effect was approximately 2.5-fold lower in adipocytes from LPHC rats. The LPHC diet induced a marked reduction in the β3 and α2-AR, adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) content in RWAT and EAT. The LPHC diet did not affect TNF-α receptor 1 content but did induce a reduction in ERK p44/42 in both tissues. The present work indicates that RWAT and EAT from LPHC rats have an impairment in the lipolysis signaling pathway activated by NE and TNF-α, and this impairment explains the reduced response to these lipolytic stimuli, which may be fundamental to the maintenance of lipid storage in LPHC rats.

  12. Water-in-oil microemulsions versus emulsions as carriers of hydroxytyrosol: an in vitro gastrointestinal lipolysis study using the pHstat technique.

    Science.gov (United States)

    Chatzidaki, Maria D; Mateos-Diaz, Eduardo; Leal-Calderon, Fernando; Xenakis, Aristotelis; Carrière, Frédéric

    2016-05-18

    Water-in-oil (W/O) microemulsions and emulsions based on medium chain triglycerides (MCT) were successfully formulated with the addition of emulsifiers and used as encapsulation matrices for hydroxytyrosol (HT), an antioxidant naturally found in extra virgin olive oil. The digestibility of these edible W/O dispersions by recombinant dog gastric lipase (rDGL) and porcine pancreatic lipase (PPL) was then tested at different pH values using a pHstat device. rDGL and PPL displayed a much lower activity on the W/O microemulsion than that on the W/O emulsion and MCT alone. This was explained by the presence of higher amounts of emulsifiers (4.9% w/w lecithin and monoglycerides) in the composition of W/O microemulsions compared to W/O emulsions (1.3% w/w emulsifiers). These surfactants also induced a shift of maximum lipase activity towards lower pH values, which usually reflects the competition between surfactants and lipases for binding at the lipid-water interface. rDGL and PPL were then used consecutively in a two-step digestion model mimicking the conditions found in the human gastrointestinal tract. Direct titration and back-titration of free fatty acids allowed the continuous estimation of lipolysis rates under both gastric and duodenal conditions. Gastric lipolysis of W/O microemulsions was reduced 6 to 9-fold compared to W/O emulsions. This inhibition had a major impact on the overall lipolysis, although duodenal lipolysis was less affected by the dispersion type. The presence of HT had also some minor effects on lipolysis rates.

  13. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

    Directory of Open Access Journals (Sweden)

    Verónica García-Alonso

    Full Text Available Obesity induces white adipose tissue (WAT dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES. IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1 in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16 in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of

  14. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis

    Science.gov (United States)

    García-Alonso, Verónica; Titos, Esther; Alcaraz-Quiles, Jose; Rius, Bibiana; Lopategi, Aritz; López-Vicario, Cristina; Jakobsson, Per-Johan; Delgado, Salvadora; Lozano, Juanjo; Clària, Joan

    2016-01-01

    Obesity induces white adipose tissue (WAT) dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs) are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES). IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1) in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16) in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of interactions

  15. Prostaglandin E2 Exerts Multiple Regulatory Actions on Human Obese Adipose Tissue Remodeling, Inflammation, Adaptive Thermogenesis and Lipolysis.

    Science.gov (United States)

    García-Alonso, Verónica; Titos, Esther; Alcaraz-Quiles, Jose; Rius, Bibiana; Lopategi, Aritz; López-Vicario, Cristina; Jakobsson, Per-Johan; Delgado, Salvadora; Lozano, Juanjo; Clària, Joan

    2016-01-01

    Obesity induces white adipose tissue (WAT) dysfunction characterized by unremitting inflammation and fibrosis, impaired adaptive thermogenesis and increased lipolysis. Prostaglandins (PGs) are powerful lipid mediators that influence the homeostasis of several organs and tissues. The aim of the current study was to explore the regulatory actions of PGs in human omental WAT collected from obese patients undergoing laparoscopic bariatric surgery. In addition to adipocyte hypertrophy, obese WAT showed remarkable inflammation and total and pericellular fibrosis. In this tissue, a unique molecular signature characterized by altered expression of genes involved in inflammation, fibrosis and WAT browning was identified by microarray analysis. Targeted LC-MS/MS lipidomic analysis identified increased PGE2 levels in obese fat in the context of a remarkable COX-2 induction and in the absence of changes in the expression of terminal prostaglandin E synthases (i.e. mPGES-1, mPGES-2 and cPGES). IPA analysis established PGE2 as a common top regulator of the fibrogenic/inflammatory process present in this tissue. Exogenous addition of PGE2 significantly reduced the expression of fibrogenic genes in human WAT explants and significantly down-regulated Col1α1, Col1α2 and αSMA in differentiated 3T3 adipocytes exposed to TGF-β. In addition, PGE2 inhibited the expression of inflammatory genes (i.e. IL-6 and MCP-1) in WAT explants as well as in adipocytes challenged with LPS. PGE2 anti-inflammatory actions were confirmed by microarray analysis of human pre-adipocytes incubated with this prostanoid. Moreover, PGE2 induced expression of brown markers (UCP1 and PRDM16) in WAT and adipocytes, but not in pre-adipocytes, suggesting that PGE2 might induce the trans-differentiation of adipocytes towards beige/brite cells. Finally, PGE2 inhibited isoproterenol-induced adipocyte lipolysis. Taken together, these findings identify PGE2 as a regulator of the complex network of interactions

  16. Novel method of minimally invasive removal of large lipoma after laser lipolysis with 980 nm diode laser.

    Science.gov (United States)

    Stebbins, William G; Hanke, C William; Petersen, Jeffrey

    2011-01-01

    Lipomas are the most common benign tumor of the soft tissue, often presenting as soft, mobile subcutaneous masses. These lesions are often removed for cosmetic reasons, although they may be removed secondary to considerable discomfort or paresthesias. The large majority of lipomas appear as small, solitary lesions that are best removed by surgical excision. However, surgical removal of large (>10 cm) or multiple lesions may result in significant scarring. Tumescent local anesthesia and liposuction of larger lesions has been successful in a number of cases although this technique can be hindered by overly fibrous lesions. Laser lipolysis, performed alone or before liposuction, can further facilitate removal of these lesions. This technique is a minimally invasive and effective method of lipoma removal, resulting in an excellent cosmetic outcome. This report describes step-by-step removal of a large lipoma located on the back, as well as a review of currently employed techniques for minimally invasive treatment of lipomas. © 2011 Wiley Periodicals, Inc.

  17. [Effect of protein-vitamin deficiency on the enzyme activity of lipolysis and the synthesis of cholesterol esters during hypokinesia].

    Science.gov (United States)

    Koshkenbaev, B Kh; Tazhibaev, Sh S; Maksimenko, V B; Sisemalieva, Zh S

    1985-01-01

    Balanced diet during 60-day hypokinesia leads to inhibition of lipoprotein lypase (LPLA) and liver triglyceride lypase (L-TGLA) activity of the rat blood serum. The level of very low density lipoproteins (VLDLP) grows, and suppression of lecithin-cholesteryl-acyltransferase (LCAT) activity is accompanied by reduction of the share of cholesterol derivatives with polyunsaturated fatty acids. Combined effects of protein-vitamin insufficiency and hypokinesia result in parversion of the lipolysis processes, that manifests in prevalence of L-TGLA over LPLA. The levels of VLDLP increase, and growth of LCAT activity is acompanied by the growth of cholesteryl linoleate share and level. Hypokinesia combined with the studied experimental diets was found to lead to increase of the free fatty acid level and to decrease of the blood serum levels of phospholipids and triglycerides.

  18. Lipolysis og different oils using crude enzyme isolate from the intestinal tract of rainbow trout, Oncorhynchus mykiss

    DEFF Research Database (Denmark)

    Göttsche, J.R.; Nielsen, Nina Skall; Nielsen, Henrik Hauch;

    2005-01-01

    lipase specificity of the enzyme isolate from rainbow trout tended to be 1,3-specific; however, activity against the sn -2 position also was shown. In vitro lipolysis of four different unlabeled oils was performed with the crude enzyme isolate. The oils were: structured lipid [SL; containing the medium......-chain FA (MCFA) 8:0 in the sn -1,3 positions and long-chain FA (LCFA) in the sn -2 position], DAGoil (mainly 1,3-DAG), fish oil (FO), and triolein (TO). MCFA were rapidly hydrolyzed from the SL oil. LCFA including n-3 PUFA were, however, preserved in the sn -2 position and therefore found in higher amounts...... that n-3 very long-chain PUFA from structured oils may be used betterby aquacultured fish than that from fish oils...

  19. Adipose Tissue Free Fatty Acid Storage In Vivo: Effects of Insulin Versus Niacin as a Control for Suppression of Lipolysis.

    Science.gov (United States)

    Ali, Asem H; Mundi, Manpreet; Koutsari, Christina; Bernlohr, David A; Jensen, Michael D

    2015-08-01

    Insulin stimulates the translocation fatty acid transport protein 1 (FATP1) to plasma membrane, and thus greater free fatty acid (FFA) uptake, in adipocyte cell models. Whether insulin stimulates greater FFA clearance into adipose tissue in vivo is unknown. We tested this hypothesis by comparing direct FFA storage in subcutaneous adipose tissue during insulin versus niacin-medicated suppression of lipolysis. We measured direct FFA storage in abdominal and femoral subcutaneous fat in 10 and 11 adults, respectively, during euglycemic hyperinsulinemia or after oral niacin to suppress FFA compared with 11 saline control experiments. Direct palmitate storage was assessed using a [U-(13)C]palmitate infusion to measure palmitate kinetics and an intravenous palmitate radiotracer bolus/timed biopsy. Plasma palmitate concentrations and flux were suppressed to 23 ± 3 and 26 ± 5 µmol ⋅ L(-1) (P = 0.91) and 44 ± 4 and 39 ± 5 µmol ⋅ min(-1) (P = 0.41) in the insulin and niacin groups, respectively, much less (P insulin, niacin, and saline groups, abdominal palmitate storage rates were 0.25 ± 0.05 vs. 0.25 ± 0.07 vs. 0.32 ± 0.05 µmol ⋅ kg adipose lipid(-1) ⋅ min(-1), respectively (P = NS), and femoral adipose storage rates were 0.19 ± 0.06 vs. 0.20 ± 0.05 vs. 0.31 ± 0.05 µmol ⋅ kg adipose lipid(-1) ⋅ min(-1), respectively (P = NS). In conclusion, insulin does not increase FFA storage in adipose tissue compared with niacin, which suppresses lipolysis via a different pathway. © 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.

  20. Differential phosphorylation of perilipin 1A at the initiation of lipolysis revealed by novel monoclonal antibodies and high content analysis.

    Science.gov (United States)

    McDonough, Patrick M; Maciejewski-Lenoir, Dominique; Hartig, Sean M; Hanna, Rita A; Whittaker, Ross; Heisel, Andrew; Nicoll, James B; Buehrer, Benjamin M; Christensen, Kurt; Mancini, Maureen G; Mancini, Michael A; Edwards, Dean P; Price, Jeffrey H

    2013-01-01

    Lipolysis in adipocytes is regulated by phosphorylation of lipid droplet-associated proteins, including perilipin 1A and hormone-sensitive lipase (HSL). Perilipin 1A is potentially phosphorylated by cAMP(adenosine 3',5'-cyclic monophosphate)-dependent protein kinase (PKA) on several sites, including conserved C-terminal residues, serine 497 (PKA-site 5) and serine 522 (PKA-site 6). To characterize perilipin 1A phosphorylation, novel monoclonal antibodies were developed, which selectively recognize perilipin 1A phosphorylation at PKA-site 5 and PKA-site 6. Utilizing these novel antibodies, as well as antibodies selectively recognizing HSL phosphorylation at serine 563 or serine 660, we used high content analysis to examine the phosphorylation of perilipin 1A and HSL in adipocytes exposed to lipolytic agents. We found that perilipin PKA-site 5 and HSL-serine 660 were phosphorylated to a similar extent in response to forskolin (FSK) and L-γ-melanocyte stimulating hormone (L-γ-MSH). In contrast, perilipin PKA-site 6 and HSL-serine 563 were phosphorylated more slowly and L-γ-MSH was a stronger agonist for these sites compared to FSK. When a panel of lipolytic agents was tested, including multiple concentrations of isoproterenol, FSK, and L-γ-MSH, the pattern of results was virtually identical for perilipin PKA-site 5 and HSL-serine 660, whereas a distinct pattern was observed for perilipin PKA-site 6 and HSL-serine 563. Notably, perilipin PKA-site 5 and HSL-serine 660 feature two arginine residues upstream from the phospho-acceptor site, which confers high affinity for PKA, whereas perilipin PKA-site 6 and HSL-serine 563 feature only a single arginine. Thus, we suggest perilipin 1A and HSL are differentially phosphorylated in a similar manner at the initiation of lipolysis and arginine residues near the target serines may influence this process.

  1. Morphometric analysis of high-intensity focused ultrasound-induced lipolysis on cadaveric abdominal and thigh skin.

    Science.gov (United States)

    Lee, Sugun; Kim, Hee-Jin; Park, Hyun Jun; Kim, Hyoung Moon; Lee, So Hyun; Cho, Sung Bin

    2017-07-01

    Non-focused ultrasound and high-intensity focused ultrasound (HIFU) devices induce lipolysis by generating acoustic cavitation and coagulation necrosis in targeted tissues. We aimed to investigate the morphometric characteristics of immediate tissue reactions induced by 2 MHz, 13-mm focused HIFU via two-dimensional ultrasound images and histologic evaluation of cadaveric skin from the abdomen and thigh. Acoustic fields of a 2 MHz, 38-mm HIFU transducer were characterized by reconstruction of the fields using acoustic intensity measurement. Additionally, abdominal and thigh tissues from a fresh cadaver were treated with a HIFU device for a single, two, and three pulses at the pulse energy of 130 J/cm(2) and a penetration depth of 13 mm. Acoustic intensity measurement revealed characteristic focal zones of significant thermal injury at the depth of 38 mm. In both the abdomen and thigh tissue, round to oval ablative thermal injury zones (TIZs) were visualized in subcutaneous fat layers upon treatment with a single pulse of HIFU treatment. Two to three HIFU pulses generated larger and more remarkable ablative zones throughout subcutaneous fat layers. Finally, experimental treatment in a tumescent infiltration-like setting induced larger HIFU-induced TIZs of an oval or columnar shape, compared to non-tumescent settings. Although neither acoustic intensity measurement nor cadaveric tissue exactly reflects in vivo HIFU-induced reactions in human tissue, we believe that our data will help guide further in vivo studies in investigating the therapeutic efficacy and safety of HIFU-induced lipolysis.

  2. Differential phosphorylation of perilipin 1A at the initiation of lipolysis revealed by novel monoclonal antibodies and high content analysis.

    Directory of Open Access Journals (Sweden)

    Patrick M McDonough

    Full Text Available Lipolysis in adipocytes is regulated by phosphorylation of lipid droplet-associated proteins, including perilipin 1A and hormone-sensitive lipase (HSL. Perilipin 1A is potentially phosphorylated by cAMP(adenosine 3',5'-cyclic monophosphate-dependent protein kinase (PKA on several sites, including conserved C-terminal residues, serine 497 (PKA-site 5 and serine 522 (PKA-site 6. To characterize perilipin 1A phosphorylation, novel monoclonal antibodies were developed, which selectively recognize perilipin 1A phosphorylation at PKA-site 5 and PKA-site 6. Utilizing these novel antibodies, as well as antibodies selectively recognizing HSL phosphorylation at serine 563 or serine 660, we used high content analysis to examine the phosphorylation of perilipin 1A and HSL in adipocytes exposed to lipolytic agents. We found that perilipin PKA-site 5 and HSL-serine 660 were phosphorylated to a similar extent in response to forskolin (FSK and L-γ-melanocyte stimulating hormone (L-γ-MSH. In contrast, perilipin PKA-site 6 and HSL-serine 563 were phosphorylated more slowly and L-γ-MSH was a stronger agonist for these sites compared to FSK. When a panel of lipolytic agents was tested, including multiple concentrations of isoproterenol, FSK, and L-γ-MSH, the pattern of results was virtually identical for perilipin PKA-site 5 and HSL-serine 660, whereas a distinct pattern was observed for perilipin PKA-site 6 and HSL-serine 563. Notably, perilipin PKA-site 5 and HSL-serine 660 feature two arginine residues upstream from the phospho-acceptor site, which confers high affinity for PKA, whereas perilipin PKA-site 6 and HSL-serine 563 feature only a single arginine. Thus, we suggest perilipin 1A and HSL are differentially phosphorylated in a similar manner at the initiation of lipolysis and arginine residues near the target serines may influence this process.

  3. Differential Phosphorylation of Perilipin 1A at the Initiation of Lipolysis Revealed by Novel Monoclonal Antibodies and High Content Analysis

    Science.gov (United States)

    McDonough, Patrick M.; Hanna, Rita A.; Whittaker, Ross; Heisel, Andrew; Nicoll, James B.; Buehrer, Benjamin M.; Christensen, Kurt; Mancini, Maureen G.; Mancini, Michael A.; Edwards, Dean P.; Price, Jeffrey H.

    2013-01-01

    Lipolysis in adipocytes is regulated by phosphorylation of lipid droplet-associated proteins, including perilipin 1A and hormone-sensitive lipase (HSL). Perilipin 1A is potentially phosphorylated by cAMP(adenosine 3′,5′-cyclic monophosphate)-dependent protein kinase (PKA) on several sites, including conserved C-terminal residues, serine 497 (PKA-site 5) and serine 522 (PKA-site 6). To characterize perilipin 1A phosphorylation, novel monoclonal antibodies were developed, which selectively recognize perilipin 1A phosphorylation at PKA-site 5 and PKA-site 6. Utilizing these novel antibodies, as well as antibodies selectively recognizing HSL phosphorylation at serine 563 or serine 660, we used high content analysis to examine the phosphorylation of perilipin 1A and HSL in adipocytes exposed to lipolytic agents. We found that perilipin PKA-site 5 and HSL-serine 660 were phosphorylated to a similar extent in response to forskolin (FSK) and L-γ-melanocyte stimulating hormone (L-γ-MSH). In contrast, perilipin PKA-site 6 and HSL-serine 563 were phosphorylated more slowly and L-γ-MSH was a stronger agonist for these sites compared to FSK. When a panel of lipolytic agents was tested, including multiple concentrations of isoproterenol, FSK, and L-γ-MSH, the pattern of results was virtually identical for perilipin PKA-site 5 and HSL-serine 660, whereas a distinct pattern was observed for perilipin PKA-site 6 and HSL-serine 563. Notably, perilipin PKA-site 5 and HSL-serine 660 feature two arginine residues upstream from the phospho-acceptor site, which confers high affinity for PKA, whereas perilipin PKA-site 6 and HSL-serine 563 feature only a single arginine. Thus, we suggest perilipin 1A and HSL are differentially phosphorylated in a similar manner at the initiation of lipolysis and arginine residues near the target serines may influence this process. PMID:23405163

  4. Adipose tissue loss in adjuvant arthritis is associated with a decrease in lipogenesis, but not with an increase in lipolysis.

    Science.gov (United States)

    Martín, A I; Castillero, E; Granado, M; López-Menduiña, M; Villanúa, M A; López-Calderón, A

    2008-04-01

    Adjuvant-induced arthritis is a model of rheumatoid arthritis that induces cachexia. In other cachectic situations, there is an increase in lipolysis resulting in a loss of adipose tissue mass. The aim of this work was to analyse the effect of chronic arthritis, induced by adjuvant injection, on white adipose tissue (WAT). For this purpose, rats were killed 10 days after adjuvant injection, when the first external symptoms appeared, on days 15 and 22 when the external signs of the illness reach their severest level. As arthritis decreases food intake, a pair-fed group was also included. Serum concentrations of insulin, leptin, adiponectin, glycerol and nitrites, as well as gene expression of leptin, adiponectin, hormone-sensitive lipase (HSL), fatty acid synthase (FAS), tumour necrosis factor alpha and zinc-alpha(2)-glycoprotein (ZAG) were determined. Arthritis decreased food intake between days 5 and 16, but not during the last 5 days of the experiment. There was a marked decrease in relative adipose tissue weight and in serum leptin and adiponectin as well as in their gene expression in WAT in arthritic rats. Arthritis decreased the gene expression of FAS in the WAT. However, none of these effects was found in pair-fed rats. Arthritis did not increase lipolysis, since arthritic rats have lower serum concentrations of glycerol, HSL mRNA in WAT, as well as liver ZAG mRNA than the pair-fed or control rats. These data suggest that in chronic arthritis the decrease in white adipose mass is secondary to a reduced adipose lipogenesis, and this effect is not mainly due to the decrease in food intake.

  5. Fish oil -- how does it reduce plasma triglycerides?

    Science.gov (United States)

    Shearer, Gregory C; Savinova, Olga V; Harris, William S

    2012-05-01

    Long chain omega-3 fatty acids (FAs) are effective for reducing plasma triglyceride (TG) levels. At the pharmaceutical dose, 3.4g/day, they reduce plasma TG by about 25-50% after one month of treatment, resulting primarily from the decline in hepatic very low density lipoprotein (VLDL-TG) production, and secondarily from the increase in VLDL clearance. Numerous mechanisms have been shown to contribute to the TG overproduction, but a key component is an increase in the availability of FAs in the liver. The liver derives FAs from three sources: diet (delivered via chylomicron remnants), de novo lipogenesis, and circulating non-esterified FAs (NEFAs). Of these, NEFAs contribute the largest fraction to VLDL-TG production in both normotriglyceridemic subjects and hypertriglyceridemic, insulin resistant patients. Thus reducing NEFA delivery to the liver would be a likely locus of action for fish oils (FO). The key regulator of plasma NEFA is intracellular adipocyte lipolysis via hormone sensitive lipase (HSL), which increases as insulin sensitivity worsens. FO counteracts intracellular lipolysis in adipocytes by suppressing adipose tissue inflammation. In addition, FO increases extracellular lipolysis by lipoprotein lipase (LpL) in adipose, heart and skeletal muscle and enhances hepatic and skeletal muscle β-oxidation which contributes to reduced FA delivery to the liver. FO could activate transcription factors which control metabolic pathways in a tissue specific manner regulating nutrient traffic and reducing plasma TG. This article is part of a Special Issue entitled Triglyceride Metabolism and Disease.

  6. Development of a high-throughput in vitro intestinal lipolysis model for rapid screening of lipid-based drug delivery systems

    DEFF Research Database (Denmark)

    Mosgaard, Mette D; Sassene, Philip; Mu, Huiling

    2015-01-01

    PURPOSE: To develop a high-throughput in vitro intestinal lipolysis (HTP) model, without any means of pH-stat-titration, to enable a fast evaluation of lipid-based drug delivery systems (LbDDS). MATERIAL AND METHOD: The HTP model was compared to the traditionally used dynamic in vitro lipolysis...... (DIVL) model with regard to the extent of lipid digestion and drug distribution of two poorly soluble model drugs (cinnarizine and danazol), during digestion of three LbDDS (LbDDS I-III). RESULT: The HTP model was able to maintain pH around 6.5 during digestion, without the addition of Na......OH to neutralize the free fatty acids (FFAs), due to an increased buffer capacity. Cinnarizine was primarily located in the aqueous phase during digestion of all three LbDDS and did not differ significantly between the two models. The distribution of danazol varied from formulation to formulation...

  7. Original Research: Hydroxytyrosol, an ingredient of olive oil, reduces triglyceride accumulation and promotes lipolysis in human primary visceral adipocytes during differentiation.

    Science.gov (United States)

    Stefanon, Bruno; Colitti, Monica

    2016-10-01

    Hydroxytyrosol has various pharmacological properties, including anti-oxidative stress and anti-inflammatory activities, preventing hyperglycemia, insulin resistance, and the metabolic syndrome. The present study is focused on the anti-adipogenic and lipolytic activity of hydroxytyrosol on primary human visceral adipocytes. Pre-adipocytes were analyzed after 10 (P10) and 20 (P20) days of treatment during differentiation and after 7 (A7) days of treatment when they reached mature shape. The treatment with hydroxytyrosol extract significantly (P lipolysis in P20 cells in comparison to control cells and A7 mature adipocytes. Hydroxytyrosol-treated P20 cells significantly (P lipolysis and apoptotic activity in primary human visceral pre-adipocytes during differentiation and does not affect already mature adipocytes. © 2016 by the Society for Experimental Biology and Medicine.

  8. Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women

    DEFF Research Database (Denmark)

    Koppo, Katrien; Siklová-Vitková, Michaela; Klimcáková, Eva

    2012-01-01

    at baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during...... the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM......, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α(2)-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned...

  9. Catecholamine and insulin control of lipolysis in subcutaneous adipose tissue during long-term diet-induced weight loss in obese women.

    Science.gov (United States)

    Koppo, Katrien; Siklová-Vitková, Michaela; Klimcáková, Eva; Polák, Jan; Marques, Marie A; Berlan, Michel; Van de Voorde, Johan; Bulow, Jens; Langin, Dominique; de Glisezinski, Isabelle; Stich, Vladimir

    2012-01-15

    The aim of this study was to investigate the evolution of the adrenergic and insulin-mediated regulation of lipolysis during different phases of a 6-mo dietary intervention. Eight obese women underwent a 6-mo dietary intervention consisting of a 1-mo very low-calorie diet (VLCD) followed by a 2-mo low-calorie diet (LCD) and 3-mo weight maintenance (WM) diet. At each phase of the dietary intervention, microdialysis of subcutaneous adipose tissue (SCAT) was performed at rest and during a 3-h hyperinsulinemic euglycemic clamp. Responses of dialysate glycerol concentration (DGC) were determined at baseline and during local perfusions with adrenaline or adrenaline and phentolamine before and during the last 30 min of the clamp. Dietary intervention induced a body weight reduction and an improved insulin sensitivity. DGC progressively decreased during the clamp, and this decrease was similar during the different phases of the diet. The adrenaline-induced increase in DGC was higher at VLCD and LCD compared with baseline condition and returned to prediet levels at WM. In the probe with adrenaline and phentolamine, the increase in DGC was higher than that in the adrenaline probe at baseline and WM, but it was not different at VLCD and LCD. The results suggest that the responsiveness of SCAT to adrenaline-stimulated lipolysis increases during the calorie-restricted phases due to a reduction of the α(2)-adrenoceptor-mediated antilipolytic action of adrenaline. At WM, adrenaline-stimulated lipolysis returned to the prediet levels. Furthermore, no direct relationship between insulin sensitivity and the diet-induced changes in the regulation of lipolysis was found.

  10. Neuropeptide Y and peptide YY inhibit lipolysis in human and dog fat cells through a pertussis toxin-sensitive G protein.

    OpenAIRE

    Valet, P; Berlan, M.; BEAUVILLE, M.; Crampes, F.; Montastruc, J L; Lafontan, M.

    1990-01-01

    Neuropeptide Y (NPY) and peptide YY (PYY) are regulatory peptides that have considerable sequence homology with pancreatic polypeptide. Because (a) NPY has been shown to be colocalized with noradrenaline in peripheral as well as central catecholaminergic neurons, and (b) alpha 2-adrenergic receptors of adipocytes play a major role in the regulation of lipolysis, we investigated the effect of NPY and PYY on isolated fat cells. In human fat cells NPY and PYY promoted a dose-dependent inhibition...