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Sample records for adipose triglyceride lipase

  1. Efficient Phagocytosis Requires Triacylglycerol Hydrolysis by Adipose Triglyceride Lipase*

    Chandak, Prakash G.; Radović, Branislav; Aflaki, Elma; Kolb, Dagmar; Buchebner, Marlene; Fröhlich, Eleonore; Magnes, Christoph; Sinner, Frank; Haemmerle, Guenter; Zechner, Rudolf; Tabas, Ira; Levak-Frank, Sanja; Kratky, Dagmar

    2010-01-01

    Macrophage phagocytosis is an essential biological process in host defense and requires large amounts of energy. To date, glucose is believed to represent the prime substrate for ATP production in macrophages. To investigate the relative contribution of free fatty acids (FFAs) in this process, we determined the phagocytosis rates in normal mouse macrophages and macrophages of adipose triglyceride lipase (ATGL)-deficient mice. ATGL was shown to be the rate-limiting enzyme for the hydrolysis of...

  2. Adipose Triglyceride Lipase (ATGL) and Hormone-Sensitive Lipase (HSL) Deficiencies Affect Expression of Lipolytic Activities in Mouse Adipose Tissues*

    Morak, Maria; Schmidinger, Hannes; Riesenhuber, Gernot; Rechberger, Gerald N.; Kollroser, Manfred; Haemmerle, Guenter; Zechner, Rudolf; Kronenberg, Florian; Hermetter, Albin

    2012-01-01

    Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are key enzymes involved in intracellular degradation of triacylglycerols. It was the aim of this study to elucidate how the deficiency in one of these proteins affects the residual lipolytic proteome in adipose tissue. For this purpose, we compared the lipase patters of brown and white adipose tissue from ATGL (−/−) and HSL (−/−) mice using differential activity-based gel electrophoresis. This method is based on activity-r...

  3. Efficient phagocytosis requires triacylglycerol hydrolysis by adipose triglyceride lipase.

    Chandak, Prakash G; Radovic, Branislav; Aflaki, Elma; Kolb, Dagmar; Buchebner, Marlene; Fröhlich, Eleonore; Magnes, Christoph; Sinner, Frank; Haemmerle, Guenter; Zechner, Rudolf; Tabas, Ira; Levak-Frank, Sanja; Kratky, Dagmar

    2010-06-25

    Macrophage phagocytosis is an essential biological process in host defense and requires large amounts of energy. To date, glucose is believed to represent the prime substrate for ATP production in macrophages. To investigate the relative contribution of free fatty acids (FFAs) in this process, we determined the phagocytosis rates in normal mouse macrophages and macrophages of adipose triglyceride lipase (ATGL)-deficient mice. ATGL was shown to be the rate-limiting enzyme for the hydrolysis of lipid droplet-associated triacylglycerol (TG) in many tissues. Here, we demonstrate that Atgl(-/-) macrophages fail to efficiently hydrolyze cellular TG stores leading to decreased cellular FFA concentrations and concomitant accumulation of lipid droplets, even in the absence of exogenous lipid loading. The reduced availability of FFAs results in decreased cellular ATP concentrations and impaired phagocytosis suggesting that fatty acids must first go through a cycle of esterification and re-hydrolysis before they are available as energy substrate. Exogenously added glucose cannot fully compensate for the phagocytotic defect in Atgl(-/-) macrophages. Hence, phagocytosis was also decreased in vivo when Atgl(-/-) mice were challenged with bacterial particles. These findings imply that phagocytosis in macrophages depends on the availability of FFAs and that ATGL is required for their hydrolytic release from cellular TG stores. This novel mechanism links ATGL-mediated lipolysis to macrophage function in host defense and opens the way to explore possible roles of ATGL in immune response, inflammation, and atherosclerosis. PMID:20424161

  4. Contribution of Adipose Triglyceride Lipase and Hormone-sensitive Lipase to Lipolysis in hMADS Adipocytes*

    Bezaire, Véronic; Mairal, Aline; Ribet, Carole; Lefort, Corinne; Girousse, Amandine; Jocken, Johan; Laurencikiene, Jurga; Anesia, Rodica; Rodriguez, Anne-Marie; Ryden, Mikael; Stenson, Britta M.; Dani, Christian; Ailhaud, Gérard; Arner, Peter; Langin, Dominique

    2009-01-01

    Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS ...

  5. ADIPOSE TRIGLYCERIDE LIPASE REGULATES BASAL LIPOLYSIS AND LIPID DROPLET SIZE IN ADIPOCYTES

    Miyoshi, Hideaki; Perfield, James W.; Obin, Martin S.; Greenberg, Andrew S.

    2008-01-01

    In adipocytes, lipid droplet (LD) size reflects a balance of triglyceride synthesis (lipogenesis) and hydrolysis (lipolysis). Perilipin A (Peri A), is the most abundant phosphoprotein on the surface of adipocyte LDs and has a crucial role in lipid storage and lipolysis. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) are the major rate-determining enzymes for lipolysis in adipocytes. Each of these proteins (Peri A, ATGL and HSL) have been demonstrated to regulate lipid s...

  6. Absence of adipose triglyceride lipase protects from hepatic endoplasmic reticulum stress in mice

    Fuchs, Claudia D.; Claudel, Thierry; Kumari, Pooja; Haemmerle, Guenter; Pollheimer, Marion J.; Stojakovic, Tatjana; Scharnagl, Hubert; Halilbasic, Emina; Gumhold, Judith; Silbert, Dagmar; Koefeler, Harald; Trauner, Michael

    2012-01-01

    Nonalcoholic fatty liver disease (NAFLD) is characterized by triglyceride (TG) accumulation and endoplasmic reticulum (ER) stress. Because fatty acids (FAs) may trigger ER stress, we hypothesized that the absence of adipose triglyceride lipase (ATGL/PNPLA2)-the main enzyme for intracellular lipolysis, releasing FAs, and closest homolog to adiponutrin (PNPLA3) recently implicated in the pathogenesis of NAFLD-protects against hepatic ER stress. Wild-type (WT) and ATGL knockout (KO) mice were ch...

  7. Adipose triglyceride lipase in human skeletal muscle is upregulated by exercise training

    Alsted, Thomas J; Schweiger, Martina; Nybo, Lars;

    2009-01-01

    ) is not changed. Recently, adipose triglyceride lipase (ATGL) was identified as a TG-specific lipase in various rodent tissues. To investigate whether human skeletal muscle ATGL protein is regulated by endurance exercise training, 10 healthy young men completed 8 wk of supervised endurance exercise...... training. Western blotting analysis on lysates of skeletal muscle biopsy samples revealed that exercise training induced a twofold increase in skeletal muscle ATGL protein content. In contrast to ATGL, expression of comparative gene identification 58 (CGI-58), the activating protein of ATGL, and HSL......Mobilization of fatty acids from stored triacylglycerol (TG) in adipose tissue and skeletal muscle [intramyocellular triacylglycerol (IMTG)] requires activity of lipases. Although exercise training increases the lipolytic capacity of skeletal muscle, the expression of hormone-sensitive lipase (HSL...

  8. Adipose triglyceride lipase deletion from adipocytes, but not skeletal myocytes, impairs acute exercise performance in mice

    Dubé, John J.; Sitnick, Mitch T.; Schoiswohl, Gabriele; Wills, Rachel C.; Basantani, Mahesh K.; Cai, Lingzhi; Pulinilkunnil, Thomas; Kershaw, Erin E.

    2015-01-01

    Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triacylglycerol hydrolysis in virtually all cells, including adipocytes and skeletal myocytes, and hence, plays a critical role in mobilizing fatty acids. Global ATGL deficiency promotes skeletal myopathy and exercise intolerance in mice and humans, and yet the tissue-specific contributions to these phenotypes remain unknown. The goal of this study was to determine the relative contribution of ATGL-mediated triacylglycer...

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

    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)physiologi...

  10. Adipose Triglyceride Lipase Deficiency Causes Tissue-specific Changes in Insulin Signaling*

    Kienesberger, Petra C.; Lee, Daeho; Pulinilkunnil, Thomas; Brenner, Daniel S.; Cai, Lingzhi; Magnes, Christoph; Koefeler, Harald C.; Streith, Ingo E.; Rechberger, Gerald N.; Haemmerle, Guenter; Flier, Jeffrey S.; Zechner, Rudolf; Kim, Young-Bum; Kershaw, Erin E.

    2009-01-01

    Triacylglycerol accumulation in insulin target tissues is associated with insulin resistance. Paradoxically, mice with global targeted deletion of adipose triglyceride lipase (ATGL), the rate-limiting enzyme in triacylglycerol hydrolysis, display improved glucose tolerance and insulin sensitivity despite triacylglycerol accumulation in multiple tissues. To determine the molecular mechanisms for this phenotype, ATGL-deficient (ATGL−/−) and wild-type mice were injected with saline or insulin (1...

  11. Contribution of adipose triglyceride lipase and hormone-sensitive lipase to lipolysis in hMADS adipocytes.

    Bezaire, Véronic; Mairal, Aline; Ribet, Carole; Lefort, Corinne; Girousse, Amandine; Jocken, Johan; Laurencikiene, Jurga; Anesia, Rodica; Rodriguez, Anne-Marie; Ryden, Mikael; Stenson, Britta M; Dani, Christian; Ailhaud, Gérard; Arner, Peter; Langin, Dominique

    2009-07-01

    Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS cells. The hMADS adipocytes express the various components of fatty acid metabolism and show lipolytic capacity similar to primary cultured adipocytes. We show that lipolysis and fatty acid esterification are tightly coupled except in conditions of stimulated lipolysis. Immunocytochemistry experiments revealed that acute forskolin treatment promotes HSL translocation from the cytosol to small lipid droplets and redistribution of ATGL from the cytosol and large lipid droplets to small lipid droplets, resulting in enriched colocalization of the two lipases. HSL or ATGL overexpression resulted in increased triglyceride-specific hydrolase capacity, but only ATGL overexpression increased whole cell lipolysis. HSL silencing had no effect on basal lipolysis and only partially reduced forskolin-stimulated lipolysis. Conversely, silencing of ATGL or CGI-58 significantly reduced basal lipolysis and essentially abolished forskolin-stimulated lipolysis. Altogether, these results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes. PMID:19433586

  12. Contribution of Adipose Triglyceride Lipase and Hormone-sensitive Lipase to Lipolysis in hMADS Adipocytes*

    Bezaire, Véronic; Mairal, Aline; Ribet, Carole; Lefort, Corinne; Girousse, Amandine; Jocken, Johan; Laurencikiene, Jurga; Anesia, Rodica; Rodriguez, Anne-Marie; Ryden, Mikael; Stenson, Britta M.; Dani, Christian; Ailhaud, Gérard; Arner, Peter; Langin, Dominique

    2009-01-01

    Lipolysis is the catabolic pathway by which triglycerides are hydrolyzed into fatty acids. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) have the capacity to hydrolyze in vitro the first ester bond of triglycerides, but their respective contributions to whole cell lipolysis in human adipocytes is unclear. Here, we have investigated the roles of HSL, ATGL, and its coactivator CGI-58 in basal and forskolin-stimulated lipolysis in a human white adipocyte model, the hMADS cells. The hMADS adipocytes express the various components of fatty acid metabolism and show lipolytic capacity similar to primary cultured adipocytes. We show that lipolysis and fatty acid esterification are tightly coupled except in conditions of stimulated lipolysis. Immunocytochemistry experiments revealed that acute forskolin treatment promotes HSL translocation from the cytosol to small lipid droplets and redistribution of ATGL from the cytosol and large lipid droplets to small lipid droplets, resulting in enriched colocalization of the two lipases. HSL or ATGL overexpression resulted in increased triglyceride-specific hydrolase capacity, but only ATGL overexpression increased whole cell lipolysis. HSL silencing had no effect on basal lipolysis and only partially reduced forskolin-stimulated lipolysis. Conversely, silencing of ATGL or CGI-58 significantly reduced basal lipolysis and essentially abolished forskolin-stimulated lipolysis. Altogether, these results suggest that ATGL/CGI-58 acts independently of HSL and precedes its action in the sequential hydrolysis of triglycerides in human hMADS adipocytes. PMID:19433586

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

    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. Adipose triglyceride lipase regulates lipid metabolism in dairy goat mammary epithelial cells.

    Li, Jun; Luo, Jun; Wang, Hui; Shi, Hengbo; Zhu, Jiangjiang; Sun, Yuting; Yu, Kang; Yao, Dawei

    2015-01-01

    Adipose triglyceride lipase (ATGL) catalyzes the initial step in the lipid lipolysis process, hydrolyzing triglyceride (TG) to produce diacylglycerol (DG) and free fatty acids (FFA). In addition, ATGL regulates lipid storage and release in adipocyte cells. However, its role in mammary gland tissue remains unclear. To assess the role of the ATGL gene in the goat mammary gland, this study analyzed the tissue distribution and expression of key genes together with lipid accumulation after knockdown of the ATGL gene. The mRNA of ATGL was highly expressed in subcutaneous adipose tissue, the lung and the mammary gland with a significant increase in expression during the lactation period compared with the dry period of the mammary gland. Knockdown of the ATGL gene in goat mammary epithelial cells (GMECs) using siRNA resulted in a significant decrease in both ATGL mRNA and protein levels. Silencing of the ATGL gene markedly increased lipid droplet accumulation and intracellular TG concentration (Pfat formation and secretion was down-regulated (PCD36 for fatty acid uptake (P<0.05). In conclusion, these data suggest that the ATGL gene plays an important role in triglyceride lipolysis in GMECs and provides the first experimental evidence that ATGL may be involved in lipid metabolism during lactation. PMID:25307872

  15. Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis.

    Rydén, Mikael; Jocken, Johan; van Harmelen, Vanessa; Dicker, Andrea; Hoffstedt, Johan; Wirén, Mikael; Blomqvist, Lennart; Mairal, Aline; Langin, Dominique; Blaak, Ellen; Arner, Peter

    2007-06-01

    Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) regulate adipocyte lipolysis in rodents. The purpose of this study was to compare the roles of these lipases for lipolysis in human adipocytes. Subcutaneous adipose tissue was investigated. HSL and ATGL protein expression were related to lipolysis in isolated mature fat cells. ATGL or HSL were knocked down by RNA interference (RNAi) or selectively inhibited, and effects on lipolysis were studied in differentiated preadipocytes or adipocytes derived from human mesenchymal stem cells (hMSC). Subjects were all women. There were 12 lean controls, 8 lean with polycystic ovary syndrome (PCOS), and 27 otherwise healthy obese subjects. We found that norepinephrine-induced lipolysis was positively correlated with HSL protein levels (P < 0.0001) but not with ATGL protein. Women with PCOS or obesity had significantly decreased norepinephrine-induced lipolysis and HSL protein expression but no change in ATGL protein expression. HSL knock down by RNAi reduced basal and catecholamine-induced lipolysis. Knock down of ATGL decreased basal lipolysis but did not change catecholamine-stimulated lipolysis. Treatment of hMSC with a selective HSL inhibitor during and/or after differentiation in adipocytes reduced basal lipolysis by 50%, but stimulated lipolysis was inhibited completely. In contrast to findings in rodents, ATGL is of less importance than HSL in regulating catecholamine-induced lipolysis and cannot replace HSL when this enzyme is continuously inhibited. However, both lipases regulate basal lipolysis in human adipocytes. ATGL expression, unlike HSL, is not influenced by obesity or PCOS. PMID:17327373

  16. New Atglistatin closely related analogues: Synthesis and structure-activity relationship towards adipose triglyceride lipase inhibition.

    Roy, Pierre-Philippe; D'Souza, Kenneth; Cuperlovic-Culf, Miroslava; Kienesberger, Petra C; Touaibia, Mohamed

    2016-08-01

    Adipose Triglyceride Lipase (ATGL) performs the first and rate-limiting step in lipolysis by hydrolyzing triacylglycerols stored in lipid droplets to diacylglycerols. By mediating lipolysis in adipose and non-adipose tissues, ATGL is a major regulator of overall energy metabolism and plasma lipid levels. Since chronically high levels of plasma lipids are linked to metabolic disorders including insulin resistance and type 2 diabetes, ATGL is an interesting therapeutic target. In the present study, fourteen closely related analogues of Atglistatin (1), a newly discovered ATGL inhibitor, were synthesized, and their ATGL inhibitory activity was evaluated. The effect of these analogues on lipolysis in 3T3-L1 adipocytes clearly shows that inhibition of the enzyme by Atglistatin (1) is due to the presence of the carbamate and N,N-dimethyl moieties on the biaryl central core at meta and para position, respectively. Mono carbamate-substituted analogue C2, in which the carbamate group was in the meta position as in Atglistatin (1), showed slight inhibition. Low dipole moment of Atglistatin (1) compared to the synthesized analogues possibly explains the lower inhibitory activities. PMID:27155760

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

    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

    2012-01-01

    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), 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 overexp...

  18. Adipose triglyceride lipase plays a key role in the supply of the working muscle with fatty acids

    Schoiswohl, Gabriele; Schweiger, Martina; Schreiber, Renate; Gorkiewicz, Gregor; Preiss-Landl, Karina; Taschler, Ulrike; Zierler, Kathrin A.; Radner, Franz P. W.; Eichmann, Thomas O.; Kienesberger, Petra C; Eder, Sandra; Lass, Achim; Haemmerle, Guenter; Alsted, Thomas Junker; Kiens, Bente; Hoefler, Gerald; Zechner, Rudolf; Zimmermann, Robert

    2010-01-01

    during exercise. The reduced availability of FA for energy conversion led to rapid depletion of liver glycogen stores and hypoglycemia. Together, our studies suggest that ATGL-ko mice cannot adjust circulating FA levels to the increased energy requirements of the working muscle resulting in an increased......Fatty acids (FA) are mobilized from triglyceride (TG) stores during exercise to supply the working muscle with energy. Mice deficient for adipose triglyceride lipase (ATGLko)exhibit defective lipolysis and accumulate TG in adipose tissue and muscle suggesting that ATGL deficiency affects energy...... availability and substrate utilization in working muscle. In this study, we investigated the effect of moderate treadmill exercise on blood energy metabolites and liver glycogen stores in mice lacking ATGL. Since ATGL-ko mice exhibit massive accumulation of TG in the heart and cardiomyopathy, we also...

  19. Data on hepatic lipolysis, adipose triglyceride lipase, and hormone-sensitive lipase in fasted and non-fasted C57BL/6J female mice.

    Marvyn, Phillip M; Mardian, Emily B; Bradley, Ryan M; A Marks, Kristin; Duncan, Robin E

    2016-06-01

    Liver homogenates produced from fasted and non-fasted C57BL/6J female mice were assayed for total lipolytic activity measured as hydrolysis of [9,10-(3)H(N)]-triolein into [(3)H] free fatty acids (FFA). Liver homogenates were also used for immunoblotting to determine levels of the lipolytic enzymes adipose-triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), as well as site specific phosphorylation at the 14-3-3 binding site of ATGL and the serine 565 and serine 660 sites of HSL. Significantly higher triolein hydrolysis activity was observed in fasted liver samples, as well as a significant increase in total ATGL and a significant decrease in HSL phosphorylation at the S565 site. PMID:27054184

  20. Application of a sensitive collection heuristic for very large protein families: Evolutionary relationship between adipose triglyceride lipase (ATGL and classic mammalian lipases

    Berezovsky Igor

    2006-03-01

    Full Text Available Abstract Background Manually finding subtle yet statistically significant links to distantly related homologues becomes practically impossible for very populated protein families due to the sheer number of similarity searches to be invoked and analyzed. The unclear evolutionary relationship between classical mammalian lipases and the recently discovered human adipose triglyceride lipase (ATGL; a patatin family member is an exemplary case for such a problem. Results We describe an unsupervised, sensitive sequence segment collection heuristic suitable for assembling very large protein families. It is based on fan-like expanding, iterative database searches. To prevent inclusion of unrelated hits, additional criteria are introduced: minimal alignment length and overlap with starting sequence segments, finding starting sequences in reciprocal searches, automated filtering for compositional bias and repetitive patterns. This heuristic was implemented as FAMILYSEARCHER in the ANNIE sequence analysis environment and applied to search for protein links between the classical lipase family and the patatin-like group. Conclusion The FAMILYSEARCHER is an efficient tool for tracing distant evolutionary relationships involving large protein families. Although classical lipases and ATGL have no obvious sequence similarity and differ with regard to fold and catalytic mechanism, homology links detected with FAMILYSEARCHER show that they are evolutionarily related. The conserved sequence parts can be narrowed down to an ancestral core module consisting of three β-strands, one α-helix and a turn containing the typical nucleophilic serine. Moreover, this ancestral module also appears in numerous enzymes with various substrate specificities, but that critically rely on nucleophilic attack mechanisms.

  1. Identification of a novel phosphorylation site in adipose triglyceride lipase as a regulator of lipid droplet localization.

    Xie, Xitao; Langlais, Paul; Zhang, Xiaodong; Heckmann, Bradlee L; Saarinen, Alicia M; Mandarino, Lawrence J; Liu, Jun

    2014-06-15

    Adipose triglyceride lipase (ATGL), the rate-limiting enzyme for triacylglycerol (TG) hydrolysis, has long been known to be a phosphoprotein. However, the potential phosphorylation events that are involved in the regulation of ATGL function remain incompletely defined. Here, using a combinatorial proteomics approach, we obtained evidence that at least eight different sites of ATGL can be phosphorylated in adipocytes. Among them, Thr³⁷² resides within the hydrophobic region known to mediate lipid droplet (LD) targeting. Although it had no impact on the TG hydrolase activity, substitution of phosphorylation-mimic Asp for Thr³⁷² eliminated LD localization and LD-degrading capacity of ATGL expressed in HeLa cells. In contrast, mutation of Thr³⁷² to Ala gave a protein that bound LDs and functioned the same as the wild-type protein. In nonstimulated adipocytes, the Asp mutation led to decreased LD association and basal lipolytic activity of ATGL, whereas the Ala mutation produced opposite effects. Moreover, the LD translocation of ATGL upon β-adrenergic stimulation was also compromised by the Asp mutation. In accord with these findings, the Ala mutation promoted and the Asp mutation attenuated the capacity of ATGL to mediate lipolysis in adipocytes under both basal and stimulated conditions. Collectively, these studies identified Thr³⁷² as a novel phosphorylation site that may play a critical role in determining subcellular distribution as well as lipolytic action of ATGL. PMID:24801391

  2. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy

    Hirano, Ken-ichi, E-mail: khirano@cnt-osaka.com [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Tanaka, Tatsuya [Center for Medical Research and Education, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Ikeda, Yoshihiko [Department of Pathology, National Cerebral and Cardiovascular Center, 5-7-1 Fujishirodai, Suita 565-8565 (Japan); Yamaguchi, Satoshi [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Zaima, Nobuhiro [Department of Applied Biochemistry, Kinki University, 3327-204, Nakamachi, Nara 631-8505 (Japan); Kobayashi, Kazuhiro [Division of Neurology/Molecular Brain Science, Kobe University Graduate School of Medicine, 7-5-1, Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017 (Japan); Suzuki, Akira [Laboratory of Cardiovascular Disease, Novel, Non-Invasive, and Nutritional Therapeutics (CNT), Graduate School of Medicine, Osaka University, 6-2-3, Furuedai, Suita, Osaka 565-0874 (Japan); Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Sakata, Yasuhiko [Department of Cardiovascular Medicine, Graduate School of Medicine, Osaka University, 2-2, Yamadaoka, Suita, Osaka 565-0871 (Japan); Department of Cardiovascular Medicine, Tohoku University Graduate School of Medicine, 1-1, Seiryo-cho, Aoba-ku, Sendai 980-8574 (Japan); and others

    2014-01-10

    Highlights: •Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare severe heart disease. •PPARγ is up-regulated in myocardium in patients with TGCV. •Possible vicious cycle for fatty acid may be involved in pathophysiology of TGCV. -- Abstract: Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, “Triglyceride deposit cardiomyovasculopathy (TGCV)”. Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5′ splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules’ lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients’ passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG

  3. Genetic mutations in adipose triglyceride lipase and myocardial up-regulation of peroxisome proliferated activated receptor-γ in patients with triglyceride deposit cardiomyovasculopathy

    Highlights: •Triglyceride deposit cardiomyovasculopathy (TGCV) is a rare severe heart disease. •PPARγ is up-regulated in myocardium in patients with TGCV. •Possible vicious cycle for fatty acid may be involved in pathophysiology of TGCV. -- Abstract: Adipose triglyceride lipase (ATGL, also known as PNPLA2) is an essential molecule for hydrolysis of intracellular triglyceride (TG). Genetic ATGL deficiency is a rare multi-systemic neutral lipid storage disease. Information regarding its clinical profile and pathophysiology, particularly for cardiac involvement, is still very limited. A previous middle-aged ATGL-deficient patient in our institute (Case 1) with severe heart failure required cardiac transplantation (CTx) and exhibited a novel phenotype, “Triglyceride deposit cardiomyovasculopathy (TGCV)”. Here, we tried to elucidate molecular mechanism underlying TGCV. The subjects were two cases with TGCV, including our second case who was a 33-year-old male patient (Case 2) with congestive heart failure requiring CTx. Case 2 was homozygous for a point mutation in the 5′ splice donor site of intron 5 in the ATGL, which results in at least two types of mRNAs due to splicing defects. The myocardium of both patients (Cases 1 and 2) showed up-regulation of peroxisome proliferated activated receptors (PPARs), key transcription factors for metabolism of long chain fatty acids (LCFAs), which was in contrast to these molecules’ lower expression in ATGL-targeted mice. We investigated the intracellular metabolism of LCFAs under human ATGL-deficient conditions using patients’ passaged skin fibroblasts as a model. ATGL-deficient cells showed higher uptake and abnormal intracellular transport of LCFA, resulting in massive TG accumulation. We used these findings from cardiac specimens and cell-biological experiments to construct a hypothetical model to clarify the pathophysiology of the human disorder. In patients with TGCV, even when hydrolysis of intracellular TG

  4. Lipase Based Biosensors for Triglyceride Determination

    Rosli Nurul Huwaida; Mohd Zain Zainiharyati; Ahmad Nor Monica

    2016-01-01

    A review of methods development in lipase based biosensor for triglyceride determination was briefly discussed. This review focuses on the basic principle of triglyceride biosensor that includes performances of triglyceride biosensor such as limit of detection, response time, and optimization.

  5. Adipose triglyceride lipase (Atgl) mediates the antibiotic jinggangmycin-stimulated reproduction in the brown planthopper, Nilaparvata lugens Stål.

    Jiang, Yi-Ping; Li, Lei; Liu, Zong-Yu; You, Lin-Lin; Wu, You; Xu, Bing; Ge, Lin-Quan; Song, Qi-Sheng; Wu, Jin-Cai

    2016-01-01

    The antibiotic jinggangmycin (JGM) is an agrochemical product widely used in China for controlling rice sheath blight, Rhizoctonia solani. Unexpectedly, it stimulates reproduction in the brown planthopper (BPH), Nilaparvata lugens (Stål). However, the underlying molecular mechanisms of the stimulation are unclear. The present investigation demonstrates that adipose triglyceride lipase (Atgl) is one of the enzymes involved in the JGM-stimulated reproduction in BPH. Silence of Atgl in JGM-treated (JGM + dsAtgl) females eliminated JGM-stimulated fecundity of BPH females. In addition, Atgl knockdown significantly reduced the protein and glycerin contents in the ovaries and fat bodies of JGM + dsAtgl females required for reproduction. We conclude that Atgl is one of the key enzymes responsible for JGM-stimulated reproduction in BPH. PMID:26739506

  6. The minimal domain of adipose triglyceride lipase (ATGL ranges until leucine 254 and can be activated and inhibited by CGI-58 and G0S2, respectively.

    Irina Cornaciu

    Full Text Available Adipose triglyceride lipase (ATGL is the rate-limiting enzyme of lipolysis. ATGL specifically hydrolyzes triacylglycerols (TGs, thereby generating diacylglycerols and free fatty acids. ATGL's enzymatic activity is co-activated by the protein comparative gene identification-58 (CGI-58 and inhibited by the protein G0/G1 switch gene 2 (G0S2. The enzyme is predicted to act through a catalytic dyad (Ser47, Asp166 located within the conserved patatin domain (Ile10-Leu178. Yet, neither an experimentally determined 3D structure nor a model of ATGL is currently available, which would help to understand how CGI-58 and G0S2 modulate ATGL's activity. In this study we determined the minimal active domain of ATGL. This minimal fragment of ATGL could still be activated and inhibited by CGI-58 and G0S2, respectively. Furthermore, we show that this minimal domain is sufficient for protein-protein interaction of ATGL with its regulatory proteins. Based on these data, we generated a 3D homology model for the minimal domain. It strengthens our experimental finding that amino acids between Leu178 and Leu254 are essential for the formation of a stable protein domain related to the patatin fold. Our data provide insights into the structure-function relationship of ATGL and indicate higher structural similarities in the N-terminal halves of mammalian patatin-like phospholipase domain containing proteins, (PNPLA1, -2,- 3 and -5 than originally anticipated.

  7. The hepatitis C virus core protein inhibits adipose triglyceride lipase (ATGL)-mediated lipid mobilization and enhances the ATGL interaction with comparative gene identification 58 (CGI-58) and lipid droplets.

    Camus, Gregory; Schweiger, Martina; Herker, Eva; Harris, Charles; Kondratowicz, Andrew S; Tsou, Chia-Lin; Farese, Robert V; Herath, Kithsiri; Previs, Stephen F; Roddy, Thomas P; Pinto, Shirly; Zechner, Rudolf; Ott, Melanie

    2014-12-26

    Liver steatosis is a common health problem associated with hepatitis C virus (HCV) and an important risk factor for the development of liver fibrosis and cancer. Steatosis is caused by triglycerides (TG) accumulating in lipid droplets (LDs), cellular organelles composed of neutral lipids surrounded by a monolayer of phospholipids. The HCV nucleocapsid core localizes to the surface of LDs and induces steatosis in cultured cells and mouse livers by decreasing intracellular TG degradation (lipolysis). Here we report that core at the surface of LDs interferes with the activity of adipose triglyceride lipase (ATGL), the key lipolytic enzyme in the first step of TG breakdown. Expressing core in livers or mouse embryonic fibroblasts of ATGL(-/-) mice no longer decreases TG degradation as observed in LDs from wild-type mice, supporting the model that core reduces lipolysis by engaging ATGL. Core must localize at LDs to inhibit lipolysis, as ex vivo TG hydrolysis is impaired in purified LDs coated with core but not when free core is added to LDs. Coimmunoprecipitation experiments revealed that core does not directly interact with the ATGL complex but, unexpectedly, increased the interaction between ATGL and its activator CGI-58 as well as the recruitment of both proteins to LDs. These data link the anti-lipolytic activity of the HCV core protein with altered ATGL binding to CGI-58 and the enhanced association of both proteins with LDs. PMID:25381252

  8. Control of Adipose Triglyceride Lipase Action by Serine 517 of Perilipin A Globally Regulates Protein Kinase A-stimulated Lipolysis in Adipocytes

    Phosphorylation of the lipid droplet-associated protein perilipin A (Peri A) mediates the actions of cyclic AMP-dependent protein kinase A (PKA) to stimulate triglyceride hydrolysis (lipolysis) in adipocytes. Studies addressing how Peri A PKA sites regulate adipocyte lipolysis have relied on non-ad...

  9. Triglyceride selectivity of immobilized Thermomyces lanuginosa lipase in interesterification

    Rønne, Torben Harald; Pedersen, Lars S.; Xu, Xuebing

    2005-01-01

    The triglyceride (fatty acid) selectivity of an immobilized lipase from Thermomyces lanuginosa (Lipozyme TL IM) was investigated in lipase-catalyzed interesterification reactions between two mono-acid TG in n-hexane. Tristearin (tri-C18:0) was used as a reference in a series of TG with saturated FA......-C16:0) and trilaurin (tri-C12:0) in n-hexane. An increase in temperature (40 to 60°C) was found to affect the reactivity of the lipase significantly. The reactivity of Lipozyme TL IM was unaffected by the change in aw from 0.1130 to 0.5289. An increase in aw only led to an increase in FFA formation....

  10. Structure of the human hepatic triglyceride lipase gene

    The structure of the human hepatic triglyceride lipase gene was determined from multiple cosmid clones. All the exons, exon-intron junctions, and 845 bp of the 5' and 254 bp of the 3' flanking DNA were sequenced. Comparison of the exon sequences to three previously published cDNA sequences revealed differences in the sequence of the codons for residue 133, 193, 202, and 234 that may represent sequence polymorphisms. By primer extension, hepatic lipase mRNA initiates at an adenine 77 bases upstream of the translation initiation site. The hepatic lipase gene spans over 60 kb containing 9 exons and 8 introns, the latter being all located within the region encoding the mature protein. The exons are all of average size (118-234 bp). Exon 1 encodes the signal peptide, exon 4, a region that binds to the lipoprotein substrate, and exon 5, an evolutionarily highly conserved region of potential catalytic function, and exons 6 and 9 encode sequences rich in basic amino acids thought to be important in anchoring the enzyme to the endothelial surface by interacting with acidic domains of the surface glycosaminoglycans. The human lipoprotein lipase gene has been recently reported to have an identical exon-intron organization containing the analogous structural domains. The observations strongly support the common evolutionary origin of these two lipolytic enzymes

  11. Interaction between the triglyceride lipase ATGL and the arf1 activator GBF1

    Ellong, Emy Njoh

    2011-07-18

    The Arf1 exchange factor GBF1 (Golgi Brefeldin A resistance factor 1) and its effector COPI are required for delivery of ATGL (adipose triglyceride lipase) to lipid droplets (LDs). Using yeast two hybrid, co-immunoprecipitation in mammalian cells and direct protein binding approaches, we report here that GBF1 and ATGL interact directly and in cells, through multiple contact sites on each protein. The C-terminal region of ATGL interacts with N-terminal domains of GBF1, including the catalytic Sec7 domain, but not with full-length GBF1 or its entire N-terminus. The N-terminal lipase domain of ATGL (called the patatin domain) interacts with two C-terminal domains of GBF1, HDS (Homology downstream of Sec7) 1 and HDS2. These two domains of GBF1 localize to lipid droplets when expressed alone in cells, but not to the Golgi, unlike the full-length GBF1 protein, which localizes to both. We suggest that interaction of GBF1 with ATGL may be involved in the membrane trafficking pathway mediated by GBF1, Arf1 and COPI that contributes to the localization of ATGL to lipid droplets.

  12. Rhizomucor miehei triglyceride lipase is processed and secreted from transformed Aspergillus oryzae.

    Huge-Jensen, B; Andreasen, F; Christensen, T; Christensen, M; Thim, L; Boel, E

    1989-09-01

    The cDNA encoding the precursor of the Rhizomucor miehei triglyceride lipase was inserted in an Aspergillus oryzae expression vector. In this vector the expression of the lipase cDNA is under control of the Aspergillus oryzae alpha-amylase gene promoter and the Aspergillus niger glucoamylase gene terminator. The recombinant plasmid was introduced into Aspergillus oryzae, and transformed colonies were selected and screened for lipase expression. Lipase-positive transformants were grown in a small fermentor, and recombinant triglyceride lipase was purified from the culture broth. The purified enzymatically active recombinant lipase (rRML) secreted from A. oryzae was shown to have the same characteristics with respect to mobility on reducing SDS-gels and amino acid composition as the native enzyme. N-terminal amino acid sequencing indicated that approximately 70% of the secreted rRML had the same N-terminal sequence as the native Rhizomucor miehei enzyme, whereas 30% of the secreted rRML was one amino acid residue shorter in the N-terminal. The recombinant lipase precursor, which has a 70 amino acid propeptide, is thus processed in and secreted from Aspergillus oryzae. We have hereby demonstrated the utility of this organism as a host for the production of recombinant triglyceride lipases. PMID:2586234

  13. Lapacho tea (Tabebuia impetiginosa) extract inhibits pancreatic lipase and delays postprandial triglyceride increase in rats.

    Kiage-Mokua, Beatrice Nyanchama; Roos, Nils; Schrezenmeir, Jürgen

    2012-12-01

    Earlier work in our laboratory indicated that ethanolic extracts of Tabebuia impetiginosa, Arctium lappa L., Calendula officinalis, Helianthus annuus, Linum usitatissimum and L. propolis, inhibit pancreatic lipase in vitro. In a follow-up study we assessed their effects on plasma triglycerides in rats fed on a fatty meal. Extracts, orlistat or only ethanol were given orally to the rats together with the test meal and the rate of increase of postprandial triglycerides was assessed over 4 h. Clearing of the triglycerides from the blood compartment was abolished by inhibiting lipoprotein lipase with Triton WR-1339. Our results showed that out of all the extracts, the bark of Tabebuia impetiginosa led to a significant delay in the postprandial increase of plasma triglycerides. However, lapachol, which is contained in the bark of Tabebuia impetiginosa and soluble in ethanol, had no lipase inhibitory effect in vitro and hence this substance did not seem to mediate the pertinent effect. PMID:22431070

  14. Monoolein production by triglycerides hydrolysis using immobilized Rhizopus oryzae lipase.

    Ghattas, Nesrine; Abidi, Ferid; Galai, Said; Marzouki, M Nejib; Salah, Abderraouf Ben

    2014-07-01

    Lipase extracted from Rhizopus oryzae was immobilized in alginate gel beads. The effects of the immobilization conditions, such as, alginate concentration, CaCl2 concentration and amount of initial enzyme on retained activity (specific activity ratio of entrapped active lipase to free lipase) were investigated. The optimal conditions for lipase entrapment were determined: 2% (w/v) alginate concentration, 100mM CaCl2 and enzyme ratio of 2000IU/mL.In such conditions, immobilized lipase by inclusion in alginate showed a highest stability and activity, on olive oil hydrolysis reaction where it could be reused for 10 cycles. After 15min of hydrolysis reaction, the mass composition of monoolein, diolein and triolein were about 78%, 10% and 12%. Hydrolysis' products purification by column chromatography lead to a successful separation of reaction compounds and provide a pure fraction of monoolein which is considered as the widest used emulsifier in food and pharmaceutical industries. PMID:24755261

  15. Regulation of Triglyceride Metabolism. IV. Hormonal regulation of lipolysis in adipose tissue

    Jaworski, Kathy; Sarkadi-Nagy, Eszter; Duncan, Robin E.; Ahmadian, Maryam; Sul, Hei Sook

    2007-01-01

    Triacylglycerol (TAG) stored in adipose tissue can be rapidly mobilized by the hydrolytic action of lipases, with the release of fatty acids (FA) that are used by other tissues during times of energy deprivation. Unlike synthesis of TAG, which occurs not only in adipose tissue but also in other tissues such as liver for very-low-density lipoprotein formation, hydrolysis of TAG, lipolysis, predominantly occurs in adipose tissue. Until recently, hormone-sensitive lipase was considered to be the...

  16. FGF21 Lowers Plasma Triglycerides by Accelerating Lipoprotein Catabolism in White and Brown Adipose Tissues.

    Schlein, Christian; Talukdar, Saswata; Heine, Markus; Fischer, Alexander W; Krott, Lucia M; Nilsson, Stefan K; Brenner, Martin B; Heeren, Joerg; Scheja, Ludger

    2016-03-01

    FGF21 decreases plasma triglycerides (TGs) in rodents and humans; however, the underlying mechanism or mechanisms are unclear. In the present study, we examined the role of FGF21 in production and disposal of TG-rich lipoproteins (TRLs) in mice. Treatment with pharmacological doses of FGF21 acutely reduced plasma non-esterified fatty acids (NEFAs), liver TG content, and VLDL-TG secretion. In addition, metabolic turnover studies revealed that FGF21 facilitated the catabolism of TRL in white adipose tissue (WAT) and brown adipose tissue (BAT). FGF21-dependent TRL processing was strongly attenuated in CD36-deficient mice and transgenic mice lacking lipoprotein lipase in adipose tissues. Insulin resistance in diet-induced obese and ob/ob mice shifted FGF21 responses from WAT toward energy-combusting BAT. In conclusion, FGF21 lowers plasma TGs through a dual mechanism: first, by reducing NEFA plasma levels and consequently hepatic VLDL lipidation and, second, by increasing CD36 and LPL-dependent TRL disposal in WAT and BAT. PMID:26853749

  17. Triglyceride kinetics, tissue lipoprotein lipase, and liver lipogenesis in septic rats

    Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical College, Philadelphia, PA (USA))

    1990-04-01

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studied by examining liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant iv infusion of (2-3H)glycerol-labeled VLDL. Clearance of VLDL-TG was also evaluated by measuring activities of lipoprotein lipase (LPL) in heart, soleus muscle, and adipose tissue from fasted control, fasted E. coli-treated, fed control, and fed E. coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 x 10(7) live E. coli colonies per 100 g body wt. Twenty-four hours after E. coli injection, serum TG, free fatty acids (FFA), and cholesterol of fasted E. coli-treated rats were elevated by 170, 76, and 16%, respectively. The elevation of serum TG may be attributed to the 67% decrease in clearance rate of VLDL-TG in fasted E. coli-treated rats compared with their fasted controls. The suppressed activities of LPL in adipose tissue, skeletal muscle, and heart were consistent with reduced clearance of TG. Secretion of VLDL-TG declined by 31% in livers of fasted E. coli-treated rats, which was accompanied by a twofold increase in the composition of liver TG. Rates of in vivo TG synthesis in livers of the fasted E. coli-treated rats were twofold higher than in those of fasted control rats. Decreased rate of TG appearance along with the increase in liver synthesis of TG contributed to the elevation of liver lipids in the fasted E. coli-treated rats.

  18. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei;

    2015-01-01

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study...... cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but...

  19. The role of triglyceride lipases in cancer associated cachexia

    Das, Suman K.; Hoefler, Gerald

    2013-01-01

    Cancer associated cachexia (CAC) is a complex multiorgan syndrome frequently associated with various forms of cancer. Affected patients suffer from a dramatic loss of skeletal muscle and adipose tissue. Most cases are accompanied by anorexia, and nutritional supplements are not sufficient to stop or reverse its course. CAC impairs many forms of therapeutic interventions and accounts for 15–20% of all deaths of cancer patients. Recently, several studies have recognized the importance of lipid ...

  20. Use of a fluorescent radiolabeled triacylglycerol as a substrate for lipoprotein lipase and hepatic triglyceride lipase

    A fluorescent radiolabeled triacylglycerol has been synthesized by using a fluorescent fatty acid (pyrene decanoic acid) and a radiolabeled oleic acid. This analog of the natural substrate, 1(3)pyrene decanoic-2,3 (1,2)-dioleoyl-sn-glycerol, has been tested as substrate for determining lipoprotein lipase and hepatic triacylglycerol lipase activities in post-heparin plasma. Optimal conditions for the determination of the two post-heparin plasma lipases were similar to those using radiolabeled triolein. Using this substrate, both post-heparin lipases exhibited their characteristic properties (pH optimum and effect of inhibitors) and attacked external ester bonds (1 or 3) containing pyrene decanoic and oleic acids at a similar rate

  1. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-01-01

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1–coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf–GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD...

  2. Removal of intra-abdominal visceral adipose tissue improves glucose tolerance in rats: role of hepatic triglyceride storage.

    Foster, Michelle T; Shi, Haifei; Seeley, Randy J; Woods, Stephen C

    2011-10-24

    Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-visceral adipose depots since the latter drains into systemic but not portal circulation. To assess this we surgically decreased visceral white adipose tissue (~0.5 g VWATx) and compared the effects to removal of non-visceral epididymal fat (~4 g; EWATx), combination removal of visceral and non-visceral fat (~4.5 g; EWATx/VWATx) and sham-operated controls, in chow-fed rats. At 8 weeks after surgery, only the groups with visceral fat removed had a significantly improved glucose tolerance, although 8 times more fat was removed in EWATx compared with VWATx. This suggests that mechanisms controlling glucose metabolism are relatively more sensitive to reductions in visceral adipose tissue mass. Groups with visceral fat removed also had significantly decreased hepatic lipoprotein lipase (LPL) and triglyceride content compared with controls, while carnitine palmitoyltransferase (CPT-1A) was decreased in all fat-removal groups. In a preliminary experiment, we assessed the opposite hypothesis; i.e., we transplanted excess visceral fat from a donor rat to the visceral cavity (omentum and mesentery), which drains into the hepatic portal vein, of a recipient rat but observed no major metabolic effect. Overall, our results indicate surgical removal of intra-abdominal fat improves glucose tolerance through mechanism that may be mediated by reductions in liver triglyceride. PMID:21683727

  3. Carboxyl Ester Lipase from Either Mother’s Milk or the Pancreas Is Required for Efficient Dietary Triglyceride Digestion in Suckling Mice1,2

    Miller, Rita; Lowe, Mark E.

    2008-01-01

    Because dietary fats provide an important source of energy in the newborn, the efficient digestion of dietary fats is critical to their well-being. Despite the importance of dietary fat digestion, newborns have a deficiency of pancreatic triglyceride lipase, the predominant digestive lipase in adults. The efficient dietary fat digestion in newborns suggests that other lipases must compensate for the lack of pancreatic triglyceride lipase. In this study, we test the hypothesis that breast milk...

  4. Fatty acid composition of adipose tissue triglycerides after weight loss and weight maintenance

    Kunešová, M; Hlavatý, P; Tvrzická, E;

    2012-01-01

    Fatty acid composition of adipose tissue changes with weight loss. Palmitoleic acid as a possible marker of endogenous lipogenesis or its functions as a lipokine are under debate. Objective was to assess the predictive role of adipose triglycerides fatty acids in weight maintenance in participants...... of the DIOGENES dietary intervention study. After an 8-week low calorie diet (LCD) subjects with > 8 % weight loss were randomized to 5 ad libitum weight maintenance diets for 6 months: low protein (P)/low glycemic index (GI) (LP/LGI), low P/high GI (LP/HGI), high P/low GI (HP/LGI), high P/high GI...... (HP/HGI), and a control diet. Fatty acid composition in adipose tissue triglycerides was determined by gas chromatography in 195 subjects before the LCD (baseline), after LCD and weight maintenance. Weight change after the maintenance phase was positively correlated with baseline adipose palmitoleic...

  5. Medium-Chain Triglyceride Activated Brown Adipose Tissue and Induced Reduction of Fat Mass in C57BL/6J Mice Fed High-fat Diet

    ZHANG Yong; XUE Chang Yong; XU Qing; LIU Ying Hua; ZHANG Xin Sheng; WANG Jin; YU Xiao Ming; ZHANG Rong Xin; XUE Chao; YANG Xue Yan

    2015-01-01

    Objective To investigate activation of brown adipose tissue (BAT) stimulated by medium-chain triglyceride (MCT). Methods 30 Male C57BL/6J obese mice induced by fed high fat diet (HFD) were divided into 2 groups, and fed another HFD with 2% MCT or long-chain triglyceride (LCT) respectively for 12 weeks. Body weight, blood biochemical variables, interscapular brown fat tissue (IBAT) mass, expressions of mRNA and protein of beta 3-adrenergic receptors (β3-AR), uncoupling protein-1 (UCP1), hormone sensitive lipase (HSL), protein kinase A (PKA), and adipose triglyceride lipase (ATGL) in IBAT were measured. Results Significant decrease in body weight and body fat mass was observed in MCT group as compared with LCT group (P<0.05) after 12 weeks. Greater increases in IBAT mass was observed in MCT group than in LCT group (P<0.05). Blood TG, TC, LDL-C in MCT group were decreased significantly, meanwhile blood HDL-C, ratio of HDL-C/LDL-C and norepinephrine were increased markedly. Expressions of mRNA and protein ofβ3-AR, UCP1, PKA, HSL, ATGL in BAT were greater in MCT group than in LCT group (P<0.05). Conclusion Our results suggest that MCT stimulated the activation of BAT, possible via norepinephrine pathway, which might partially contribute to reduction of the body fat mass in obese mice fed high fat diet.

  6. ELMOD2 is anchored to lipid droplets by palmitoylation and regulates adipocyte triglyceride lipase recruitment.

    Suzuki, Michitaka; Murakami, Tatsuro; Cheng, Jinglei; Kano, Hiroyuki; Fukata, Masaki; Fujimoto, Toyoshi

    2015-06-15

    Adipocyte triglyceride lipase (ATGL) is the major enzyme involved in the hydrolysis of triglycerides. The Arf1-coat protein complex I (COPI) machinery is known to be engaged in the recruitment of ATGL to lipid droplets (LDs), but the regulatory mechanism has not been clarified. In the present study, we found that ELMOD2, a putative noncanonical Arf-GTPase activating protein (GAP) localizing in LDs, plays an important role in controlling ATGL transport to LDs. We showed that knockdown of ELMOD2 by RNA interference induced an increase in the amount of ATGL existing in LDs and decreased the total cellular triglycerides. These effects of ELMOD2 knockdown were canceled by transfection of small interfering RNA-resistant cDNA of wild-type ELMOD2 but not by that of mutated ELMOD2 lacking the Arf-GAP activity. ELMOD2 was distributed in the endoplasmic reticulum and mitochondria as well as in LDs, but palmitoylation was required only for distribution to LDs. An ELMOD2 mutant deficient in palmitoylation failed to reconstitute the ATGL transport after the ELMOD2 knockdown, indicating that distribution in LDs is indispensable to the functionality of ELMOD2. These results indicate that ELMOD2 regulates ATGL transport and cellular lipid metabolism by modulating the Arf1-COPI activity in LDs. PMID:25904333

  7. Effects of Rosiglitazone and High Fat Diet on Lipase/Esterase Expression in Adipose Tissue

    Shen, Wen‐Jun; Patel, Shailja; Yu, Zaixin; Jue, Dyron; Kraemer, Fredric B.

    2006-01-01

    A number of intracellular lipase/esterase have been reported in adipose tissue either by functional assays of activity or through proteomic analysis. In the current work, we have studied the relative expression level of 12 members of the lipase/esterase family that are found in white adipose tissue. We found that the relative mRNA levels of ATGL and HSL are the most abundant, being 2–3 fold greater than TGH or ADPN; whereas other intracellular neutral lipase/esterases were expressed at substa...

  8. A micromethod for assay of lipoprotein lipase activity in needle biopsy samples of human adipose tissue and skeletal muscle

    A rapid and simple procedure for assay of lipoprotein lipase (LPL) activity in small amounts of human adipose tissue and skeletal muscle is described and validated. The enzyme is eluted from tissues with heparin and the activity is determined from the eluate by measuring the release of [14C]oleic acid from a gum arabic stabilized emulsion of glycerol-tri[14C]oleate in a Tris-buffer medium containing albumin and pooled normal human serum. Reproducible results are obtained with amounts of tissue ranging from 2 to 25 mg. The Ksub(m) values of the adipose tissue and skeletal muscle LPL for the triolein substrate were 0.74 +- 0.06 and 0.77 +- 0.05 mmol/l, respectively. The standard radioactive triolein emulsion was hydrolyzed by adipose tissue LPL at a rate closely similar to rat VLDL-triglyceride labeled in vivo with [1-14C]palmitic acid, suggesting that the experimental substrate behaved in a similar manner to the natural substrate. The LPL activity was much higher in adipose tissue than in muscle. In adipose tissue the LPL activity was 2-4 times higher in women than in men whereas no sex difference was present in the LPL activity of muscle. (Auth.)

  9. Triglyceride-lowering effect of respiratory uncoupling in white adipose tissue

    Rossmeisl, Martin; Kovář, J.; Syrový, Ivo; Flachs, Pavel; Bobková, D.; Kolář, František; Poledne, R.; Kopecký, Jan

    2005-01-01

    Roč. 13, č. 5 (2005), s. 835-844. ISSN 1071-7323 R&D Projects: GA ČR(CZ) GP303/03/P127; GA ČR(CZ) GA303/02/1220 Institutional research plan: CEZ:AV0Z5011922 Keywords : adipose tissue * uncoupling protein * lipoprotein lipase Subject RIV: FB - Endocrinology, Diabetology, Metabolism, Nutrition Impact factor: 3.972, year: 2005

  10. Modeling the methanolysis of triglyceride catalyzed by immobilized lipase in a continuous-flow packed-bed reactor

    Highlights: • A Burkholderia lipase was immobilized on alkyl-grafted celite carriers. • Celite-alkyl-lipase catalyzed the methanolysis of triglyceride in packed-bed reactor. • The kinetics of the enzymatic transesterification follows Ping Pong Bi Bi mechanism. • Models were developed to discuss the mass transfer and enzyme kinetics in the PBR. - Abstract: A Burkholderia lipase was immobilized on celite grafted with long alkyl groups. The immobilized lipase-catalyzed methanolysis of sunflower oil in a packed-bed reactor (PBR) follows the Ping Pong Bi Bi mechanism. The external mass transfer and enzymatic reaction that simultaneously occurred in the PBR were investigated via the mathematical models. The overall biodiesel production in the PBR was verified to work in an enzymatic reaction-limited regime. Triglyceride conversion and biodiesel yield were higher under a lower reactant feeding rate, while a larger amount of biocatalyst would be required to achieve the designated conversion rate if a higher reactant feeding rate was employed. The PBR can achieve nearly complete conversion of triglyceride at a biocatalyst bed height of 60 cm (ca. 29 g biocatalyst) and a flow rate of 0.1 ml min−1, whereas the biodiesel yield was lower than 67%, probably due to the positional specificity of Burkholderia lipase and the accumulation of glycerol

  11. Emulsifying triglycerides with dairy phospholipids instead of soy lecithin modulates gut lipase activity

    Mathiassen, Jakob Hovalt; Nejrup, Rikke Guldhammer; Frøkiær, Hanne;

    2015-01-01

    hydrolytic rate of gastric lipase and pancreatic lipase, on their own or pancreatic lipase after gastric lipase on TAG droplets of similar size emulsified in either soy lecithin (SL) or in bovine milk phospholipids (MPL), more similar to human milk globule membrane lipids than soy lecithin. Gastric lipase...... activity was substantially higher on MPL-emulsified particles, while SL emulsification caused a higher rate of pancreatic lipase hydrolysis, on particles that had not been pre-treated with gastric lipase. MPL emulsification did however cause higher pancreatic lipase activity, when the particles had been...... pre-treated with gastric lipase. The attenuating effect of MPL-emulsification on pancreas lipase activity was validated in vivo in mice. Practical application: Our results show that the activity of gastric lipase, a key enzyme in lipid absorption in neonates, is highly dependent on the phospholipid...

  12. Angiotensin II Reduces Lipoprotein Lipase Expression in Visceral Adipose Tissue via Phospholipase C β4 Depending on Feeding but Increases Lipoprotein Lipase Expression in Subcutaneous Adipose Tissue via c-Src.

    Tsuyoshi Uchiyama

    Full Text Available Metabolic syndrome is characterized by visceral adiposity, insulin resistance, high triglyceride (TG- and low high-density lipoprotein cholesterol-levels, hypertension, and diabetes-all of which often cause cardiovascular and cerebrovascular diseases. It remains unclear, however, why visceral adiposity but not subcutaneous adiposity causes insulin resistance and other pathological situations. Lipoprotein lipase (LPL catalyzes hydrolysis of TG in plasma lipoproteins. In the present study, we investigated whether the effects of angiotensin II (AngII on TG metabolism are mediated through an effect on LPL expression. Adipose tissues were divided into visceral adipose tissue (VAT and subcutaneous adipose tissue (SAT for comparison. AngII accelerated LPL expression in SAT but, on the contrary, suppressed its expression in VAT. In both SAT and VAT, AngII signaled through the same type 1 receptor. In SAT, AngII increased LPL expression via c-Src and p38 MAPK signaling. In VAT, however, AngII reduced LPL expression via the Gq class of G proteins and the subsequent phospholipase C β4 (PLCβ4, protein kinase C β1, nuclear factor κB, and inducible nitric oxide synthase signaling pathways. PLCβ4 small interfering RNA experiments showed that PLCβ4 expression is important for the AngII-induced LPL reduction in VAT, in which PLCβ4 expression increases in the evening and falls at night. Interestingly, PLCβ4 expression in VAT decreased with fasting, while AngII did not decrease LPL expression in VAT in a fasting state. In conclusion, AngII reduces LPL expression through PLCβ4, the expression of which is regulated by feeding in VAT, whereas AngII increases LPL expression in SAT. The different effects of AngII on LPL expression and, hence, TG metabolism in VAT and SAT may partly explain their different contributions to the development of metabolic syndrome.

  13. Adipose Co-expression networks across Finns and Mexicans identify novel triglyceride-associated genes

    Haas Blake E

    2012-12-01

    Full Text Available Abstract Background High serum triglyceride (TG levels is an established risk factor for coronary heart disease (CHD. Fat is stored in the form of TGs in human adipose tissue. We hypothesized that gene co-expression networks in human adipose tissue may be correlated with serum TG levels and help reveal novel genes involved in TG regulation. Methods Gene co-expression networks were constructed from two Finnish and one Mexican study sample using the blockwiseModules R function in Weighted Gene Co-expression Network Analysis (WGCNA. Overlap between TG-associated networks from each of the three study samples were calculated using a Fisher’s Exact test. Gene ontology was used to determine known pathways enriched in each TG-associated network. Results We measured gene expression in adipose samples from two Finnish and one Mexican study sample. In each study sample, we observed a gene co-expression network that was significantly associated with serum TG levels. The TG modules observed in Finns and Mexicans significantly overlapped and shared 34 genes. Seven of the 34 genes (ARHGAP30, CCR1, CXCL16, FERMT3, HCST, RNASET2, SELPG were identified as the key hub genes of all three TG modules. Furthermore, two of the 34 genes (ARHGAP9, LST1 reside in previous TG GWAS regions, suggesting them as the regional candidates underlying the GWAS signals. Conclusions This study presents a novel adipose gene co-expression network with 34 genes significantly correlated with serum TG across populations.

  14. Highly efficient extraction and lipase-catalyzed transesterification of triglycerides from Chlorella sp. KR-1 for production of biodiesel.

    Lee, Ok Kyung; Kim, Young Hyun; Na, Jeong-Geol; Oh, You-Kwan; Lee, Eun Yeol

    2013-11-01

    We developed a method for the highly efficient lipid extraction and lipase-catalyzed transesterification of triglyceride from Chlorella sp. KR-1 using dimethyl carbonate (DMC). Almost all of the total lipids, approximately 38.9% (w/w) of microalgae dry weight, were extracted from the dried microalgae biomass using a DMC and methanol mixture (7:3 (v/v)). The extracted triglycerides were transesterified into fatty acid methyl esters (FAMEs) using Novozyme 435 as the biocatalyst in DMC. Herein, DMC was used as the reaction medium and acyl acceptor. The reaction conditions were optimized and the FAMEs yield was 293.82 mg FAMEs/g biomass in 6 h of reaction time at 60 °C in the presence of 0.2% (v/v) water. Novozyme 435 was reused more than ten times while maintaining relative FAMEs conversion that was greater than 90% of the initial FAMEs conversion. PMID:23999257

  15. Apolipoprotein AV Accelerates Plasma Hydrolysis OfTriglyceride-Rich Lipoproteins By Interaction With Proteoglycan BoundLipoprotein Lipase

    Merkel, Martin; Loeffler, Britta; Kluger, Malte; Fabig, Nathalie; Geppert, Gesa; Pennacchio, Len A.; Laatsch, Alexander; Heeren, Joerg

    2005-02-22

    Apolipoprotein A5 (APOA5) is associated with differences intriglyceride levels and familial combined hyperlipidemia. In genetically engineered mice, apoAV plasma levels are inversely correlated with plasmatriglycerides. To elucidate the mechanism by which apoAV influences plasma triglycerides, metabolic studies and in vitro assays resembling physiological conditions were performed. In hAPOA5 transgenic mice(hAPOA5tr), catabolism of chylomicrons and VLDL was accelerated due to a faster plasma hydrolysis of triglycerides by lipoprotein lipase (LPL).Hepatic VLDL and intestinal chylomicron production were not affected. The functional interplay between apoAV and LPL was further investigated by crossbreeding a human LPL transgene with the apoa5 knockout, and the hAPOA5tr to an LPL deficient background. Increased LPL activity completely normalized hypertriglyceridemia of apoa5 deficient mice,however, over expression of human apoAV modulated triglyceride levels only slightly when LPL was reduced. To reflect the physiological situation in which LPL is bound to cell surface proteoglycans, we examined hydrolysis in the presence or absence of proteoglycans. Without proteoglycans, apoAV derived either from triglyceride-rich lipoproteins, hAPOA5tr HDL, or a recombinant source did not alter the LPL hydrolysis rate. In the presence of proteoglycans, however, apoAV led to a significant and dose-dependent increase in LPL mediated hydrolysis of VLDL triglycerides. These results were confirmed in cell culture using a proteoglycan-deficient cell line.A direct interaction between LPL and apoAV was found by ligand blotting.It is proposed, that apoAV reduces triglyceride levels by guiding VLDL and chylomicrons to proteoglycans bound LPL for lipolysis.

  16. Changes in lipoprotein lipase activity in the adipose tissue, heart and liver of continuously irradiated rats

    Adult male Wistar rats were continuously irradiated for 30 days on an experimental field from a 60Co source of radiation. Lipoprotein lipase activity was determined in their adipose tissue, heart and liver at intervals of 1, 3, 7, 14, 21 and 30 days from the beginning of irradiation and triacylglycerol, total cholesterol, phospholipid and non-esterified fatty acid concentrations were determined in their serum. Throughout the whole of the study, lipoprotein lipase activity was lower in the adipose tissue and higher in the heart of irradiated rats than in the controls. In the liver it was low 3 days from the onset of irradiation; at the other intervals it was variable and differed only non-significantly from the controls. Serum lipid concentrations were raised in irradiated rats - triacylglycerol from the 7th day, phospholipids from the 14th day and non-esterified fatty acids throughout the whole period of irradiation. In keeping with the high triacylglycerol values in the serum of irradiated rats, lipoprotein lipase activity in their adipose tissue was low. (author)

  17. Metabolism of apolipoproteins B-48 and B-100 of triglyceride-rich lipoproteins in normal and lipoprotein lipase-deficient humans.

    Stalenhoef, A.F.; Malloy, M J; Kane, J P; Havel, R J

    1984-01-01

    The metabolism of apolipoproteins B-48 and B-100 (apo B-48 and B-100) in large triglyceride-rich lipoproteins (300 to 1500 A in diameter) has been compared in three normal subjects and two subjects with genetically determined deficiency of lipoprotein lipase. The triglyceride-rich lipoproteins were obtained from a lipoprotein lipase-deficient donor 4 hr after a fat-rich meal in order to obtain chylomicrons (containing apo B-48) and very low density lipoproteins (VLDL) (containing apo B-100), ...

  18. Lipase

    Lipase is a digestive enzyme that is found in many plants, animals, bacteria, and molds. An enzyme ... particular biochemical reaction in the body. People use lipase as a medicine. Lipase is used for indigestion, ...

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

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

    2011-01-01

    both SCAAT and SCFAT. 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...... abdominal (SCAAT) 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......, young men with IUGR 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...

  20. The effect of exercise training on hormone-sensitive lipase in rat intra-abdominal adipose tissue and muscle

    Enevoldsen, L H; Stallknecht, B; Langfort, J;

    2001-01-01

    1. Adrenaline-stimulated lipolysis in adipose tissue may increase with training. The rate-limiting step in adipose tissue lipolysis is catalysed by the enzyme hormone-sensitive lipase (HSL). We studied the effect of exercise training on the activity of the total and the activated form of HSL......, referred to as HSL (DG) and HSL (TG), respectively, and on the concentration of HSL protein in retroperitoneal (RE) and mesenteric (ME) adipose tissue, and in the extensor digitorum longus (EDL) and soleus muscles in rats. 2. Rats (weighing 96 +/- 1 g, mean +/- S.E.M.) were either swim trained (T, 18 weeks......, n = 12) or sedentary (S, n = 12). Then RE and ME adipose tissue and the EDL and soleus muscles were incubated for 20 min with 4.4 microM adrenaline. 3. HSL enzyme activities in adipose tissue were higher in T compared with S rats. Furthermore, in RE adipose tissue, training also doubled HSL protein...

  1. Expression of human hormone-sensitive lipase in white adipose tissue of transgenic mice increases lipase activity but does not enhance in vitro lipolysis.

    Lucas, Stéphanie; Tavernier, Geneviève; Tiraby, Claire; Mairal, Aline; Langin, Dominique

    2003-01-01

    Hormone-sensitive lipase (HSL) catalyzes the hydrolysis of acylglycerols and cholesteryl esters (CEs). The enzyme is highly expressed in adipose tissues (ATs), where it is thought to play an important role in fat mobilization. The purpose of the present work was to study the effect of a physiological increase of HSL expression in vivo. Transgenic mice were produced with a 21 kb human genomic fragment encompassing the exons encoding the adipocyte form of HSL. hHSL mRNA was expressed at 3-fold higher levels than murine HSL mRNA in white adipocytes. Transgene expression was also observed in brown adipose tissue (BAT) and skeletal muscle. The human protein was detected in ATs of transgenic (Tg) mice. The hydrolytic activities against triacylglycerol (TG), diacylglycerol (DG) analog, and CE were increased in transgenic mouse AT. However, cAMP-inducible adipocyte lipolysis was lower in transgenic animals. In the B6CBA genetic background, transgenic mice up to 14 weeks of age showed lower body weight and fat mass. The phenotype was not observed in older animals and in mice fed a high-fat diet (HFD). In the OF1 genetic background, there was no difference in fat mass of mice fed ad libitum. However, transgenic mice became leaner than their wild-type (WT) littermates after a 4 day calorie restriction. The data show that overexpression of HSL, despite increased lipase activity, does not lead to enhanced lipolysis. PMID:12518034

  2. Combined analysis of six lipoprotein lipase genetic variants on triglycerides, high-density lipoprotein, and ischemic heart disease: cross-sectional, prospective, and case-control studies from the Copenhagen City Heart Study

    Wittrup, HH; Andersen, RV; Tybjærg-Hansen, Anne;

    2006-01-01

    lipase genotypes on triglycerides, HDL, and IHD. DESIGN: The cross-sectional study involved 9004 adults. The prospective study consisted of 8817 adults developing 1001 IHD events over 23 yr. The case-control study involved 7818 non-IHD individuals vs. cohorts of 915 and 1062 IHD patients, respectively...

  3. Adipose Overexpression of Desnutrin Promotes Fatty Acid Use and Attenuates Diet-Induced Obesity

    Ahmadian, Maryam; Duncan, Robin E.; Varady, Krista A.; Frasson, Danubia; Hellerstein, Marc K.; Birkenfeld, Andreas L.; Samuel, Varman T.; Shulman, Gerald I.; Wang, Yuhui; Kang, Chulho; Sul, Hei Sook

    2009-01-01

    OBJECTIVE To investigate the role of desnutrin in adipose tissue triacylglycerol (TAG) and fatty acid metabolism. RESEARCH DESIGN AND METHODS We generated transgenic mice overexpressing desnutrin (also called adipose triglyceride lipase [ATGL]) in adipocytes (aP2-desnutrin) and also performed adenoviral-mediated overexpression of desnutrin in 3T3-L1CARΔ1 adipocytes. RESULTS aP2-desnutrin mice were leaner with decreased adipose tissue TAG content and smaller adipocyte size. Overexpression of d...

  4. Hormone-sensitive lipase (HSL) expression and regulation in skeletal muscle

    Langfort, J; Ploug, T; Ihlemann, J;

    1998-01-01

    Because the enzymatic regulation of muscle triglyceride metabolism is poorly understood we explored the character and activation of neutral lipase in muscle. Western blotting of isolated rat muscle fibers demonstrated expression of hormone-sensitive lipase (HSL). In incubated soleus muscle epinep...... studies have shown that HSL is present in skeletal muscle cells and is stimulated in parallel with glycogen phosphorylase by both epinephrine and contractions. HSL adapts differently to training in muscle compared with adipose tissue....

  5. Effect of di(2-ethylhexyl) phthalate (DEHP) on lipolysis and lipoprotein lipase activities in adipose tissue of rats.

    Martinelli, Marcela I; Mocchiutti, Norberto O; Bernal, Claudio A

    2010-09-01

    The di(2-ethylhexyl) phthalate (DEHP) is an ubiquitous environmental chemical with detrimental health effects. The present work was designed to asses some potential mechanisms by which DEHP causes, among others, a reduced body fat retention. Since this effect could be related to an alteration of adipocyte triacylglycerol (TG) metabolism, we evaluated the effects of dietary DEHP in adipose tissues upon (1) the number and size of fat cells; (2) the basal and stimulated lipolysis and (3) the lipoprotein lipase (LPL) activity. Groups of male Wistar rats were fed for 21 days a control diet alone (control group) or the same control diet supplemented with 2% (w/w) of DEHP (DEHP group). The LPL activity of DEHP-fed rats was increased in lumbar and epididymal adipose tissues. These rats had significantly reduced weight in epididymal and lumbar tissues, together with reduced size of epididymal adipocytes. These alterations do not seem to be associated with higher lipid mobility because neither basal lipolysis nor 'in vitro' stimulated lipolysis by noradrenaline (NA) showed to be modified by DEHP. Based on these results, we concluded that the adipose tissue size reduction induced by DEHP intake is not due to changes in lipolysis nor to a decreased LPL activity. More research is needed to achieve a comprehensive understanding of the potential mechanisms by which DEHP causes, among others, a reduced body fat retention. PMID:20144957

  6. Changes in lipoprotein lipase activity in the adipose tissue and heart of non-lethally X-irradiated rats

    After 16 h of nocturnal food deprivation, male Wistar rats were irradiated with a single whole-body dose of 2.40 Gy of X-rays. Both the irradiated and sham-irradiated (control) rats were pair-fed for the first six days after irradiation, but for the rest of the time they were fed ad libitum. Lipoprotein lipase activity (LPLA) in the adipose tissue fell between 24 and 48 h; LPLA in the heart fell at 24 h and 21 days and rose on the 14th day. The serum triacylglycerol concentration rose between 24 and 72 h. A comparison with the fed control group showed LPLA in adipose tissue to be reduced at 6 and 72 h and on the 28th day and raised between the 7th and the 14th day. In the heart it was raised at 1 h and between 72h and the 14th day, it was reduced on the 21st day and rose on the 35th day. The triacylglycerol concentration was raised between 48 and 72 h and on the 28th day. Pair-feeding after non-lethal X-irradiation allowed more exact differentiation of the specific effect of ionizing radiation on LPLA in the adipose tissue and heart at early post-irradiation intervals. (author)

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

    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. PMID:16249444

  8. Placental lipases in pregnancies complicated by gestational diabetes mellitus (GDM.

    Helen L Barrett

    Full Text Available Infants of women with gestational diabetes mellitus (GDM are more likely to be born large for gestational age with a higher percentage body fat. Elevated maternal lipids may contribute to this. Placental lipases such as lipoprotein lipase (LPL, endothelial lipase (EL and hormone sensitive lipase (HSL are involved in transferring lipids from mother to fetus. Previous studies of expression of these lipases in placentae in women with diabetes in pregnancy have reported divergent results. Intracellular lipases such as adipose triglyceride lipase (ATGL, and HSL are central to lipid droplet metabolism. The activities of these lipases are both influenced by Perilipin 1, and ATGL is also activated by a co-factor comparative gene identification-58 (CGI-58 and inhibited by G0/G1 switch gene 2 (GS02. None of these modifying factors or ATGL have been examined previously in placenta. The purpose of this study was therefore to examine the expression of ATGL, HSL, LPL, EL, as well as Perilipin 1, GS02 and CGI-58 in term pregnancies complicated by GDM. mRNA and protein expression of the lipases were measured in placentae from 17 women with GDM and 17 normoglycaemic pregnancies, matched for maternal BMI and gestational age of delivery. ATGL mRNA expression was increased and HSL mRNA expression reduced in placentae from GDM although there was no differences in protein expression of any of the lipases. All lipases were localised to trophoblasts and endothelial cells. The expression of Perilipin 1 and CGI-58 mRNA was increased and GS02 not altered in GDM. These results suggest that there is no difference in expression in these four lipases between GDM and normoglycaemic placentae, and therefore altered lipid transfer via these lipases does not contribute to large for gestational age in infants of women with GDM.

  9. Covalent immobilization of lipase, glycerol kinase, glycerol-3-phosphate oxidase & horseradish peroxidase onto plasticized polyvinyl chloride (PVC strip & its application in serum triglyceride determination

    Nidhi Chauhan

    2014-01-01

    Full Text Available Background & objectives:Reusable biostrip consisting enzymes immobilized onto alkylamine glass beads affixed on plasticized PVC strip for determination of triglyceride (TG suffers from high cost of beads and their detachments during washings for reuse, leading to loss of activity. The purpose of this study was to develop a cheaper and stable biostrip for investigation of TG levels in serum. Methods: A reusable enzyme-strip was prepared for TG determination by co-immobilizing lipase, glycerol kinase (GK, glycerol-3-phosphate oxidase (GPO and peroxidase (HRP directly onto plasticized polyvinyl chloride (PVC strip through glutaraldehyde coupling. The method was evaluated by studying its recovery, precision and reusability. Results: The enzyme-strip showed optimum activity at pH 7.0, 35 o C and a linear relationship between its activity and triolein concentration in the range 0.1 to 15 mM. The strip was used for determination of serum TG. The detection limit of the method was 0.1 mM. Analytical recovery of added triolein was 96 per cent. Within and between batch coefficients of variation (CV were 2.2 and 3.7 per cent, respectively. A good correlation (r=0.99 was found between TG values by standard enzymic colrimetric method employing free enzymes and the present method. The strip lost 50 per cent of its initial activity after its 200 uses during the span of 100 days, when stored at 4 o C. Interpretation & conclusions: The nitrating acidic treatment of plasticized PVC strip led to glutaraldehyde coupling of four enzymes used for enzymic colourimetric determination of serum TG. The strip provided 200 reuses of enzymes with only 50 per cent loss of its initial activity. The method could be used for preparation of other enzyme strips also.

  10. Radiochemical determination of lipoprotein lipase activity (LPLA) in human adipose tissue

    Lipoprotein lipase activity (LPLA) is measured in samples (20 to 100 mg) of human fatty tissue obtained by needle biopsy. The material is converted into an acetone-ether powder by defatting. 3H-labelled triolein which is suspended in glycerol, using inactive triolein, lecithin and ultrasonication, serves as a substrate concentrate, from which a substrate is prepared by adding Tris buffer, albumin and serum. The amount of oleic acid liberated from the suspended acetone-ether powder during incubation is measured by its radioactivity. 78 determinations in patients with hyperlipoproteinemia yielded a mean LPLA value of 0.606 +- 0.501 μmoles/g-1h-1. (author)

  11. Inborn errors of cytoplasmic triglyceride metabolism.

    Wu, Jiang Wei; Yang, Hao; Wang, Shu Pei; Soni, Krishnakant G; Brunel-Guitton, Catherine; Mitchell, Grant A

    2015-01-01

    Triglyceride (TG) synthesis, storage, and degradation together constitute cytoplasmic TG metabolism (CTGM). CTGM is mostly studied in adipocytes, where starting from glycerol-3-phosphate and fatty acyl (FA)-coenzyme A (CoA), TGs are synthesized then stored in cytoplasmic lipid droplets. TG hydrolysis proceeds sequentially, producing FAs and glycerol. Several reactions of CTGM can be catalyzed by more than one enzyme, creating great potential for complex tissue-specific physiology. In adipose tissue, CTGM provides FA as a systemic energy source during fasting and is related to obesity. Inborn errors and mouse models have demonstrated the importance of CTGM for non-adipose tissues, including skeletal muscle, myocardium and liver, because steatosis and dysfunction can occur. We discuss known inborn errors of CTGM, including deficiencies of: AGPAT2 (a form of generalized lipodystrophy), LPIN1 (childhood rhabdomyolysis), LPIN2 (an inflammatory condition, Majeed syndrome, described elsewhere in this issue), DGAT1 (protein loosing enteropathy), perilipin 1 (partial lipodystrophy), CGI-58 (gene ABHD5, neutral lipid storage disease (NLSD) with ichthyosis and "Jordan's anomaly" of vacuolated polymorphonuclear leukocytes), adipose triglyceride lipase (ATGL, gene PNPLA2, NLSD with myopathy, cardiomyopathy and Jordan's anomaly), hormone-sensitive lipase (HSL, gene LIPE, hypertriglyceridemia, and insulin resistance). Two inborn errors of glycerol metabolism are known: glycerol kinase (GK, causing pseudohypertriglyceridemia) and glycerol-3-phosphate dehydrogenase (GPD1, childhood hepatic steatosis). Mouse models often resemble human phenotypes but may diverge markedly. Inborn errors have been described for less than one-third of CTGM enzymes, and new phenotypes may yet be identified. PMID:25300978

  12. Removal of Intra-abdominal Visceral Adipose Tissue Improves Glucose Tolerance in Rats: Role of Hepatic Triglyceride Storage

    Foster, Michelle T.; Shi, Haifei; Seeley, Randy J.; Woods, Stephen C.

    2011-01-01

    Epidemiological studies have demonstrated a strong link between increased visceral fat and metabolic syndrome. In rodents, removal of intra-abdominal but non-visceral fat improves insulin sensitivity and glucose homeostasis, though previous studies make an imprecise comparison to human physiology because actual visceral fat was not removed. We hypothesize that nutrient release from visceral adipose tissue may have greater consequences on metabolic regulation than nutrient release from non-vis...

  13. 脂肪甘油三酯脂肪酶( ATGL)的生物学功能及调控机制%Biological Functions and Regulation of Adipose Triacylglyceride Lipase

    胡深强; 潘志雄; 王继文

    2011-01-01

    脂肪甘油三酯脂肪酶(ATGL)是近年来研究发现的启动脂肪动员的又一关键脂肪酶.ATGL能特异性地水解甘油三酯(TAG)的第一酯键,被认为是TAG水解过程的限速酶.ATGL在脂肪组织和非脂肪组织脂代谢过程中都发挥着重要作用,其活性和表达在细胞内受到转录水平、翻译后水平等调控.ATGL介导的脂解过程可能与肥胖、糖尿病、脂肪肝等代谢疾病存在关联.本文主要就ATGL的结构特征、生物学功能及其调控机制进行综述,并对今后的研究方向和应用进行了展望.%Recent studies showed that adipose triacylglyceride lipase ( ATGL) functioned as an additional key enzyme for adipose lipid mobilization. ATGL specifically hydrolyzes the first ester bond of triglycerides and is a rate-limiting enzyme in triacylglycerol hydrolysis. The wide expression of ATGL suggested its important role in lipid metabolism in various tissue and cell types. The expression and activity of ATGL are regulated at both transcriptional and posttranslational levels. ATGL are also found to associate with obesity, diabetes, hepatic steatosis, and other related metabolic disorders. We focus on the discussion of structural characteristics, expression, biological functions, and regulatory mechanism of ATGL, and prospect on its potential application in the future.

  14. Comparative Analyses of Lipoprotein Lipase, Hepatic Lipase, and Endothelial Lipase, and Their Binding Properties with Known Inhibitors

    Wang, Ziyun; Li, Shen; Sun, Lidan; Fan, Jianglin; Liu, Zhenming

    2013-01-01

    The triglyceride lipase gene subfamily plays a central role in lipid and lipoprotein metabolism. There are three members of this subfamily: lipoprotein lipase, hepatic lipase, and endothelial lipase. Although these lipases are implicated in the pathophysiology of hyperlipidemia and atherosclerosis, their structures have not been fully solved. In the current study, we established homology models of these three lipases, and carried out analysis of their activity sites. In addition, we investiga...

  15. Nitro-Oleic Acid Reduces J774A.1 Macrophage Oxidative Status and Triglyceride Mass: Involvement of Paraoxonase2 and Triglyceride Metabolizing Enzymes.

    Rosenblat, Mira; Rom, Oren; Volkova, Nina; Aviram, Michael

    2016-08-01

    Nitro-fatty acids possess anti-atherogenic properties, but their effects on macrophage oxidative status and lipid metabolism that play important roles in atherosclerosis development are unclear. This study compared the effects of nitro-oleic acid (OLA-NO2) with those of native oleic acid (OLA) on intracellular reactive oxygen species (ROS) generation, anti-oxidants and metabolism of triglycerides and cholesterol in J774A.1 macrophages. Upon incubating the cells with physiological concentrations of OLA-NO2 (0-1 µM) or with equivalent levels of OLA, ROS levels measured by 2, 7-dichlorofluorescein diacetate, decreased dose-dependently, but the anti-oxidative effects of OLA-NO2 were significantly augmented. Copper ion addition increased ROS generation in OLA treated macrophages without affecting OLA-NO2 treated cells. These effects could be attributed to elevated glutathione levels and to increased activity and expression of paraoxonase2 that were observed in OLA-NO2 vs OLA treated cells. Beneficial effects on triglyceride metabolism were noted in OLA-NO2 vs OLA treated macrophages in which cellular triglycerides were reduced due to attenuated biosynthesis and accelerated hydrolysis of triglycerides. Accordingly, OLA-NO2 treated cells demonstrated down-regulation of diacylglycerol acyltransferase1, the key enzyme in triglyceride biosynthesis, and increased expression of hormone-sensitive lipase and adipose triglyceride lipase that regulate triglyceride hydrolysis. Finally, OLA-NO2 vs OLA treatment resulted in modest but significant beneficial effects on macrophage cholesterol metabolism, reducing cholesterol biosynthesis rate and low density lipoprotein influx into the cells, while increasing high density lipoprotein-mediated cholesterol efflux from the macrophages. Collectively, compared with OLA, OLA-NO2 modestly but significantly reduces macrophage oxidative status and cellular triglyceride content via modulation of cellular anti-oxidants and triglyceride

  16. Radix Astragali Improves Dysregulated Triglyceride Metabolism and Attenuates Macrophage Infiltration in Adipose Tissue in High-Fat Diet-Induced Obese Male Rats through Activating mTORC1-PPARγ Signaling Pathway

    Yang Long

    2014-01-01

    Full Text Available Increased levels of free fatty acids (FFAs and hypertriglyceridemia are important risk factors for cardiovascular disease. The effective fraction isolated from radix astragali (RA has been reported to alleviate hypertriglyceridemia. The mechanism of this triglyceride-lowering effect of RA is unclear. Here, we tested whether activation of the mTORC1-PPARγ signaling pathway is related to the triglyceride-lowering effect of RA. High-fat diet-induced obese (DIO rats were fed a high-fat diet (40% calories from fat for 9-10 weeks, and 4 g/kg/d RA was administered by gavage. RA treatment resulted in decreased fasting triglyceride levels, FFA concentrations, and adipocyte size. RA treated rats showed improved triglyceride clearance and fatty acid handling after olive oil overload. RA administration could also decrease macrophage infiltration and expression of MCP-1 and TNFα, but it may also increase the expression of PPARγ in epididymal adipose tissue from RA treated rats. Consistently, expressions of PPARγ and phospho-p70S6K were increased in differentiated 3T3-L1 adipocytes treated with RA. Moreover, RA couldnot upregulate the expression of PPARγ at the presence of rapamycin. In conclusion, the mTORC1-PPARγ signaling pathway is a potential mechanism through which RA exerts beneficial effects on the disturbance of triglyceride metabolism and dysfunction of adipose tissue in DIO rats.

  17. PPARγ activation alters fatty acid composition in adipose triglyceride, in addition to proliferation of small adipocytes, in insulin resistant high-fat fed rats.

    Sato, Daisuke; Oda, Kanako; Kusunoki, Masataka; Nishina, Atsuyoshi; Takahashi, Kazuaki; Feng, Zhonggang; Tsutsumi, Kazuhiko; Nakamura, Takao

    2016-02-15

    It was reported that adipocyte size is potentially correlated in part to amount of long chain polyunsaturated fatty acids (PUFAs) and insulin resistance because several long chain PUFAs can be ligands of peroxisome proliferator-activated receptors (PPARs). In our previous study, marked reduction of PUFAs was observed in insulin-resistant high-fat fed rats, which may indicate that PUFAs are consumed to improve insulin resistance. Although PPARγ agonist, well known as an insulin sensitizer, proliferates small adipocytes, the effects of PPARγ agonist on FA composition in adipose tissue have not been clarified yet. In the present study, we administered pioglitazone, a PPARγ agonist, to high-fat fed rats, and measured their FA composition of triglyceride fraction in adipose tissue and adipocyte diameters in pioglitazone-treated (PIO) and non-treated (control) rats. Insulin sensitivity was obtained with hyperinsulinemic euglycemic clamp. Average adipocyte diameter in the PIO group were smaller than that in the control one without change in tissue weight. In monounsaturated FAs (MUFAs), 14:1n-5, 16:1n-7, and 18:1n-9 contents in the PIO group were lower than those, respectively, in the control group. In contrast, 22:6n-3, 20:3n-6, 20:4n-6, and 22:4n-6 contents in the PIO group were higher than those, respectively, in the control group. Insulin sensitivity was higher in the PIO group than in the control one. These findings suggest that PPARγ activation lowered MUFAs whereas suppressed most of C20 or C22 PUFAs reduction, and that the change of fatty acid composition may be relevant with increase in small adipocytes. PMID:26825545

  18. Relationship of adiposity to the population distribution of plasma triglyceride concentrations in vigorously active men and women

    Williams, Paul T.

    2002-12-21

    Context and Objective: Vigorous exercise, alcohol and weight loss are all known to increase HDL-cholesterol, however, it is not known whether these interventions raise low HDL as effectively as has been demonstrated for normal HDL. Design: Physician-supplied medical data from 7,288 male and 2,359 female runners were divided into five strata according to their self-reported usual running distance, reported alcohol intake, body mass index (BMI) or waist circumference. Within each stratum, the 5th, 10th, 25th, 50th, 75th, 90th, and 95th percentiles for HDL-cholesterol were then determined. Bootstrap resampling of least-squares regression was applied to determine the cross-sectional relationships between these factors and each percentile of the HDL-cholesterol distribution. Results: In both sexes, the rise in HDL-cholesterol per unit of vigorous exercise or alcohol intake was at least twice as great at the 95th percentile as at the 5th percentile of the HDL-distribution. There was also a significant graded increase in the slopes relating exercise (km run) and alcohol intake to HDL between the 5th and the 95th percentile. Men's HDL-cholesterol decreased in association with fatness (BMI and waist circumference) more sharply at the 95th than at the 5th percentile of the HDL-distribution. Conclusions: Although exercise, alcohol and adiposity were all related to HDL-cholesterol, the elevation in HDL per km run or ounce of alcohol consumed, and reduction in HDL per kg of body weight (men only), was least when HDL was low and greatest when HDL was high. These cross-sectional relationships support the hypothesis that men and women who have low HDL-cholesterol will be less responsive to exercise and alcohol (and weight loss in men) as compared to those who have high HDL-cholesterol.

  19. The effect of a single lethal X-irradiation exposure on the activity of lipoprotein lipase in the tissues of the rat

    Wistar male rats, both fed and fasting for 16 h prior to irradiation, were exposed to a single lethal X-ray dose of 387 mC/kg (1500R). The activity of lipoprotein lipase in white adipose (epididymal) tissue and heart muscle and the concentration of serum triglycerides were determined at 1, 6, 24, 48, and 72 h after irradiation. In the early time periods, at 1 and 6 h after exposure, the activity of lipoprotein lipase decreased in adipose tissue and increased in heart muscle of the irradiated fed rats; in fasting rats it decreased in heart muscle at 1 h after exposure. The concentration of serum triglycerides increased at 1 h and decreased at 6 h after exposure in fed rats. In these rats, alterations in serum triglycerides correlated with changes in lipoprotein lipase activity in adipose tissue. Alterations observed at the later time periods were more dependent on the time interval between irradiation and the analysis. Lipoprotein lipase activity increased with time after irradiation up to the maximal values at 72 h. Fasting prior to and after irradiation substantially modified the response of animals to radiation. (author)

  20. High-throughput virtual screening with e-pharmacophore and molecular simulations study in the designing of pancreatic lipase inhibitors

    Veeramachaneni GK; Raj KK; Chalasani LM; JS, Bondili; Talluri VR

    2015-01-01

    Ganesh Kumar Veeramachaneni, K Kranthi Raj, Leela Madhuri Chalasani, Jayakumar Singh Bondili, Venkateswara Rao Talluri Department of Biotechnology, K L University, Guntur, India Background: Obesity is a progressive metabolic disorder in the current world population, and is characterized by the excess deposition of fat in the adipose tissue. Pancreatic lipase is one of the key enzymes in the hydrolysis of triglycerides into monoglycerides and free fatty acids, and is thus considered a promis...

  1. Increased Oxidative Stress Impairs Adipose Tissue Function in Sphingomyelin Synthase 1 Null Mice

    Masato Yano; Tadashi Yamamoto; Naotaka Nishimura; Tomomi Gotoh; Ken Watanabe; Kazutaka Ikeda; Yohei Garan; Ryo Taguchi; Koichi Node; Toshiro Okazaki; Yuichi Oike

    2013-01-01

    Sphingomyelin synthase 1 (SMS1) catalyzes the conversion of ceramide to sphingomyelin. Here, we found that SMS1 null mice showed lipodystrophic phenotype. Mutant mice showed up-regulation of plasma triglyceride concentrations accompanied by reduction of white adipose tissue (WAT) as they aged. Lipoprotein lipase (LPL) activity was severely reduced in mutant mice. In vivo analysis indicated that fatty acid uptake in WAT but not in liver decreased in SMS1 null compared to wild-type mice. In vit...

  2. Characterization of lipase activities in obese Pima indians. Decreases with weight reduction.

    Reitman, J S; Kosmakos, F C; Howard, B V; Taskinen, M R; Kuusi, T.; Nikkila, E A

    1982-01-01

    Adipose tissue and muscle lipoprotein lipase and postheparin hepatic and lipoprotein lipase activities have been measured in a group of 21 Pima Indian males over a wide range of body weight to determine the relationship between obesity and these lipase activities. There was a significant positive correlation between adipose tissue lipoprotein lipase and obesity; muscle and postheparin lipoprotein lipase and hepatic lipase were not related to degree of obesity. Fasting insulin levels were not ...

  3. Phospholipase C-related catalytically inactive protein (PRIP regulates lipolysis in adipose tissue by modulating the phosphorylation of hormone-sensitive lipase.

    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.

  4. Effects of 2 G on adiposity, leptin, lipoprotein lipase, and uncoupling protein-1 in lean and obese Zucker rats

    Warren, L. E.; Horwitz, B. A.; Hamilton, J. S.; Fuller, C. A.

    2001-01-01

    Male Zucker rats were exposed to 2 G for 8 wk to test the hypothesis that the leptin regulatory pathway contributes to recovery from effects of 2 G on feeding, growth, and nutrient partitioning. After initial hypophagia, body mass-independent food intake of the lean rats exposed to 2 G surpassed that of the lean rats maintained at 1 G, but food intake of the obese rats exposed to 2 G remained low. After 8 wk at 2 G, body mass and carcass fat were less in both genotypes. Leptin and percent fat were lower in lean rats exposed to 2 G vs. 1 G but did not differ in obese rats exposed to 2 G vs. 1 G. Although exposure to 2 G did not alter uncoupling protein-1 levels, it did elicit white fat pad-specific changes in lipoprotein lipase activity in obese but not lean rats. We conclude that 2 G affects both genotypes but that the lean Zucker rats recover their food intake and growth rate and retain "normal" lipoprotein lipase activity to a greater degree than do the obese rats, emphasizing the importance of a functional leptin regulatory pathway in this acclimation.

  5. Triglyceride level

    ... page: //medlineplus.gov/ency/article/003493.htm Triglyceride level To use the sharing features on this page, ... and Metabolism; Council on Arteriosclerosis, Thrombosis and Vascular Biology; Council on Cardiovascular Nursing; Council on the Kidney ...

  6. Triglycerides Test

    ... Cholesterol ; LDL Cholesterol ; Direct LDL Cholesterol ; VLDL Cholesterol ; Lipid Profile ; Cardiac Risk Assessment All content on Lab Tests ... tests for triglycerides are usually part of a lipid profile used to identify the risk of developing heart ...

  7. Silicon dioxide nanoparticles increase macrophage atherogenicity: Stimulation of cellular cytotoxicity, oxidative stress, and triglycerides accumulation.

    Petrick, Lauren; Rosenblat, Mira; Paland, Nicole; Aviram, Michael

    2016-06-01

    Nanoparticle research has focused on their toxicity in general, while increasing evidence points to additional specific adverse effects on atherosclerosis development. Arterial macrophage cholesterol and triglyceride (TG) accumulation and foam cell formation are the hallmark of early atherogenesis, leading to cardiovascular events. To investigate the in vitro atherogenic effects of silicon dioxide (SiO2 ), J774.1 cultured macrophages (murine cell line) were incubated with SiO2 nanoparticle (SP, d = 12 nm, 0-20 µg/mL), followed by cellular cytotoxicity, oxidative stress, TG and cholesterol metabolism analyses. A significant dose-dependent increase in oxidative stress (up to 164%), in cytotoxicity (up to 390% measured by lactate dehydrogenase (LDH) release), and in TG content (up to 63%) was observed in SiO2 exposed macrophages compared with control cells. A smaller increase in macrophage cholesterol mass (up to 22%) was noted. TG accumulation in macrophages was not due to a decrease in TG cell secretion or to an increased TG biosynthesis rate, but was the result of attenuated TG hydrolysis secondary to decreased lipase activity and both adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) protein expression (by 42 and 25%, respectively). Overall, SPs showed pro-atherogenic effects on macrophages as observed by cytotoxicity, increased oxidative stress and TG accumulation. © 2014 Wiley Periodicals, Inc. Environ Toxicol 31: 713-723, 2016. PMID:25448404

  8. Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia.

    Tsoli, Maria; Swarbrick, Michael M; Robertson, Graham R

    2016-06-01

    Although muscle wasting is the obvious manifestation of cancer cachexia that impacts on patient quality of life, the loss of lipid reserves and metabolic imbalance in adipose tissue also contribute to the devastating impact of cachexia. Depletion of fat depots in cancer patients is more pronounced than loss of muscle and often precedes, or even occurs in the absence of, reduced lean body mass. Rapid mobilisation of triglycerides stored within adipocytes to supply the body with fatty acids in periods of high-energy demand is normally mediated through a well-defined process of lipolysis involving the lipases ATGL, HSL and MGL. Studies into how these lipases contribute to fat loss in cancer cachexia have revealed the prominent role for ATGL in initiating lipolysis during adipose tissue atrophy, together with links between tumour-derived factors and the signalling pathways that control lipid flux within fat cells. The recent findings of increased thermogenesis in brown fat during cancer cachexia indicate that metabolically active adipose tissue contributes to the imbalance in energy homeostasis involved in catabolic wasting. Such energetically futile use of fatty acids liberated from adipose tissue to generate heat represents a maladaptive response in conjunction with anorexia experienced by cancer patients. As IL-6 release by tumours provokes lipolysis and activates the thermogenic programme in brown fat, this review explores the overlap in dysregulated metabolic processes due to inflammatory mediators in cancer cachexia and other disease states characterised by elevated cytokines such as obesity and diabetes. PMID:26529279

  9. Overview of fungal lipase: a review.

    Singh, Abhishek Kumar; Mukhopadhyay, Mausumi

    2012-01-01

    Lipases (triacylglycerolacyl hydrolases, EC3.1.1.3) are class of enzymes which catalyze the hydrolysis of long-chain triglycerides. In this review paper, an overview regarding the fungal lipase production, purification, and application is discussed. The review describes various industrial applications of lipase in pulp and paper, food, detergent, and textile industries. Some important lipase-producing fungal genera include Aspergillus, Penicillium, Rhizopus, Candida, etc. Current fermentation process techniques such as batch, fed-batch, and continuous mode of lipase production in submerged and solid-state fermentations are discussed in details. The purification of lipase by hydrophobic interaction chromatography is also discussed. The development of mathematical models applied to lipase production is discussed with special emphasis on lipase engineering. PMID:22072143

  10. 脂肪细胞三酰甘油分解代谢相关调节的研究进展%Research progress in regulation of triglyceride hydrolysis in adipocytes

    黄文钰

    2013-01-01

    Adipose tissue is an important station for energy storage and service in the body.The dysregulation of triglyceride hydrolysis is related to obesity and other lipid metabolism disorders.Hormone-sensitive lipase (HSL) and adipose triacylglycerol lipase(ATGL) are major enzymes for triglyceride hydrolysis.Perilipin is an important regulatory factor for lipolysis.This review summarized advance in research on the main regulatory pathway for triglyceride hydrolysis and the roles of HSL,ATGL,and perilipin in triglyceride hydrolysis in adipocytes.%脂肪组织是体内重要的能量储存和供应站,脂肪细胞中的三酰甘油分解代谢紊乱与肥胖等代谢疾病密切相关.在多种脂肪分解途径中,有许多机制尚未明确.已知激素敏感性脂肪酶、脂肪三酰甘油脂肪酶是重要的脂肪细胞三酰甘油水解酶,围脂滴蛋白是脂肪分解的重要调节因子.本综述将着重介绍脂肪细胞三酰甘油分解代谢的主要调节通路和上述酶及蛋白作用机制方面的研究进展.

  11. Leu452His mutation in lipoprotein lipase gene transfer associated with hypertriglyceridemia in mice in vivo.

    Kaiyue Sun

    Full Text Available Mutated mouse lipoprotein lipase (LPL containing a leucine (L to histidine (H substitution at position 452 was transferred into mouse liver by hydrodynamics-based gene delivery (HD. Mutated-LPL (MLPL gene transfer significantly increased the concentrations of plasma MLPL and triglyceride (TG but significantly decreased the activity of plasma LPL. Moreover, the gene transfer caused adiposis hepatica and significantly increased TG content in mouse liver. To understand the effects of MLPL gene transfer on energy metabolism, we investigated the expression of key functional genes related to energy metabolism in the liver, epididymal fat, and leg muscles. The mRNA contents of hormone-sensitive lipase (HSL, adipose triglyceride lipase (ATGL, fatty acid-binding protein (FABP, and uncoupling protein (UCP were found to be significantly reduced. Furthermore, we investigated the mechanism by which MLPL gene transfer affected fat deposition in the liver, fat tissue, and muscle. The gene expression and protein levels of forkhead Box O3 (FOXO3, AMP-activated protein kinase (AMPK, and peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC-1α were found to be remarkably decreased in the liver, fat and muscle. These results suggest that the Leu452His mutation caused LPL dysfunction and gene transfer of MLPL in vivo produced resistance to the AMPK/PGC-1α signaling pathway in mice.

  12. Pancreatic Lipase-related Protein 2 Is the Major Colipase-Dependent Pancreatic Lipase in Suckling Mice1

    D’Agostino, Dymphna; Lowe, Mark E.

    2004-01-01

    Suckling mice express colipase before the expression of pancreatic triglyceride lipase. Yet, efficient fat digestion in newborns requires colipase, suggesting that colipase may act as a cofactor for another lipase such as pancreatic lipase-related protein 2 (PLRP2). We determined whether PLRP2 or another lipase depends on colipase for maximal activity in newborn mice by analyzing extracts from the pancreas of 4-d-old colipase-deficient and PLRP2-deficient mice. Pancreatic extracts from colipa...

  13. Lipase Test

    ... be limited. Home Visit Global Sites Search Help? Lipase Share this page: Was this page helpful? Also known as: LPS Formal name: Lipase Related tests: Amylase , Trypsin , Trypsinogen At a Glance ...

  14. Effect of extended-release niacin on hormone-sensitive lipase and lipoprotein lipase in patients with HIV-associated lipodystrophy syndrome

    Dominic C Chow

    2008-11-01

    Full Text Available Dominic C Chow, Anne Tasaki, Jill Ono, Bruce Shiramizu, Scott A SouzaHawaii AIDS Clinical Research Program, University of Hawaii, Honolulu, HI, USABackground: HIV-associated lipodystrophy syndrome is strongly associated with antiretroviral treatment in patients with human immunodeficiency virus (HIV. Niacin is thought to affect hormone-sensitive lipase (HSL and lipoprotein lipase (LPL expression in peripheral and intra-abdominal fat (IAF.Objective: This study investigated the effect of extended-release niacin (ERN on adipose HSL and LPL expression in patients with HIV-associated lipodystrophy syndrome.Methods: Changes in IAF and peripheral fat content and HSL and LPL expression were examined in 4 HIV-infected patients recruited from a prospective study treated with ERN. Patients underwent limited 8 slice computerized tomography abdominal scans, dual-energy X-ray absorptiometry scans, and skin punch biopsies of the mid-thigh at baseline and after 12 weeks of ERN. All subjects were on stable highly active antiretroviral therapy prior to and during the study. Changes in body habitus were self-reported.Results: Normalized HSL expression decreased in 3 patients and normalized LPL expression increased in all 4 patients when comparing pre- and post-ERN treated samples. All subjects showed a decrease in total cholesterol (TC and triglyceride (TG levels.Conclusions: Preliminary analysis suggests ERN may induce changes in HSL and LPL expression. This method is a feasible approach to identify changes in adipose RNA expression involved with lipolysis.Keywords: extended-release niacin, HIV, lipodystrophy syndrome, hormone-sensitive lipase (HSL, lipoprotein lipase (LPL

  15. Adipocyte triglyceride turnover and lipolysis in lean and overweight subjects.

    Ryden, M; Andersson, D. P.; Bernard, S.; Spalding, K.; Arner, P

    2013-01-01

    Human obesity is associated with decreased triglyceride turnover and impaired lipolysis in adipocytes. We determined whether such defects also occur in subjects with only moderate increase in fat mass. Human abdominal subcutaneous adipose tissue was investigated in healthy, nonobese subjects [body mass index (BMI) > 17 kg/m2 and BMI < 30 kg/m2]. Triglyceride age, reflecting lipid turnover, was examined in 41 subjects by assessing the incorporation of atmospheric 14C into adipose lipids. Adipo...

  16. New finding and optimal production of a novel extracellular alkaline lipase from Yarrowia lipolytica NRRL Y-2178

    Lipases are industrially and useful versatile enzymes that catalyze numerous different reactions including hydrolysis of triglycerides, transesterification, and chiral synthesis of esters under natural conditions. Although lipases from various sources have been widely used in industrial application...

  17. Hydrolysis of human milk fat globules by pancreatic lipase: role of colipase, phospholipase A2, and bile salts.

    Bläckberg, L; Hernell, O; Olivecrona, T

    1981-01-01

    Human milk fat globules were used to explore how dietary triglycerides are hydrolyzed by pancreatic lipase. These triglycerides were hydrolyzed very slowly by lipase alone as if the surface layer of proteins and phospholipids impeded the action of the enzyme. The inhibition of lipase activity could be overcome by addition either of colipase or of pancreatic phospholipase A2. Colipase enhanced triglyceride hydrolysis in a dose-dependent manner whether bile salts were present or not. Bile salts...

  18. Regulation of G0/G1 switch gene 2 (G0S2) expression in human adipose tissue.

    Skopp, Alexander; May, Marcus; Janke, Juergen; Kielstein, Heike; Wunder, Ruth; Flade-Kuthe, Ricarda; Kuthe, Andreas; Jordan, Jens; Engeli, Stefan

    2016-05-01

    The G0/G1 switch gene 2 (G0S2) protein attenuated adipose triglyceride lipase (ATGL) activity and decreased lipolysis in rodent and human adipocytes. We hypothesized that G0S2 mRNA expression in human adipose tissue is influenced by depot, adipocyte size, body weight and caloric intake. Adipose tissue samples were obtained during abdominal surgery and by needle biopsy before and 3 h after an extended glucose load in lean subjects. G0S2 mRNA was 7× higher expressed in mature human adipocytes compared to the stromavascular fraction. Cell size inversely correlated with G0S2 mRNA expression in both, subcutaneous and omental adipose depots. G0S2 mRNA expression was 75% higher in subcutaneous compared to omental adipose tissue. Obesity was associated with lower G0S2 mRNA expression in subcutaneous adipose tissue. Acute glucose ingestion after an overnight fast did not significantly increase G0S2 expression in subcutaneous adipose tissue. In conclusion, differences in G0S2 expression may explain depot-specific and obesity-associated differences in lipolysis on the molecular level. PMID:26707160

  19. Pancreatic lipase-related protein 2 digests fats in human milk and formula in concert with gastric lipase and carboxyl ester lipase

    Johnson, Karin; Ross, Leah; Miller, Rita; Xiao, Xunjun; Lowe, Mark E.

    2013-01-01

    INTRODUCTION Dietary fats must be digested into fatty acids and monoacylglycerols prior to absorption. In adults, colipase-dependent pancreatic triglyceride lipase (PTL) contributes significantly to fat digestion. In newborn rodents and humans, the pancreas expresses low levels of PTL. In rodents, a homologue of PTL, pancreatic lipase related protein 2 (PLRP2) and carboxyl ester lipase (CEL) compensate for the lack of PTL. In human newborns, the role for PLRP2 in dietary fat digestion is uncl...

  20. Lipase Induction in Mucor hiemalis

    Akhtar, M. Waheed; Mirza, A. Q.; Chughtai, M. I. D.

    1980-01-01

    The influence on lipase induction in Mucor hiemalis of different types of triglycerides containing mainly oleic acid (olive oil), erucic acid (mustard oil), or saturated fatty acids of 8 to 16 carbons (coconut oil) was studied. The fungus was grown in shake flasks in a fermentation medium containing peptone, minerals, and glucose or one of the oils as the carbon source. Maximum lipase was produced when the initial pH of the fermentation medium was kept at 4.0. Addition of Ca2+ to the medium d...

  1. Exercise-induced lactate accumulation regulates intramuscular triglyceride metabolism via transforming growth factor-β1 mediated pathways.

    Nikooie, Rohollah; Samaneh, Sajadian

    2016-01-01

    The mechanism regulating the utilization of intramuscular triacylglycerol (IMTG) during high-intensity interval training (HIIT) and post-exercise recovery period remains elusive. In this study, the acute and long-term effects of HIIT on transforming growth factor beta 1 (TGF-β1) abundance in rat skeletal muscle and role of lactate and TGF-β1 in IMTG lipolysis during post-exercise recovery period were examined. TGF-β1 and Adipose triacylglycerol lipase (ATGL) abundance as well as total lipase activity in the gastrocnemius muscle significantly increased to a maximum value 10 h after acute bout of HIIT. Inhibition of TGF-β1 signaling by intramuscular injection of SB431542 30 min prior to the acute exercise attenuated ATGL abundance and total lipase activity in the gastrocnemius muscle in response to acute exercise. Intramuscular acute injection of lactate increased TGF-β1 and ATGL abundance in the gastrocnemius muscle and there were a significant increase in Muscle TGF-β1 and ATGL abundance after 5 weeks of HIIT/lactate treatment. These results indicate that exercise-induced lactate accumulation regulates intramuscular triglyceride metabolism via transforming growth factor-β1 mediated pathways during post-exercise recovery from strenuous exercise. PMID:26522131

  2. Regulation of G0/G1 Switch Gene 2 (G0S2) Protein Ubiquitination and Stability by Triglyceride Accumulation and ATGL Interaction

    Heckmann, Bradlee L.; Zhang, Xiaodong; Saarinen, Alicia M.; Liu, Jun

    2016-01-01

    Intracellular triglyceride (TG) hydrolysis or lipolysis is catalyzed by the key intracellular triglyceride hydrolase, adipose triglyceride lipase (ATGL). The G0/G1 Switch Gene 2 (G0S2) was recently identified as the major selective inhibitor of ATGL and its hydrolase function. Since G0S2 levels are dynamically linked and rapidly responsive to nutrient status or metabolic requirements, the identification of its regulation at the protein level is of significant value. Earlier evidence from our laboratory demonstrated that G0S2 is a short-lived protein degraded through the proteasomal pathway. However, little is currently known regarding the underlying mechanisms. In the current study we find that 1) protein degradation is initiated by K48-linked polyubiquitination of the lysine- 25 in G0S2; and 2) G0S2 protein is stabilized in response to ATGL expression and TG accumulation. Mutation of lysine-25 of G0S2 abolished ubiquitination and increased protein stability. More importantly, G0S2 was stabilized via different mechanisms in the presence of ATGL vs. in response to fatty acid (FA)-induced TG accumulation. Furthermore, G0S2 protein but not mRNA levels were reduced in the adipose tissue of ATGL-deficient mice, corroborating the involvement of ATGL in the stabilization of G0S2. Taken together our data illustrate for the first time a crucial multifaceted mechanism for the stabilization of G0S2 at the protein level. PMID:27248498

  3. Lipases in Medicine: An Overview.

    Loli, Heni; Narwal, Sunil Kumar; Saun, Nitin Kumar; Gupta, Reena

    2015-01-01

    Lipases are part of the family of hydrolases that act on carboxylic ester bonds. They are involved in catalyzing the hydrolysis of triglycerides (TG) into chylomicrons and very low density lipoprotein (VLDL) particles. Uses of lipases are evolving rapidly and currently they are reported to show high potential in medicine. Intensive study and investigations have led researchers to explore lipases for their use in substitution therapy, where in enzyme deficiency during diseased conditions is compensated by their external administration. In our body, they are used to break down fats present in food so that they can be absorbed in the intestine and deficiency of lipases leads to malabsorption of fats and fat-soluble vitamins. Lipases help a person who has cystic fibrosis, Alzheimer's disease, atherosclerosis and act as a candidate target for cancer prevention and therapy. They act as diagnostic tool and their presence or increasing levels can indicate certain infection or disease. Obesity causes metabolic disease and is a serious health problem around the world. Thus inhibiting digestive lipase to reduce fat absorption has become the main pharmacological approach to the treatment of obesity in recent years. PMID:26156413

  4. Bacterial lipases

    Jaeger, Karl-Erich; Ransac, Stéphane; Dijkstra, Bauke W.; Colson, Charles; Heuvel, Margreet van; Misset, Onno

    1994-01-01

    Many different bacterial species produce lipases which hydrolyze esters of glycerol with preferably long-chain fatty acids. They act at the interface generated by a hydrophobic lipid substrate in a hydrophilic aqueous medium. A characteristic property of lipases is called interfacial activation, mea

  5. Serum pancreatic lipase as a screening test for cystic fibrosis.

    Adriaenssens, K; Van Riel, L

    1982-01-01

    Pancreatic lipase catalyses the hydrolysis of emulsified triglycerides to form a transparent solution of monoglycerides and fatty acids. Levels of serum pancreatic lipase were measured in neonates known to have cystic fibrosis and compared with levels in control infants. During the first weeks of life infants with cystic fibrosis had raised serum pancreatic lipase values in parallel with raised serum trypsin values. A simple and specific turbidimetric dried blood spot assay for serum pancreat...

  6. Tofogliflozin Improves Insulin Resistance in Skeletal Muscle and Accelerates Lipolysis in Adipose Tissue in Male Mice.

    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. PMID:26713783

  7. I. Lipid metabolism stimulated by altered intracellular calcium in cultured fibroblasts. II. Regulation of the activity of rat adipose tissue lipoprotein lipase

    The cell killing process of 3T3 Swiss mouse fibroblasts stimulated by Ca2+ plus A23187, a Ca2+ ionophore has been studied. The aim of this research is to understand the biochemical mechanism of this process, i.e, to elucidate the step involved and to characterize the enzymes involved with each steps in the lipid metabolism stimulated in cultured fibroblasts undergoing a toxic death response. Parallel 3T3 cultures biosynthetically labeled with lipid precursors were examined under Ca2+-mediated killing conditions. Labeled lipids were extracted and analyzed by thin-layer chromatography and autoradiography. Evidence for activation of a phosphatidylinositol-specific phospholipase C has been obtained in injured 3T3 cells labeled with [3H]glycerol and [3H]inositol. To simplify the system for studying the lipoprotein lipase reaction, our laboratory prepared the chromophore containing a substrate: 1,2-dipalmitoyl-3-β-2-furylacryloyltriacylglycerol (DPFATG). By using this artificial lipid we could readily investigate the lipoprotein lipase reactions, since the absorbance change directly represents the hydrolysis of the chromophoric side chain of the substrate

  8. Production of biodiesel by transesterification of corn and soybean oils with ethanol or butanol using resin-bound truncated Candida antarctica lipase B

    Enzymatic catalysts, such as lipases, have advantages over chemical catalysts for transesterification of triglycerides to produce biodiesel. A gene encoding a synthetic truncated Candida antarctica lipase B (CALB) was generated via automated PCR and expressed in Saccharomyces cerevisiae. Western b...

  9. Lipase test

    ... the bowel (bowel obstruction) Celiac disease Duodenal ulcer Cancer of the pancreas Infection or swelling of the pancreas This test may also be done for familial lipoprotein lipase deficiency . Risks ... Update Date 2/4/2015 Updated ...

  10. Diagnostic value of post-heparin lipase testing in detecting common genetic variants in the LPL and LIPC genes

    van Hoek, Mandy; Dallinga-Thie, Geesje M.; Ewout W Steyerberg; Sijbrands, Eric J. G.

    2009-01-01

    Post-heparin lipoprotein lipase and hepatic lipase activities are used to identify primary disorders of triglyceride and HDL-cholesterol metabolism. Their ability to identify common variants in the lipoprotein lipase (LPL) and hepatic lipase (LIPC) genes is unclear. To investigate the ability of lipase testing to detect common lipase gene variants, we included 183 patients who had undergone post-heparin lipase testing and genotyped the LPL D9N, N291S, PvuII, HindIII, and S447X and the LIPC-51...

  11. Effect of medium chain triglycerides on brown adipose tissue in C57BL/6J mice%中链甘油三酯对C57BL/6J小鼠棕色脂肪组织的影响

    张永; 刘英华; 张新胜; 于晓明; 徐庆; 王觐; 宫雪; 杨雪艳; 薛长勇

    2011-01-01

    Objective To study the effect of medium chain triglycerides(MCT) on brown adipose tissue(BAT) in C57BL/6J mice. Methods Thirty male C57BL/6J mice at the age 4-5 weeks, enrolled in this study, were randomly divided into MCT group, LCT group and control group( 10 in each group). Animals in the first two groups were fed with high fat diet containing MCT or LCT, and those in control group were fed with standard chow for 15 weeks. Body weight, subscapular brown fat mass, diet consumption, and uncoupled protein-1(UCP1) expression in BAT of different groups were observed. Results After 15 weeks, the body weight and body fat mass were significantly lower in MCT group than in LCT group(P0.05). The brown fat mass and UCP1 expression were significantly higher in MCT group than in LCT group(P<0.05). Conclusion MCT can inhibit the increase of body mass and accumulation of body fat due to high fat diet by increasing brown fat mass, UCP1 expression and heat production in brown fat tissue.%目的 观察中链甘油三酯(MCT)对C57BL/6J小鼠棕色脂肪组织的影响.方法 选择4-5周龄C57BL/6J雄性小鼠30只,随机分为中链甘油三酯高脂组(MCT),大豆油高脂组(LCT)及普通饲料对照组,每组10只,喂饲15周.观察研究前后各组间小鼠体质量、饲料消耗量及食物功效比、棕色脂肪组织重量差异以及解偶联蛋白-1(UCP1)表达水平的变化.结果 研究结束时,MCT高脂组小鼠的体质量、体脂肪量显著低于LCT组(P<0.05),饲料消耗量MCT组和LCT组之间无统计学差异(P>0.05),MCT组棕色脂肪组织重量及UCP1蛋白表达量显著高于LCT组.结论 MCT可促进棕色脂肪组织增殖,提高棕色脂肪组织UCP1的表达,增强棕色脂肪组织的产热功能,从而抑制高脂饲料诱发的C57BL/6J小鼠体质量增加和体脂肪积累.

  12. Triglycerides and cardiovascular disease

    Nordestgaard, Børge G; Varbo, Anette

    2014-01-01

    cholesterol might not cause cardiovascular disease as originally thought has now generated renewed interest in raised concentrations of triglycerides. This renewed interest has also been driven by epidemiological and genetic evidence supporting raised triglycerides, remnant cholesterol, or triglyceride......-rich lipoproteins as an additional cause of cardiovascular disease and all-cause mortality. Triglycerides can be measured in the non-fasting or fasting states, with concentrations of 2-10 mmol/L conferring increased risk of cardiovascular disease, and concentrations greater than 10 mmol/L conferring increased risk...... of acute pancreatitis and possibly cardiovascular disease. Although randomised trials showing cardiovascular benefit of triglyceride reduction are scarce, new triglyceride-lowering drugs are being developed, and large-scale trials have been initiated that will hopefully provide conclusive evidence...

  13. PLTP activity in premenopausal women. Relationship with lipoprotein lipase, HDL, LDL, body fat, and insulin resistance.

    Murdoch, S J; Carr, M C; Hokanson, J E; Brunzell, J D; Albers, J J

    2000-02-01

    Plasma phospholipid transfer protein (PLTP) is thought to play a major role in the facilitated transfer of phospholipids between lipoproteins and in the modulation of high density lipoprotein (HDL) particle size and composition. However, little has been reported concerning the relationships of PLTP with plasma lipoprotein parameters, lipolytic enzymes, body fat distribution, insulin, and glucose in normolipidemic individuals, particularly females. In the present study, 50 normolipidemic healthy premenopausal females were investigated. The relationships between the plasma PLTP activity and selected variables were assessed. PLTP activity was significantly and positively correlated with low density lipoprotein (LDL) cholesterol (r(s) = 0.53), apoB (r(s) = 0.44), glucose (r(s) = 0.40), HDL cholesterol (r(s) = 0.38), HDL(3) cholesterol (r(s) = 0.37), lipoprotein lipase activity (r(s) = 0.36), insulin (r(s) = 0.33), subcutaneous abdominal fat (r(s) = 0.36), intra-abdominal fat (r(s) = 0.29), and body mass index (r(s) = 0.29). HDL(2) cholesterol, triglyceride, and hepatic lipase were not significantly related to PLTP activity. As HDL(2) can be decreased by hepatic lipase and hepatic lipase is increased in obesity with increasing intra-abdominal fat, the participants were divided into sub-groups of non-obese (n = 35) and obese (n = 15) individuals and the correlation of PLTP with HDL(2) cholesterol was re-examined. In the non-obese subjects, HDL(2) cholesterol was found to be significantly and positively related to PLTP activity (r(s) = 0.44). Adjustment of the HDL(2) values for the effect of hepatic lipase activity resulted in a significant positive correlation between PLTP and HDL(2) (r(s) = 0.41), indicating that the strength of the relationship between PLTP activity and HDL(2) can be reduced by the opposing effect of hepatic lipase on HDL(2) concentrations. We conclude that PLTP-facilitated lipid transfer activity is related to HDL and LDL metabolism, as well as

  14. GPIHBP1 and Plasma Triglyceride Metabolism

    Fong, Loren G; Young, Stephen G; Beigneux, Anne P;

    2016-01-01

    GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries...... - such that lipolytic processing can proceed. GPIHBP1 also reduces the unfolding of the LPL catalytic domain, thereby stabilizing LPL catalytic activity. Many different GPIHBP1 mutations have been identified in patients with severe hypertriglyceridemia (chylomicronemia), the majority of which interfere...... with folding of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research....

  15. GPIHBP1 and Plasma Triglyceride Metabolism.

    Fong, Loren G; Young, Stephen G; Beigneux, Anne P; Bensadoun, André; Oberer, Monika; Jiang, Haibo; Ploug, Michael

    2016-07-01

    GPIHBP1, a GPI-anchored protein in capillary endothelial cells, is crucial for the lipolytic processing of triglyceride-rich lipoproteins (TRLs). GPIHBP1 shuttles lipoprotein lipase (LPL) to its site of action in the capillary lumen and is essential for the margination of TRLs along capillaries - such that lipolytic processing can proceed. GPIHBP1 also reduces the unfolding of the LPL catalytic domain, thereby stabilizing LPL catalytic activity. Many different GPIHBP1 mutations have been identified in patients with severe hypertriglyceridemia (chylomicronemia), the majority of which interfere with folding of the protein and abolish its capacity to bind and transport LPL. The discovery of GPIHBP1 has substantially revised our understanding of intravascular triglyceride metabolism but has also raised many new questions for future research. PMID:27185325

  16. Acid Lipase Disease

    ... Enhancing Diversity Find People About NINDS NINDS Acid Lipase Disease Information Page Synonym(s): Cholesterol Ester Storage Disease, ... Related NINDS Publications and Information What is Acid Lipase Disease ? Acid lipase disease or deficiency occurs when ...

  17. Mechanisms of lipase maturation

    Doolittle, Mark H.; Péterfy, Miklós

    2010-01-01

    Lipases are acyl hydrolases that represent a diverse group of enzymes present in organisms ranging from prokaryotes to humans. This article focuses on an evolutionarily related family of extracellular lipases that include lipoprotein lipase, hepatic lipase and endothelial lipase. As newly synthesized proteins, these lipases undergo a series of co- and post-translational maturation steps occurring in the endoplasmic reticulum, including glycosylation and glycan processing, and protein folding ...

  18. Isolation and characterization of some moderately halophilic bacteria with lipase activity.

    Ghasemi, Y; Rasoul-Amini, S; Kazemi, A; Zarrinic, G; Morowvat, M H; Kargar, M

    2011-01-01

    Lipases are an important class of enzymes which catalyze the hydrolysis of long chain triglycerides and constitute the most prominent group ofbiocatalysts for biotechnological applications. There are a number of lipases, produced by some halophilic microorganisms. In this study, some lipase producing bacteria from Maharlu salt lake located in south of Iran were isolated. All isolates were screened for true lipase activity on plates containing olive oil. The lipase activity was measured using titrimetric methods. Among thirty three isolates, thirteen strains demonstrating orange zone around colonies under UV light, were selected for identification using the molecular methods and some morphological characteristics. The bacterium Bacillus vallismortis BCCS 007 with 3.41 +/- 0.14 U/mL lipase activity was selected as the highest lipase producing isolate. This is the first report of isolation and molecular identification of lipase producing bacteria from Maharlu lake. PMID:22073547

  19. Combined Insulin Deficiency and Endotoxin Exposure Stimulate Lipid Mobilization and Alter Adipose Tissue Signaling in an Experimental Model of Ketoacidosis in Subjects With Type 1 Diabetes: A Randomized Controlled Crossover Trial.

    Svart, Mads; Kampmann, Ulla; Voss, Thomas; Pedersen, Steen B; Johannsen, Mogens; Rittig, Nikolaj; Poulsen, Per L; Nielsen, Thomas S; Jessen, Niels; Møller, Niels

    2016-05-01

    Most often, diabetic ketoacidosis (DKA) in adults results from insufficient insulin administration and acute infection. DKA is assumed to release proinflammatory cytokines and stress hormones that stimulate lipolysis and ketogenesis. We tested whether this perception of DKA can be reproduced in an experimental human model by using combined insulin deficiency and acute inflammation and tested which intracellular mediators of lipolysis are affected in adipose tissue. Nine subjects with type 1 diabetes were studied twice: 1) insulin-controlled euglycemia and 2) insulin deprivation and endotoxin administration (KET). During KET, serum tumor necrosis factor-α, cortisol, glucagon, and growth hormone levels increased, and free fatty acids and 3-hydroxybutyrate concentrations and the rate of lipolysis rose markedly. Serum bicarbonate and pH decreased. Adipose tissue mRNA contents of comparative gene identification-58 (CGI-58) increased and G0/G1 switch 2 gene (G0S2) mRNA decreased robustly. Neither protein levels of adipose triglyceride lipase (ATGL) nor phosphorylations of hormone-sensitive lipase were altered. The clinical picture of incipient DKA in adults can be reproduced by combined insulin deficiency and endotoxin-induced acute inflammation. The precipitating steps involve the release of proinflammatory cytokines and stress hormones, increased lipolysis, and decreased G0S2 and increased CGI-58 mRNA contents in adipose tissue, compatible with latent ATGL stimulation. PMID:26884439

  20. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O2 for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  1. Modest hypoxia significantly reduces triglyceride content and lipid droplet size in 3T3-L1 adipocytes

    Hashimoto, Takeshi, E-mail: thashimo@fc.ritsumei.ac.jp [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Yokokawa, Takumi; Endo, Yuriko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Iwanaka, Nobumasa [Ritsumeikan Global Innovation Research Organization, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Higashida, Kazuhiko [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan); Faculty of Sport Science, Waseda University, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192 (Japan); Taguchi, Sadayoshi [Faculty of Sport and Health Science, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577 (Japan)

    2013-10-11

    Highlights: •Long-term hypoxia decreased the size of LDs and lipid storage in 3T3-L1 adipocytes. •Long-term hypoxia increased basal lipolysis in 3T3-L1 adipocytes. •Hypoxia decreased lipid-associated proteins in 3T3-L1 adipocytes. •Hypoxia decreased basal glucose uptake and lipogenic proteins in 3T3-L1 adipocytes. •Hypoxia-mediated lipogenesis may be an attractive therapeutic target against obesity. -- Abstract: Background: A previous study has demonstrated that endurance training under hypoxia results in a greater reduction in body fat mass compared to exercise under normoxia. However, the cellular and molecular mechanisms that underlie this hypoxia-mediated reduction in fat mass remain uncertain. Here, we examine the effects of modest hypoxia on adipocyte function. Methods: Differentiated 3T3-L1 adipocytes were incubated at 5% O{sub 2} for 1 week (long-term hypoxia, HL) or one day (short-term hypoxia, HS) and compared with a normoxia control (NC). Results: HL, but not HS, resulted in a significant reduction in lipid droplet size and triglyceride content (by 50%) compared to NC (p < 0.01). As estimated by glycerol release, isoproterenol-induced lipolysis was significantly lowered by hypoxia, whereas the release of free fatty acids under the basal condition was prominently enhanced with HL compared to NC or HS (p < 0.01). Lipolysis-associated proteins, such as perilipin 1 and hormone-sensitive lipase, were unchanged, whereas adipose triglyceride lipase and its activator protein CGI-58 were decreased with HL in comparison to NC. Interestingly, such lipogenic proteins as fatty acid synthase, lipin-1, and peroxisome proliferator-activated receptor gamma were decreased. Furthermore, the uptake of glucose, the major precursor of 3-glycerol phosphate for triglyceride synthesis, was significantly reduced in HL compared to NC or HS (p < 0.01). Conclusion: We conclude that hypoxia has a direct impact on reducing the triglyceride content and lipid droplet size via

  2. Investigations with tritium-labelled glycerol of the triglyceride metabolism in patients

    Triglycerides, being components of lipoproteins, are secreted by the liver into the blood and climinated from the blood by adipose and muscle tissue. The kinetics of this metabolic pathway were studied after injection of tritium-labelled glycerol which is incorporated into triglycerides by the liver. The serum triglyceride radioactivity-time curve was analysed with a computer. 99 examinations showed a decrease of the fractional turnover rate and an increase of the turnover rate with the triglyceride level. The test enables to decide whether an increased triglyceride concentration is caued by overproduction or by disturbed climination. (author)

  3. Optimization of conjugated linoleic acid triglycerides via enzymatic esterification in no-solvent system

    YI Dan; SUN Xiuqin; LI Guangyou; LIU Fayi; LIN Xuezheng; SHEN Jihong

    2009-01-01

    We compared four esterifiable enzymes. The lipase Novozym 435 possessed the highest activity for the conjugated linoleic acid esterification during the synthesis of triglycerides. The triglycerides were synthesized by esterification of glycerol and conjugated linoleic acid (CLA) in a no-solvent system using lipase catalysis. We investigated the effects of temperature, enzyme concentration, water content, and time on esterification. Enzyme and water concentrations of up to 1% of the total reaction volume and a system temperature of 60°C proved optimal for esterification. Similarly, when the esterification was carried out for 24 h, the reaction ratio improved to 94.11%. The esterification rate of the rotating screen basket remained high (87.28%) when the enzyme was re-used for the 5th time. We evaluated the substrate selectivity of lipase (NOVO 435) and determined that this lipase prefers the 10,12-octadacadienoic acid to the 9,11-octadecadienoic acid.

  4. Endothelial lipase is a major determinant of HDL level

    Ishida, Tatsuro; Choi, Sungshin; Kundu, Ramendra K.; Hirata, Ken-Ichi; Rubin, Edward M.; Cooper, Allen D.; Quertermous, Thomas

    2003-01-30

    For the past three decades, epidemiologic studies have consistently demonstrated an inverse relationship between plasma HDL cholesterol (HDL-C) concentrations and coronary heart disease (CHD). Population-based studies have provided compelling evidence that low HDL-C levels are a risk factor for CHD, and several clinical interventions that increased plasma levels of HDL-C were associated with a reduction in CHD risk. These findings have stimulated extensive investigation into the determinants of plasma HDL-C levels. Turnover studies using radiolabeled apolipoprotein A-I, the major protein component of HDL, suggest that plasma HDL-C concentrations are highly correlated with the rate of clearance of apolipoprotein AI. However, the metabolic mechanisms by which HDL are catabolized have not been fully defined. Previous studies in humans with genetic deficiency of cholesteryl ester transfer protein, and in mice lacking the scavenger receptor BI (SR-BI), have demonstrated that these proteins participate in the removal of cholesterol from HDL, while observations in individuals with mutations in hepatic lipase indicate that this enzyme hydrolyzes HDL triglycerides. In this issue of the JCI, reports from laboratories of Tom Quertermous and Dan Rader now indicate that endothelial lipase (LIPG), a newly identified member of the lipase family, catalyzes the hydrolysis of HDL phospholipids and facilitates the clearance of HDL from the circulation. Endothelial lipase was initially cloned by both of these laboratories using entirely different strategies. Quertermous and his colleagues identified endothelial lipase as a transcript that was upregulated in cultured human umbilical vein endothelial cells undergoing tube formation, whereas the Rader group cloned endothelial lipase as a transcript that was upregulated in the human macrophage-like cell line THP-1 exposed to oxidized LDL. Database searches revealed that endothelial lipase shows strong sequence similarity to lipoprotein

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

    Paula Renee Chen

    2016-03-01

    Full Text Available 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.

  6. Biosensor Applications of MAPLE Deposited Lipase

    Valeria Califano

    2014-10-01

    Full Text Available Matrix Assisted Pulsed Laser Evaporation (MAPLE is a thin film deposition technique derived from Pulsed Laser Deposition (PLD for deposition of delicate (polymers, complex biological molecules, etc. materials in undamaged form. The main difference of MAPLE technique with respect to PLD is the target: it is a frozen solution or suspension of the (guest molecules to be deposited in a volatile substance (matrix. Since laser beam energy is mainly absorbed by the matrix, damages to the delicate guest molecules are avoided, or at least reduced. Lipase, an enzyme catalyzing reactions borne by triglycerides, has been used in biosensors for detection of β-hydroxyacid esters and triglycerides in blood serum. Enzymes immobilization on a substrate is therefore required. In this paper we show that it is possible, using MAPLE technique, to deposit lipase on a substrate, as shown by AFM observation, preserving its conformational structure, as shown by FTIR analysis.

  7. USF1 deficiency activates brown adipose tissue and improves cardiometabolic health.

    Laurila, Pirkka-Pekka; Soronen, Jarkko; Kooijman, Sander; Forsström, Saara; Boon, Mariëtte R; Surakka, Ida; Kaiharju, Essi; Coomans, Claudia P; Van Den Berg, Sjoerd A A; Autio, Anu; Sarin, Antti-Pekka; Kettunen, Johannes; Tikkanen, Emmi; Manninen, Tuula; Metso, Jari; Silvennoinen, Reija; Merikanto, Krista; Ruuth, Maija; Perttilä, Julia; Mäkelä, Anne; Isomi, Ayaka; Tuomainen, Anita M; Tikka, Anna; Ramadan, Usama Abo; Seppälä, Ilkka; Lehtimäki, Terho; Eriksson, Johan; Havulinna, Aki; Jula, Antti; Karhunen, Pekka J; Salomaa, Veikko; Perola, Markus; Ehnholm, Christian; Lee-Rueckert, Miriam; Van Eck, Miranda; Roivainen, Anne; Taskinen, Marja-Riitta; Peltonen, Leena; Mervaala, Eero; Jalanko, Anu; Hohtola, Esa; Olkkonen, Vesa M; Ripatti, Samuli; Kovanen, Petri T; Rensen, Patrick C N; Suomalainen, Anu; Jauhiainen, Matti

    2016-01-27

    USF1 (upstream stimulatory factor 1) is a transcription factor associated with familial combined hyperlipidemia and coronary artery disease in humans. However, whether USF1 is beneficial or detrimental to cardiometabolic health has not been addressed. By inactivating USF1 in mice, we demonstrate protection against diet-induced dyslipidemia, obesity, insulin resistance, hepatic steatosis, and atherosclerosis. The favorable plasma lipid profile, including increased high-density lipoprotein cholesterol and decreased triglycerides, was coupled with increased energy expenditure due to activation of brown adipose tissue (BAT). Usf1 inactivation directs triglycerides from the circulation to BAT for combustion via a lipoprotein lipase-dependent mechanism, thus enhancing plasma triglyceride clearance. Mice lacking Usf1 displayed increased BAT-facilitated, diet-induced thermogenesis with up-regulation of mitochondrial respiratory chain complexes, as well as increased BAT activity even at thermoneutrality and after BAT sympathectomy. A direct effect of USF1 on BAT activation was demonstrated by an amplified adrenergic response in brown adipocytes after Usf1 silencing, and by augmented norepinephrine-induced thermogenesis in mice lacking Usf1. In humans, individuals carrying SNP (single-nucleotide polymorphism) alleles that reduced USF1 mRNA expression also displayed a beneficial cardiometabolic profile, featuring improved insulin sensitivity, a favorable lipid profile, and reduced atherosclerosis. Our findings identify a new molecular link between lipid metabolism and energy expenditure, and point to the potential of USF1 as a therapeutic target for cardiometabolic disease. PMID:26819196

  8. Expression of lipases and lipid receptors in sperm storage tubules and possible role of fatty acids in sperm survival in the hen oviduct.

    Huang, A; Isobe, N; Obitsu, T; Yoshimura, Y

    2016-04-15

    The aim of this study was to determine the role of fatty acids for sperm survival in the sperm storage tubules (SSTs) of the hen oviduct. The mucosa tissues of uterovaginal junction (UVJ) of White Leghorn laying hens with or without artificial insemination using semen from Barred Plymouth Rock roosters were collected. The lipid density in the epithelium of UVJ and SST was analyzed by Sudan black B staining. The expressions of genes encoding lipid receptors and lipases were assayed by polymerase chain reaction in UVJ mucosa and SST cells isolated by laser microdissection. Fatty acid composition was analyzed by gas chromatography, and sperm were cultured with or without the identified predominant fatty acids for 24 hours to examine their effect on sperm viability. The lipid droplets were localized in the epithelium of UVJ mucosa and SSTs. The expression of genes encoding very low-density lipoprotein receptor(VLDLR), low-density lipoprotein receptor (LDLR), and fatty acid translocase (FAT/CD36) were found in SST cells. Expression of genes encoding endothelial lipase (EL), lipase H (LIPH), adipose triglyceride lipase (ATGL), and lipoprotein lipase (LPL) were found in UVJ. In contrast, only ATGL was found in SST cells, and its expression was significantly upregulated after artificial insemination. In UVJ mucosal tissues, five fatty acids, namely myristic acid (C14), palmitic acid (C16), stearic acid (C18), oleic acid (C18:1n9), and linoleic acid (C18:2n6), were identified as predominant fatty acids. The viability of sperm cultured with 1 mM oleic acid or linoleic acid was significantly higher than the sperm in the control culture without fatty acids. These results suggest that lipids in the SST cells may be degraded by ATGL, and fatty acids including oleic acid and linoleic acid may be released into the SST lumen to support sperm survival. PMID:26777559

  9. Optimasi Produksi Enzim Lipase dari Bakteri Sumber Air Panas Tamalantik, Mamasa Sulawesi Barat

    Tunggala, Stephanie; Natsir, Hasnah; Hariani, Nunuk

    2014-01-01

    Lipase (EC 3.1.1.3) is one of class hydrolase enzymes that can hydrolyze triglycerides into fatty acids and glycerol. This research determine the optimum conditions of lipase production from Bacillus isolates sp.TM_2a.2 which isolated from hot spring Tamalantik, Mamasa, West Celebes with Various of substrat concentration (olive oil) is 0.2%, 0.4%, 0, 6%, 0.8% and 1%. The activity of lipase production was tested by titrimetric method. The results show that the lipase produced optimum at subst...

  10. Familial lipoprotein lipase deficiency

    ... medlineplus.gov/ency/article/000408.htm Familial lipoprotein lipase deficiency To use the sharing features on this page, please enable JavaScript. Familial lipoprotein lipase deficiency is a group of rare genetic disorders ...

  11. Study of enzymatic reactors with microencapsulated lipase. Doctoral thesis. Estudo de reactores enzimaticos com lipase microencapsulada

    de Franca Teixeira dos Prazeres, D.M.

    1992-10-01

    The work reports the development of a membrane reactor for the hydrolysis of triglycerides catalyzed by lipase B from Chromobacterium viscosum in AOT/isooctane reversed miceller system. In a preliminary phase the potential of the organic system was evaluated with comparative studies on the activity and stability of lipase B in aqueous media (emulsion) and in the alternative miceller media. A tubular ceramic membrane reactor with recirculation was selected for the olive oil hydrolysis in a reversed miceller system. The influence of the hydration degree, recirculation rate, AOT, olive oil and lipase concentration in the operation of the reactor were investigated in a batch mode. The hydration degree was identified as a critical parameter due to its influence in the separation process and in the kinetics of the reaction.

  12. Lipoprotein lipase deficiency.

    Shankar K; Bava H; Shetty J; Joshi M

    1997-01-01

    A rare case of a 3 month old child with lipoprotein lipase deficiency who presented with bronchopneumonia is reported. After noticing lipaemic serum and lipaemia retinalis, a diagnosis of hyperlipoproteinaemia was considered. Lipoprotein lipase deficiency was confirmed with post heparin lipoprotein lipase enzyme activity estimation.

  13. The specificity of Several Kinds Lipases on n-3 Polyunsaturated Fatty Acids

    Jenny Elisabeth, T Yuliani, P M Tambunan, J M Purba

    2001-04-01

    Full Text Available Several lipases from microbial and plant, i.e Rhizomucor miehei, Pseudomonas sp., Candida antartica, rice bran, and Carica papaya latex (CPL were examined for synthesis of omega-3 (n-3 PUFA-rich glyceride by hydrolysis and acidolysis reaction. Tuna oil was used in hydrolysis reaction, whereas tuna and palm oils were used as source of triglyceride (TAG molecules and n-3 PUFA concentrate from tuna oil as source of EPA and DHA in acidolysis reaction.For hydrolysis reaction, the rice bran and CPL lipases showed the lowest hydrolytic activity of the tuna oil, whereas the R. miehei lipase showed the highest hydrolytic activity but was unable to hydrolyze EPA and DHA. On the contrary, the C. antartica and Pseudomonas sp. lipases acted stronger on hydrolysis of DHA ester bond than EPA.For acidolysis reaction, all the lipases showed ability to incorporate n-3 PUFA into tuna and palm oils. C. antartica lipase had the maximum DHA incorporation into tuna and palm oils, rice bran lipase had relatively similar ability with R. miehei lipase, and the CPL lipase had the lowest ability. This study proved that rice bran and CPL lipases also had transesterification activity and showed the feasibility of the rice bran lipase to be a biocatalyst for n-3 PUFA-rich glyceride production. Increasing the substrate ratio, of n-3 PUFA concentrate and tuna or palm oil, could increase the EPA and DHA incorporation. The R. miehei, rice bran, and CPL lipases unabled to incorporate DHA into DHA-containing glyceride molecule, whereas C. antartica lipase had the capability in high ratio of n-3 PUFA concentrate to oil. Therefore, the lipases were easier to incorporate n-3 PUFA into palm oil than tuna oil, since the TAG molecules of palm oil was not as complex as tuna oil. It could be suggested that the lipases did not only have acyl chain and positional specificity, but also the whole glyceride structure specificity.

  14. High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle.

    Badin, Pierre-Marie; Vila, Isabelle K; Louche, Katie; Mairal, Aline; Marques, Marie-Adeline; Bourlier, Virginie; Tavernier, Geneviève; Langin, Dominique; Moro, Cedric

    2013-04-01

    Elevated expression/activity of adipose triglyceride lipase (ATGL) and/or reduced activity of hormone-sensitive lipase (HSL) in skeletal muscle are causally linked to insulin resistance in vitro. We investigated here the effect of high-fat feeding on skeletal muscle lipolytic proteins, lipotoxicity, and insulin signaling in vivo. Five-week-old C3H mice were fed normal chow diet (NCD) or 45% kcal high-fat diet (HFD) for 4 weeks. Wild-type and HSL knockout mice fed NCD were also studied. Whole-body and muscle insulin sensitivity, as well as lipolytic protein expression, lipid levels, and insulin signaling in skeletal muscle, were measured. HFD induced whole-body insulin resistance and glucose intolerance and reduced skeletal muscle glucose uptake compared with NCD. HFD increased skeletal muscle total diacylglycerol (DAG) content, protein kinase Cθ and protein kinase Cε membrane translocation, and impaired insulin signaling as reflected by a robust increase of basal Ser1101 insulin receptor substrate 1 phosphorylation (2.8-fold, P < .05) and a decrease of insulin-stimulated v-Akt murine thymoma viral oncogene homolog Ser473 (-37%, P < .05) and AS160 Thr642 (-47%, P <.01) phosphorylation. We next showed that HFD strongly reduced HSL phosphorylation at Ser660. HFD significantly up-regulated the muscle protein content of the ATGL coactivator comparative gene identification 58 and triacylglycerol hydrolase activity, despite a lower ATGL protein content. We further show a defective skeletal muscle insulin signaling and DAG accumulation in HSL knockout compared with wild-type mice. Together, these data suggest a pathophysiological link between altered skeletal muscle lipase expression and DAG-mediated insulin resistance in mice. PMID:23471217

  15. Homology of lipoprotein lipase to pancreatic lipase.

    Ben-Avram, C M; Ben-Zeev, O; Lee, T.D. (Taunia D.); Haaga, K; Shively, J. E.; Goers, J; Pedersen, M.E; Reeve, J R; Schotz, M C

    1986-01-01

    Bovine milk lipoprotein lipase was subjected to amino acid sequence analysis. The first 19 amino-terminal residues were Asp-Arg-Ile-Thr-Gly-Gly-Lys-Asp-Phe-Arg-Asp-Ile-Glu-Ser-Lys-Phe-Ala-Leu- Arg. In addition, reversed-phase high-performance liquid chromatography of a tryptic digest of reduced and alkylated lipase resolved a number of peptides, five of which contained cysteine. Sequence analysis of the tryptic peptides revealed in most instances a close homology to porcine pancreatic lipase....

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

    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.

  17. Evaluation of a New Lipase from Staphylococcus sp. for Detergent Additive Capability

    Mamta Chauhan

    2013-01-01

    Full Text Available Lipases are the enzymes of choice for laundry detergent industries owing to their triglyceride removing ability from the soiled fabric which eventually reduces the usage of phosphate-based chemical cleansers in the detergent formulation. In the present study, a partially purified bacterial lipase from Staphylococcus arlettae JPBW-1 isolated from the rock salt mine has been assessed for its triglyceride removing ability by developing a presoak solution so as to use lipase as an additive in laundry detergent formulations. The effects of selected surfactants, commercial detergents, and oxidizing agents on lipase stability were studied in a preliminary evaluation for its further usage in the industrial environment. Partially purified lipase has shown good stability in presence of surfactants, commercial detergents, and oxidizing agents. Washing efficiency has been found to be enhanced while using lipase with 0.5% nonionic detergent than the anioinic detergent. The wash performance using 0.5% wheel with 40 U lipase at 40°C in 45 min results in maximum oil removal (62% from the soiled cotton fabric. Hence, the present study opens the new era in enzyme-based detergent sector for formulation of chemical-free detergent using alkaline bacterial lipase.

  18. Structure of product-bound SMG1 lipase: active site gating implications.

    Guo, Shaohua; Xu, Jinxin; Pavlidis, Ioannis V; Lan, Dongming; Bornscheuer, Uwe T; Liu, Jinsong; Wang, Yonghua

    2015-12-01

    Monoacylglycerol and diacylglycerol lipases are industrially interesting enzymes, due to the health benefits that arise from the consumption of diglycerides compared to the traditional triglyceride oils. Most lipases possess an α-helix (lid) directly over the catalytic pocket which regulates the activity of the enzyme. Generally, lipases exist in active and inactive conformations, depending on the positioning of this lid subdomain. However, lipase SMG1, a monoacylglycerol and diacylglycerol specific lipase, has an atypical activation mechanism. In the present study we were able to prove by crystallography, in silico analysis and activity tests that only two positions, residues 102 and 278, are responsible for a gating mechanism that regulates the active and inactive states of the lipase, and that no significant structural changes take place during activation except for oxyanion hole formation. The elucidation of the gating effect provided data enabling the rational design of improved lipases with 6-fold increase in the hydrolytic activity toward diacylglycerols, just by providing additional substrate stabilization with a single mutation (F278N or F278T). Due to the conservation of F278 among the monoacylglycerol and diacylglycerol lipases in the Rhizomucor miehei lipase-like family, the gating mechanism described herein might represent a general mechanism applicable to other monoacylglycerol and diacylglycerol lipases as well. Database: Structural data are available in the Protein Data Bank under the accession numbers 4ZRE (F278D mutant) and 4ZRD (F278N mutant). PMID:26365206

  19. NEW LIPASE-PRODUCERS MICROORGANISMS FROM PERUVIAN AMAZONIA WHICH HYDROLYZE PALM OIL AND DERIVATIVES

    Roxana Trujillo

    2014-04-01

    Full Text Available Two yeasts: Cryptococcus uchicensis TMY9 and Pichia uchicensis TMY10 and one fungus Verticillium tingalensis TMFMB are described for the first time as lipase producer microorganisms. The strains have been isolated after an ecological screening in a palm oil industry. The yeasts- C. uchicensis and Pichia uchicensis - mainly produce extracellular lipases as active as those produced by traditional lipase producing microorganisms. The extracellular lipases are active in the hydrolysis of crude palm oil and its industrial derivatives. Contrarily in the isolated fungus, the lipase mainly remains bonded to biomass. In all cases, greater hydrolytic activities are observed in the hydrolysis of palm olein and super-olein than with saturated substrates as stearine. P. uchicensis lipase shows moderated selectivity versus saturated acid triglycerides compared to substrates with high proportion of oleic acid (olein or superolein. The opposite behavior is observed with C. uchicensis and fungal lipases. P. uchicensis produces a more active crude lipase than C. uchicensis with lower biomass production. The kinetic runs performed with crude yeast lipases suggest a three steps mechanism where the high penetration of lipase in the fat gouts favors the hydrolysis.

  20. m-DOPA addition in MAPLE immobilization of lipase for biosensor applications

    Valeria Califano; Giovanni Ausanio; Francesco Bloisi; Antonio Aronne; Luciano R.M. Vicari; Libera Nasti

    2015-01-01

    Matrix Assisted Pulsed Laser Evaporation (MAPLE) is a thin film deposition technique which uses a pulsed laser beam impinging, inside a high vacuum chamber, on a frozen target containing the guest molecules in a volatile matrix to induce fast “evaporation” of the matrix, and ejection of the guest molecules. Lipase, an enzyme acting as a catalyst in hydrolysis of lipids, is widely used in biosensors for detection of triglycerides in blood serum. A key action to this purpose is lipase immobiliz...

  1. Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

    Landis, B.A.; Rotolo, F.S.; Meyers, W.C.; Clark, A.B.; Quarfordt, S.H.

    1987-06-01

    The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound.

  2. Influences of apolipoprotein E on soluble and heparin-immobilized hepatic lipase

    The effect of human apolipoprotein E (apoE), either alone or in combination with apoC, on the lipolysis of a radiolabeled triglyceride emulsion was studied with hepatic lipase in solution and immobilized on heparin-Sepharose. The soluble hepatic lipase was inhibited, whereas the heparin-immobilized lipase was stimulated by apoE. This stimulation was attenuated by combining apoE with either apoC-II or C-III. The heparin-immobilized lipase demonstrated much less lipolysis of the zwitterionic phosphatidylcholine-stabilized triglyceride emulsion than did the soluble enzyme. This difference was less when the emulsion was stabilized by a nonionic detergent. apoE inhibited lipase activity when assayed under conditions (0.4 M NaCl) of bound enzyme and unbound substrate. Increasing the emulsion apoE content beyond optimum inhibited lipolysis by the immobilized enzyme. Kinetic analysis of phosphatidylcholine-stabilized triglyceride emulsions revealed a significant decrease in immobilized enzyme K/sub m/ and an increase in V/sub max/ when the emulsion was supplemented with apoE. Distributing the immobilized lipase in clustered aggregates produced more lipolysis than when the same enzyme content was uniformly bound

  3. Lysosomal acid lipase deficiency in rats: Lipid analyses and lipase activities in liver and spleen

    We report the biological characterization of an animal model of a genetic lipid storage disease analogous to human Wolman's disease. Affected rats accumulated cholesteryl esters (13.3-fold), free cholesterol (2.8-fold), and triglycerides (5.4-fold) in the liver, as well as cholesteryl esters (2.5-fold) and free cholesterol (1.33-fold) in the spleen. Triglycerides did not accumulate, and the levels actually decreased in the spleen. Analysis of the fatty acid composition of the cholesteryl esters and triglycerides showed high percentages of linoleic acid (18:2) and arachidonic acid (20:4) in both organs, especially in the liver. No accumulation of phospholipids, neutral glycosphingolipids, or gangliosides was found in the affected rats. Acid lipase activity for [14C]triolein, [14C]cholesteryl oleate, and 4-methyl-umbelliferyl oleate was deficient in both the liver and spleen of affected rats. Lipase activity at neutral pH was normal in both liver and spleen. Heterozygous rats showed intermediate utilization of these substrates in both organs at levels between those for affected rats and those for normal controls, although they did not accumulate any lipids. These data suggest that these rats represent an animal counterpart of Wolman's disease in humans

  4. Interaction of rat hormone-sensitive lipase with adipocyte lipid-binding protein

    Shen, Wen-Jun; Sridhar, Kunju; Bernlohr, David A.; Fredric B Kraemer

    1999-01-01

    Hormone-sensitive lipase (HSL) is a cytosolic neutral lipase that functions as the rate-limiting enzyme for the mobilization of free fatty acids in adipose tissue. By using the yeast two-hybrid system to examine the potential interaction of HSL with other cellular proteins, evidence is provided to demonstrate a direct interaction of HSL with adipocyte lipid-binding protein (ALBP), a member of the family of intracellular lipid-binding proteins that binds fatty acids, retinoids, and other hydro...

  5. High-throughput virtual screening with e-pharmacophore and molecular simulations study in the designing of pancreatic lipase inhibitors

    Veeramachaneni GK

    2015-08-01

    Full Text Available Ganesh Kumar Veeramachaneni, K Kranthi Raj, Leela Madhuri Chalasani, Jayakumar Singh Bondili, Venkateswara Rao Talluri Department of Biotechnology, K L University, Guntur, India Background: Obesity is a progressive metabolic disorder in the current world population, and is characterized by the excess deposition of fat in the adipose tissue. Pancreatic lipase is one of the key enzymes in the hydrolysis of triglycerides into monoglycerides and free fatty acids, and is thus considered a promising target for the treatment of obesity. The present drugs used for treating obesity do not give satisfactory results, and on prolonged usage result in severe side effects. In view of the drastic increase in the obese population day-to-day, there is a greater need to discover new drugs with lesser side effects.Materials and methods: High-throughput virtual screening combined with e-pharmacophore screening and ADME (absorption, distribution, metabolism, and excretion and PAINS (pan-assay interference compounds filters were applied to screen out the ligand molecules from the ZINC natural molecule database. The screened molecules were subjected to Glide XP docking to study the molecular interactions broadly. Further, molecular dynamic simulations were used to validate the stability of the enzyme–ligand complexes. Finally, the molecules with better results were optimized for in vitro testing.Results: The screening protocols identified eight hits from the natural molecule database, which were further filtered through pharmacological filters. The final four hits were subjected to extra precision docking, and the complexes were finally studied with molecular dynamic simulations. The results pointed to the zinc 85893731 molecule as the most stable in the binding pocket, producing consistent H-bond interaction with Ser152 (G=-7.18. The optimized lead molecule exhibited good docking score, better fit, and improved ADME profile.Conclusion: The present study specifies

  6. Les lipases sont des hydrolases atypiques : principales caractéristiques et applications

    Fickers P.

    2008-01-01

    Full Text Available ipases are atypical hydrolases: principal characteristics and applications. Due to their kinetic and substrate specificities, triacylglycerol acyl-hydrolases or lipases are atypical enzymes. In function of their microenvironment, lipases are able to act as hydrolases in aqueous solution or as biocatalysts in organic synthesis. As hydrolases, they are responsible of the triglycerids catabolism into fatty acids and glycerol. In many organisms, this reaction plays a major role in the fat and lipid metabolism. In addition, lipases are also able to hydrolyse phospholipids and cholesterol esters. In organic solvent, lipases could catalyse reactions such as esterifications, acidolysis or alcoolysis with enantio-, regio- and chimioselectivity. Lipases form a mixed class of enzyme due to their animal, vegetal or microbial origins. All those properties led to the development of many applications in the food and chemical industries but also in the medical and therapeutic field.

  7. Strategies to Characterize Fungal Lipases for Applications in Medicine and Dairy Industry

    Subash C. B. Gopinath

    2013-01-01

    Full Text Available Lipases are water-soluble enzymes that act on insoluble substrates and catalyze the hydrolysis of long-chain triglycerides. Lipases play a vital role in the food, detergent, chemical, and pharmaceutical industries. In the past, fungal lipases gained significant attention in the industries due to their substrate specificity and stability under varied chemical and physical conditions. Fungal enzymes are extracellular in nature, and they can be extracted easily, which significantly reduces the cost and makes this source preferable over bacteria. Soil contaminated with spillage from the products of oil and dairy harbors fungal species, which have the potential to secrete lipases to degrade fats and oils. Herein, the strategies involved in the characterization of fungal lipases, capable of degrading fatty substances, are narrated with a focus on further applications.

  8. Acid lipase from Candida viswanathii: production, biochemical properties, and potential application.

    de Almeida, Alex Fernando; Tauk-Tornisielo, Sâmia Maria; Carmona, Eleonora Cano

    2013-01-01

    Influences of environmental variables and emulsifiers on lipase production of a Candida viswanathii strain were investigated. The highest lipase activity (101.1 U) was observed at 210 rpm, pH 6.0, and 27.5°C. Other fermentation parameters analyzed showed considerable rates of biomass yield (Y L/S = 1.381 g/g), lipase yield (Y L/S = 6.892 U/g), and biomass productivity (P X = 0.282 g/h). Addition of soybean lecithin increased lipase production in 1.45-fold, presenting lipase yield (Y L/S ) of 10.061 U/g. Crude lipase presented optimal activity at acid pH of 3.5, suggesting a new lipolytic enzyme for this genus and yeast in general. In addition, crude lipase presented high stability in acid conditions and temperature between 40 and 45°C, after 24 h of incubation in these temperatures. Lipase remained active in the presence of organic solvents maintaining above 80% activity in DMSO, methanol, acetonitrile, ethanol, acetone, 1-propanol, isopropanol, and 2-propanol. Effectiveness for the hydrolysis of a wide range of natural triglycerides suggests that this new acid lipase has high potential application in the oleochemical and food industries for hydrolysis and/or modification of triacylglycerols to improve the nutritional properties. PMID:24350270

  9. Alterations in Adipose Tissue during Critical Illness: An Adaptive and Protective Response?

    Langouche, Lies; Vander Perre, Sarah; Thiessen, Steven; Gunst, Jan; Hermans, Greet; D'Hoore, André; Kola, Blerina; Korbonits, Márta; Van den Berghe, Greet

    2010-01-01

    Rationale: Critical illness is characterized by lean tissue wasting, whereas adipose tissue is preserved. Overweight and obese critically ill patients may have a lower risk of death than lean patients, suggestive of a protective role for adipose tissue during illness. Objectives: To investigate whether adipose tissue could protectively respond to critical illness by storing potentially toxic metabolites, such as excess circulating glucose and triglycerides. Methods: We studied adipose tissue ...

  10. Serum lipoprotein lipase mass: Clinical significance of its measurement

    Kobayashi, Junji; Nohara, Atsushi; Kawashiri, Masaaki; Inazu, Akihiro; Koizumi, Junji; Nakajima, Katsuyuki; Mabuchi, Hiroshi

    2007-01-01

    Lipoprotein lipase (LPL) is a lipolytic enzyme involved in catalyzing hydrolysis of triglycerides (TG) in chylomicrons and very low-density lipoprotein (VLDL) particles. Over the last decade, increasing attention has been paid to the clinical significance of measuring serum LPL protein mass without heparin injection to the study subjects. In earlier studies, this marker was utilized to classify LPL deficient subjects, which is an extremely rare metabolic disorder with a frequency of one in on...

  11. Lipoprotein lipase links dietary fat to solid tumor cell proliferation

    Kuemmerle, Nancy B.; Rysman, Evelien; Lombardo, Portia S.; Flanagan, Alison J.; Lipe, Brea C.; Wells, Wendy A.; Pettus, Jason R.; Froehlich, Heather M.; Memoli, Vincent A.; Morganelli, Peter M.; Swinnen, Johannes V.; Timmerman, Luika A.; Chaychi, Leila; Fricano, Catherine J.; Eisenberg, Burton L.

    2011-01-01

    Many types of cancer cells require a supply of fatty acids (FA) for growth and survival, and interrupting de novo FA synthesis in model systems causes potent anticancer effects. We hypothesized that, in addition to synthesis, cancer cells may obtain pre-formed, diet-derived fatty acids by uptake from the bloodstream. This would require hydrolytic release of FA from triglyceride in circulating lipoprotein particles by the secreted enzyme lipoprotein lipase (LPL), and the expression of CD36, th...

  12. Lipase-catalyzed biodiesel synthesis with different acyl acceptors

    Ognjanović Nevena D.

    2008-01-01

    Full Text Available Biodiesel is an alternative fuel for diesel engine that is environmentally acceptable. Conventionally, biodiesel is produced by transesterification of triglycerides and short alcohols in the presence of an acid or an alkaline catalyst. There are several problems associated with this kind of production that can be resolved by using lipase as the biocatalyst. The aim of the present work was to investigate novel acyl acceptors for biodiesel production. 2-Propanol and n-butanol have a less negative effect on lipase stability, and they also improve low temperature properties of the fuel. However, excess alcohol leads to inactivation of the enzyme, and glycerol, a major byproduct, can block the immobilized enzyme, resulting in low enzymatic activity. This problem was solved by using methyl acetate as acyl acceptor. Triacetylglycerol is produced instead of glycerol, and it has no negative effect on the activity of the lipase.

  13. Does the Pancreas Really Produce Much More Lipase than Required for Fat Digestion?

    Sander-Struckmeier S

    2005-05-01

    Full Text Available Thirty years ago, it was reported that a linear relationship does not exist between the amounts of human pancreatic lipase secreted in chronic pancreatitis and the degree of steatorrhea, which was considered to appear only after more than 90% of the pancreatic secretory capacity had been lost. From these observations, it was generally thought that the lipolytic potential of the pancreas is much higher than required. In recent years, however, it has been noted that: 1 the level of inhibition of digestive lipases and gastrointestinal lipolysis by the lipase inhibitor orlistat were almost linearly correlated with the amount of excreted fat; 2 in minipigs with experimentally-induced pancreatic exocrine insufficiency, the amounts of enteric-coated pancreatic extracts needed for restoring fat digestion to normal levels were estimated to be much higher than those usually administered; 3 human pancreatic lipase specific activity on meal triglycerides is 3 orders of magnitude lower than the very high specific activity usually measured under experimental in vitro conditions which are far from physiological conditions; 4 in patients with reduced human pancreatic lipase secretion, gastric lipase plays a significant role in fat digestion. This last observation might explain the absence of a linear relationship between human pancreatic lipase secretion in chronic pancreatitis and steatorrhea. From the low specific activity displayed by human pancreatic lipase on meal triglycerides, one can better understand why more lipase than expected is needed, why fat digestion lasts for more than a few minutes and, finally, why there is not such an excess secretory capacity for lipase as had been previously thought.

  14. Autocrine function of aldehyde dehydrogenase 1 as a determinant of diet- and sex-specific differences in visceral adiposity.

    Yasmeen, Rumana; Reichert, Barbara; Deiuliis, Jeffrey; Yang, Fangping; Lynch, Alisha; Meyers, Joseph; Sharlach, Molly; Shin, Sangsu; Volz, Katharina S; Green, Kari B; Lee, Kichoon; Alder, Hansjuerg; Duester, Gregg; Zechner, Rudolf; Rajagopalan, Sanjay; Ziouzenkova, Ouliana

    2013-01-01

    Mechanisms for sex- and depot-specific fat formation are unclear. We investigated the role of retinoic acid (RA) production by aldehyde dehydrogenase 1 (Aldh1a1, -a2, and -a3), the major RA-producing enzymes, on sex-specific fat depot formation. Female Aldh1a1(-/-) mice, but not males, were resistant to high-fat (HF) diet-induced visceral adipose formation, whereas subcutaneous fat was reduced similarly in both groups. Sexual dimorphism in visceral fat (VF) was attributable to elevated adipose triglyceride lipase (Atgl) protein expression localized in clusters of multilocular uncoupling protein 1 (Ucp1)-positive cells in female Aldh1a1(-/-) mice compared with males. Estrogen decreased Aldh1a3 expression, limiting conversion of retinaldehyde (Rald) to RA. Rald effectively induced Atgl levels via nongenomic mechanisms, demonstrating indirect regulation by estrogen. Experiments in transgenic mice expressing an RA receptor response element (RARE-lacZ) revealed HF diet-induced RARE activation in VF of females but not males. In humans, stromal cells isolated from VF of obese subjects also expressed higher levels of Aldh1 enzymes compared with lean subjects. Our data suggest that an HF diet mediates VF formation through a sex-specific autocrine Aldh1 switch, in which Rald-mediated lipolysis in Ucp1-positive visceral adipocytes is replaced by RA-mediated lipid accumulation. Our data suggest that Aldh1 is a potential target for sex-specific antiobesity therapy. PMID:22933113

  15. Triglycerides in the human kidney cortex: relationship with body size.

    Ion Alexandru Bobulescu

    Full Text Available Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04. Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.

  16. Triglyceride-Rich Lipoproteins and Remnants: Targets for Therapy?

    Dallinga-Thie, Geesje M; Kroon, Jeffrey; Borén, Jan; Chapman, M John

    2016-07-01

    It is now evident that elevated circulating levels of triglycerides in the non-fasting state, a marker for triglyceride (TG)-rich remnant particles, are associated with increased risk of premature cardiovascular disease (CVD). Recent findings from basic and clinical studies have begun to elucidate the mechanisms that contribute to the atherogenicity of these apoB-containing particles. Here, we review current knowledge of the formation, intravascular remodelling and catabolism of TG-rich lipoproteins and highlight (i) the pivotal players involved in this process, including lipoprotein lipase, glycosylphosphatidylinositol HDL binding protein 1 (GPIHBP1), apolipoprotein (apo) C-II, apoC-III, angiopoietin-like protein (ANGPTL) 3, 4 and 8, apoA-V and cholesteryl ester transfer protein; (ii) key determinants of triglyceride (TG) levels and notably rates of production of very-low-density lipoprotein 1 (VLDL1) particles; and (iii) the mechanisms which underlie the atherogenicity of remnant particles. Finally, we emphasise the polygenic nature of moderate hypertriglyceridemia and briefly discuss modalities for its clinical management. Several new therapeutic strategies to attenuate hypertriglyceridemia have appeared recently, among which those targeted to apoC-III appear to hold considerable promise. PMID:27216847

  17. Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes.

    Kern, P A; Marshall, S; Eckel, R H

    1985-01-01

    To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific 125I-insulin binding. In addition, chloroquine induced an increase in cell-asso...

  18. Impact of dietary protein on lipid metabolism-related gene expression in porcine adipose tissue

    Ge Changrong

    2010-01-01

    Full Text Available Abstract Background High dietary protein can reduce fat deposition in animal subcutaneous adipose tissue, but little is known about the mechanism. Methods Sixty Wujin pigs of about 15 kg weight were fed either high protein (HP: 18% or low protein (LP: 14% diets, and slaughtered at body weights of 30, 60 or 100 kg. Bloods were collected to measure serum parameters. Subcutaneous adipose tissues were sampled for determination of adipocyte size, protein content, lipid metabolism-related gene expression, and enzyme activities. Results HP significantly reduced adipocyte size, fat meat percentage and backfat thickness, but significantly increased daily gain, lean meat percentage and loin eye area at 60 and 100 kg. Serum free fatty acid and triglyceride concentrations in the HP group were significantly higher than in the LP group. Serum glucose and insulin concentrations were not significantly affected by dietary protein at any body weight. HP significantly reduced gene expression of acetyl CoA carboxylase (ACC, fatty acid synthase (FAS and sterol regulatory element binding protein 1c (SREBP-1c at 60 kg and 100 kg; however, the mRNA level and enzyme activity of FAS were increased at 30 kg. HP promoted gene and protein expression and enzyme activities of lipoprotein lipase (LPL, carmitine palmtoyltransferase-1B (CPT-1B, peroxisome proliferator-activated receptor γ (PPARγ and adipocyte-fatty acid binding proteins (A-FABP at 60 kg, but reduced their expression at 100 kg. Gene expression and enzyme activity of hormone sensitive lipase (HSL was reduced markedly at 60 kg but increased at 100 kg by the high dietary protein. Levels of mRNA, enzyme activities and protein expression of ACC, FAS, SREBP-1c and PPARγ in both LP and HP groups increased with increasing body weight. However, gene and protein expression levels/enzyme activities of LPL, CPT-1B, A-FABP and HSL in both groups were higher at 60 kg than at 30 and 100 kg. Conclusion Fat deposition in Wujin

  19. Acid Lipase from Candida viswanathii: Production, Biochemical Properties, and Potential Application

    Alex Fernando de Almeida

    2013-01-01

    Full Text Available Influences of environmental variables and emulsifiers on lipase production of a Candida viswanathii strain were investigated. The highest lipase activity (101.1 U was observed at 210 rpm, pH 6.0, and 27.5°C. Other fermentation parameters analyzed showed considerable rates of biomass yield ( g/h. Addition of soybean lecithin increased lipase production in 1.45-fold, presenting lipase yield ( of 10.061 U/g. Crude lipase presented optimal activity at acid pH of 3.5, suggesting a new lipolytic enzyme for this genus and yeast in general. In addition, crude lipase presented high stability in acid conditions and temperature between 40 and 45°C, after 24 h of incubation in these temperatures. Lipase remained active in the presence of organic solvents maintaining above 80% activity in DMSO, methanol, acetonitrile, ethanol, acetone, 1-propanol, isopropanol, and 2-propanol. Effectiveness for the hydrolysis of a wide range of natural triglycerides suggests that this new acid lipase has high potential application in the oleochemical and food industries for hydrolysis and/or modification of triacylglycerols to improve the nutritional properties.

  20. Assaying lipase activity from oil palm fruit (Elaeis guineensis Jacq.) mesocarp.

    Ngando Ebongue, G F; Dhouib, R; Carrière, F; Amvam Zollo, P-H; Arondel, V

    2006-10-01

    The mesocarp of mature oil palm fruit undergoes intensive triglycerides hydrolysis upon abscission and bruising. This generates such a high amount of free fatty acids that the oil might become unfit for human consumption without appropriate refining. The lipase (EC 3.1.1.3) involved in the breakdown of the oil is not stable after homogenization of the tissue in aqueous buffers. In this study, we have devised a solvent-based procedure that allowed us to obtain fractions with stable lipase activity. Using these fractions, we have determined the optimal conditions for assaying mesocarp lipase activity. The activity was highest at a temperature of 35 degrees C and a pH of 9. The lipase was found to be strictly calcium dependent. The specific activity of the lipase measured in optimal conditions was found to be 33 mumol fatty acids released min(-1) mg(-1) protein using olive oil as substrate. The mesocarp contains about 190 U of lipase g(-1) fresh weight. This activity was found to be inhibited by the lipase inhibitor tetrahydrolipstatin (THL), suggesting that the lipase is a serine hydrolase. PMID:17064925

  1. Utilization of immobilized lipases as catalysts in the transesterification of non-edible vegetable oils with ethanol

    P. C. Tiosso; A. K. F. Carvalho; H. F. de Castro; F.F. de Moraes; G. M. Zanin

    2014-01-01

    This work reports the use of commercially available immobilized lipase preparations (Novozym® 435 and Lipozyme TL IM, both from Novozymes, and Lipase PS IM from Amano) as catalysts in the transesterification reaction of different alkyl-chain triglycerides with ethanol. The ethanolysis of native oils from Brazilian Amazon plants andiroba (Carapa guianensis), babassu (Orbignya sp.), jatropa (Jatropha curcas), and palm (Elaeis sp.) was studied in a solvent-free system. In a typical reaction, the...

  2. A Sequence Variation (I148M) in PNPLA3 Associated with Nonalcoholic Fatty Liver Disease Disrupts Triglyceride Hydrolysis*

    He, Shaoqing; McPhaul, Christopher; Li, John Zhong; Garuti, Rita; Kinch, Lisa; Nick V Grishin; Cohen, Jonathan C.; Hobbs, Helen H.

    2009-01-01

    Obesity and insulin resistance are associated with deposition of triglycerides in tissues other than adipose tissue. Previously, we showed that a missense mutation (I148M) in PNPLA3 (patatin-like phospholipase domain-containing 3 protein) is associated with increased hepatic triglyceride content in humans. Here we examined the effect of the I148M substitution on the enzymatic activity and cellular location of PNPLA3. Structural modeling predicted that the substitution of methionine for isoleu...

  3. Therapeutic Targets of Triglyceride Metabolism as Informed by Human Genetics.

    Bauer, Robert C; Khetarpal, Sumeet A; Hand, Nicholas J; Rader, Daniel J

    2016-04-01

    Human genetics has contributed to the development of multiple drugs to treat hyperlipidemia and coronary artery disease (CAD), most recently including antibodies targeting PCSK9 to reduce LDL cholesterol. Despite these successes, a large burden of CAD remains. Genetic and epidemiological studies have suggested that circulating triglyceride (TG)-rich lipoproteins (TRLs) are a causal risk factor for CAD, presenting an opportunity for novel therapeutic strategies. We discuss recent unbiased human genetics testing, including genome-wide association studies (GWAS) and whole-genome or -exome sequencing, that have identified the lipoprotein lipase (LPL) and hepatic lipogenesis pathways as important mechanisms in the regulation of circulating TRLs. Further strengthening the causal relationship between TRLs and CAD, findings such as these may provide novel targets for much-needed potential therapeutic interventions. PMID:26988439

  4. Domain exchange: characterization of a chimeric lipase of hepatic lipase and lipoprotein lipase.

    Wong, H; Davis, R. C.; Nikazy, J; Seebart, K E; Schotz, M C

    1991-01-01

    Hepatic lipase and lipoprotein lipase hydrolyze fatty acids from triacylglycerols and are critical in the metabolism of circulating lipoproteins. The two lipases are similar in size and amino acid sequence but are distinguished by functional differences in substrate preference and cofactor requirement. Presumably, these distinctions result from structural differences in functional domains. To begin localization of these domains, a chimeric lipase was constructed composed of the N-terminal 329...

  5. Characterization of lipase in reversed micelles formulated by Cibacron Blue F-3GA modified Span 85

    Zhang, Dong Hao; Guo, Zheng; Sun, Yan

    2007-01-01

    reversed micellar technology could increase the apparent activity of enzymes and even yield superactivity for specific enzymes (6). Lipases are ubiquitous enzymes that could find many important applications (7, 8). The natural substrate of lipases is triglyceride, and the majority of lipases are......Sorbitan trioleate (Span 85) modified by Cibacron Blue F-3GA (CB) was prepared and used as an affinity surfactant to formulate a reversed micellar system for Candida rugosa lipase (CRL) solubilization. The system was characterized and evaluated by employing CRL-catalyzed hydrolysis of olive oil as...... a model reaction. The micellar hydrodynamic radius results reflected, to some extent, the redistribution of surfactant and water after enzyme addition, and the correlation between surfactant formulation, water content (W0), micellar size, and enzyme activity. An adequate modification density of CB...

  6. Pathways commonly dysregulated in mouse and human obese adipose tissue: FAT/CD36 modulates differentiation and lipogenesis

    Berger, E.; Héraud, S; Mojallal, A; Lequeux, C; Weiss-Gayet, M; Damour, O.; Géloën, A.

    2015-01-01

    Obesity is linked to adipose tissue hypertrophy (increased adipocyte cell size) and hyperplasia (increased cell number). Comparative analyses of gene datasets allowed us to identify 1426 genes which may represent common adipose phenotype in humans and mice. Among them we identified several adipocyte-specific genes dysregulated in obese adipose tissue, involved in either fatty acid storage (acyl CoA synthase ACSL1, hormone-sensitive lipase LIPE, aquaporin 7 AQP7, perilipin PLIN) or cell adhesi...

  7. Amplification of thermostable lipase genes fragment from thermogenic phase of domestic waste composting process

    Nurhasanah, Nurbaiti, Santi; Madayanti, Fida; Akhmaloka

    2015-09-01

    Lipases are lipolytic enzymes, catalyze the hydrolysis of fatty acid ester bonds of triglycerides to produce free fatty acids and glycerol. The enzyme is widely used in various fields of biotechnological industry. Hence, lipases with unique properties (e.g.thermostable lipase) are still being explored by variation methods. One of the strategy is by using metagenomic approach to amplify the gene directly from environmental sample. This research was focused on amplification of lipase gene fragment directly from the thermogenic phase of domestic waste composting in aerated trenches. We used domestic waste compost from waste treatment at SABUGA, ITB for the sample. Total chromosomal DNA were directly extracted from several stages at thermogenic phase of compost. The DNA was then directly used as a template for amplification of thermostable lipase gene fragments using a set of internal primers namely Flip-1a and Rlip-1a that has been affixed with a GC clamp in reverse primer. The results showed that the primers amplified the gene from four stages of thermogenic phase with the size of lipase gene fragment of approximately 570 base pairs (bp). These results were further used for Denaturing Gradient Gel Electrophoresis (DGGE) analysis to determine diversity of thermostable lipase gene fragments.

  8. Marine Fungal and Bacterial Isolates for Lipase Production: A Comparative Study.

    Patnala, H S; Kabilan, U; Gopalakrishnan, L; Rao, R M D; Kumar, D S

    2016-01-01

    Lipases, belonging to the class of enzymes called hydrolases, can catalyze triglycerides to fatty acids and glycerol. They are produced by microbes of plant and animal origin, and also by marine organisms. As marine microorganisms thrive in extreme conditions, lipases isolated from their origin possess characteristics of extremozymes, retain its activity in extreme conditions and can catalyze few chemical reactions which are impossible otherwise relative to the lipase produced from terrestrial microorganisms. Lipases are useful in many industries like detergent, food, leather, pharmaceutical, diary, etc. Few commercial enzymes have been developed and the use of them in certain industries like dairy, soaps are proved to be beneficial. There are few research papers reporting the production of lipase from marine bacteria and fungi. Lipase production involves two types of fermentation processes-solid-state fermentation (SSF) and submerged fermentation (SmF). Although SmF process is used conventionally, SSF process produces lipase in higher amounts. The production is also influenced by the composition of the medium, physiochemical parameters like temperature, pH, carbon, and nitrogen sources. PMID:27452166

  9. Defective Differentiation of Adipose Precursor Cells from Lipodystrophic Mice Lacking Perilipin 1

    Ying Lyu; Xueying Su; Jingna Deng; Shangxin Liu; Liangqiang Zou; Xiaojing Zhao; Suning Wei; Bin Geng; Guoheng Xu

    2015-01-01

    Perilipin 1 (Plin1) localizes at the surface of lipid droplets to regulate triglyceride storage and hydrolysis in adipocytes. Plin1 defect leads to low adiposity in mice and partial lipodystrophy in human. This study investigated the roles of Plin1 in adipocyte differentiation. Plin1 null (-/-) mice showed plenty of multilocular adipocytes and small unilocular adipocytes in adipose tissue, along with lack of a subpopulation of adipose progenitor cells capable of in vivo adipogenesis and along...

  10. Crystal structure of a triacylglycerol lipase from Penicillium expansum at 1.3 A determined by sulfur SAD

    Bian, Chuanbing; Yuan, Cai; Chen, Liqing; Meehan, Edward J.; Jiang, Longguang; Huang, Zixiang; Lin, Lin; Huang, Mingdong; (UAH); (Fujian); (Chinese Aca. Sci.)

    2010-04-05

    Triacylglycerol lipases (EC 3.1.1.3) are present in many different organisms including animals, plants, and microbes. Lipases catalyze the hydrolysis of long-chain triglycerides into fatty acids and glycerol at the interface between the water insoluble substrate and the aqueous phase. Lipases can also catalyze the reverse esterification reaction to form glycerides under certain conditions. Lipases of microbial origin are of considerable commercial interest for wide variety of biotechnological applications in industries, including detergent, food, cosmetic, pharmaceutical, fine chemicals, and biodiesel. Nowadays, microbial lipases have become one of the most important industrial enzymes. PEL (Penicillium expansum lipase) is a fungal lipase from Penicillium expansum strain PF898 isolated from Chinese soil that has been subjected to several generations of mutagenesis to increase its enzymatic activity. PEL belongs to the triacylglycerol lipases family, and its catalytic characteristics have been studied. The enzyme has been used in Chinese laundry detergent industry for several years (http://www.leveking.com). However, the poor thermal stability of the enzyme limits its application. To further study and improve this enzyme, PEL was cloned and sequenced. Furthermore, it was overexpressed in Pichia pastoris. PEL contains GHSLG sequence, which is the lipase consensus sequence Gly-X1-Ser-X2-Gly, but has a low amino acid sequence identities to other lipases. The most similar lipases are Rhizomucor miehei (PML) and Rhizopus niveus (PNL) with a 21% and 20% sequence identities to PEL, respectively. Interestingly, the similarity of PEL with the known esterases is somewhat higher with 24% sequence identity to feruloyl esterase A. Here, we report the 1.3 {angstrom} resolution crystal structure of PEL determined by sulfur SAD phasing. This structure not only presents a new lipase structure at high resolution, but also provides a structural platform to analyze the published

  11. Lipase biofilm deposited by Matrix Assisted Pulsed Laser Evaporation technique

    Aronne, Antonio [Department of Chemical Engineering, Materials and Industrial Production, University of Naples “Federico II”, Napoli (Italy); Bloisi, Francesco, E-mail: bloisi@na.infn.it [SPIN – CNR, Naples (Italy); Department of Physics, University of Naples “Federico II”, Napoli (Italy); Calabria, Raffaela; Califano, Valeria [Istituto Motori – CNR, Naples (Italy); Depero, Laura E. [Department of Mechanical and Industrial Engineering, University of Brescia, Brescia (Italy); Fanelli, Esther [Department of Chemical Engineering, Materials and Industrial Production, University of Naples “Federico II”, Napoli (Italy); Federici, Stefania [Department of Mechanical and Industrial Engineering, University of Brescia, Brescia (Italy); Massoli, Patrizio [Istituto Motori – CNR, Naples (Italy); Vicari, Luciano R.M. [SPIN – CNR, Naples (Italy); Department of Physics, University of Naples “Federico II”, Napoli (Italy)

    2015-05-01

    Highlights: • A lipase film was deposited with Matrix Assisted Pulsed Laser Evaporation technique. • FTIR spectra show that laser irradiation do not damage lipase molecule. • Laser fluence controls the characteristics of complex structure generated by MAPLE. - Abstract: Lipase is an enzyme that finds application in biodiesel production and for detection of esters and triglycerides in biosensors. Matrix Assisted Pulsed Laser Evaporation (MAPLE), a technique derived from Pulsed Laser Deposition (PLD) for deposition of undamaged biomolecules or polymers, is characterized by the use of a frozen target obtained from a solution/suspension of the guest material (to be deposited) in a volatile matrix (solvent). The presence of the solvent avoids or at least reduces the potential damage of guest molecules by laser radiation but only the guest material reaches the substrate in an essentially solvent-free deposition. MAPLE can be used for enzymes immobilization, essential for industrial application, allowing the development of continuous processes, an easier separation of products, the reuse of the catalyst and, in some cases, enhancing enzyme properties (pH, temperature stability, etc.) and catalytic activity in non-aqueous media. Here we show that MAPLE technique can be used to deposit undamaged lipase and that the complex structure (due to droplets generated during extraction from target) of the deposited material can be controlled by changing the laser beam fluence.

  12. Lipase biofilm deposited by Matrix Assisted Pulsed Laser Evaporation technique

    Highlights: • A lipase film was deposited with Matrix Assisted Pulsed Laser Evaporation technique. • FTIR spectra show that laser irradiation do not damage lipase molecule. • Laser fluence controls the characteristics of complex structure generated by MAPLE. - Abstract: Lipase is an enzyme that finds application in biodiesel production and for detection of esters and triglycerides in biosensors. Matrix Assisted Pulsed Laser Evaporation (MAPLE), a technique derived from Pulsed Laser Deposition (PLD) for deposition of undamaged biomolecules or polymers, is characterized by the use of a frozen target obtained from a solution/suspension of the guest material (to be deposited) in a volatile matrix (solvent). The presence of the solvent avoids or at least reduces the potential damage of guest molecules by laser radiation but only the guest material reaches the substrate in an essentially solvent-free deposition. MAPLE can be used for enzymes immobilization, essential for industrial application, allowing the development of continuous processes, an easier separation of products, the reuse of the catalyst and, in some cases, enhancing enzyme properties (pH, temperature stability, etc.) and catalytic activity in non-aqueous media. Here we show that MAPLE technique can be used to deposit undamaged lipase and that the complex structure (due to droplets generated during extraction from target) of the deposited material can be controlled by changing the laser beam fluence

  13. Covalent immobilization of Pseudomonas cepacia lipase on semiconducting materials

    Fernandez, Renny Edwin [Microelectronics and MEMS Laboratory, Department of Electrical Engineering, Indian Institute of Technology Madras, Chennai (India)], E-mail: rennyedwin@gmail.com; Bhattacharya, Enakshi [Microelectronics and MEMS Laboratory, Department of Electrical Engineering, Indian Institute of Technology Madras, Chennai (India)], E-mail: enakshi@ee.iitm.ac.in; Chadha, Anju [Department of Biotechnology, National Centre for Catalysis Research, Indian Institute of Technology Madras, Chennai (India)], E-mail: anjuc@iitm.ac.in

    2008-05-30

    Lipase from Pseudomonas cepacia was covalently immobilized on crystalline silicon, porous silicon and silicon nitride surfaces. The various stages of immobilization were characterized using FTIR (Fourier transform infrared) spectroscopy. The surface topography of the enzyme immobilized surfaces was investigated using scanning electron microscopy (SEM). The quantity of the immobilized active enzyme was estimated by the para-nitrophenyl palmitate (pNPP) assay. The immobilized lipase was used for triglyceride hydrolysis and the acid produced was detected by a pH sensitive silicon nitride surface as a shift in the C-V (capacitance-voltage) characteristics of an electrolyte-insulator-semiconductor capacitor (EISCAP) thus validating the immobilization method for use as a biosensor.

  14. Covalent immobilization of Pseudomonas cepacia lipase on semiconducting materials

    Lipase from Pseudomonas cepacia was covalently immobilized on crystalline silicon, porous silicon and silicon nitride surfaces. The various stages of immobilization were characterized using FTIR (Fourier transform infrared) spectroscopy. The surface topography of the enzyme immobilized surfaces was investigated using scanning electron microscopy (SEM). The quantity of the immobilized active enzyme was estimated by the para-nitrophenyl palmitate (pNPP) assay. The immobilized lipase was used for triglyceride hydrolysis and the acid produced was detected by a pH sensitive silicon nitride surface as a shift in the C-V (capacitance-voltage) characteristics of an electrolyte-insulator-semiconductor capacitor (EISCAP) thus validating the immobilization method for use as a biosensor

  15. Fatty Acid Signaling: The New Function of Intracellular Lipases

    Zuzana Papackova

    2015-02-01

    Full Text Available Until recently, intracellular triacylglycerols (TAG stored in the form of cytoplasmic lipid droplets have been considered to be only passive “energy conserves”. Nevertheless, degradation of TAG gives rise to a pleiotropic spectrum of bioactive intermediates, which may function as potent co-factors of transcription factors or enzymes and contribute to the regulation of numerous cellular processes. From this point of view, the process of lipolysis not only provides energy-rich equivalents but also acquires a new regulatory function. In this review, we will concentrate on the role that fatty acids liberated from intracellular TAG stores play as signaling molecules. The first part provides an overview of the transcription factors, which are regulated by fatty acids derived from intracellular stores. The second part is devoted to the role of fatty acid signaling in different organs/tissues. The specific contribution of free fatty acids released by particular lipases, hormone-sensitive lipase, adipose triacylglycerol lipase and lysosomal lipase will also be discussed.

  16. Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed

    Makoveichuk, Elena; Sukonina, Valentina; Kroupa, Olessia [Department of Medical Biosciences, Physiological Chemistry Umea University, SE-901 87 Umea (Sweden); Thulin, Petra; Ehrenborg, Ewa [Atherosclerosis Research Unit, Department of Medicine, Karolinska Institutet, SE-171 76 Stockholm (Sweden); Olivecrona, Thomas [Department of Medical Biosciences, Physiological Chemistry Umea University, SE-901 87 Umea (Sweden); Olivecrona, Gunilla, E-mail: Gunilla.Olivecrona@medbio.umu.se [Department of Medical Biosciences, Physiological Chemistry Umea University, SE-901 87 Umea (Sweden)

    2012-08-24

    Highlights: Black-Right-Pointing-Pointer Lipoprotein lipase (LPL) activity is controlled by ANGPTL4 in THP-1 macrophages. Black-Right-Pointing-Pointer Both LPL and ANGPTL4 bind to THP-1 macrophages in a heparin-releasable fashion. Black-Right-Pointing-Pointer Only monomers of ANGPTL4 are present within THP-1 macrophages. Black-Right-Pointing-Pointer Covalent oligomers of ANGPTL4 appear on cell surface and in medium. Black-Right-Pointing-Pointer Inactivation of LPL coincide with ANGPTL4 oligomer formation on cell surfaces. -- Abstract: Lipoprotein lipase (LPL) hydrolyzes triglycerides in plasma lipoproteins causing release of fatty acids for metabolic purposes in muscles and adipose tissue. LPL in macrophages in the artery wall may, however, promote foam cell formation and atherosclerosis. Angiopoietin-like protein (ANGPTL) 4 inactivates LPL and ANGPTL4 expression is controlled by peroxisome proliferator-activated receptors (PPAR). The mechanisms for inactivation of LPL by ANGPTL4 was studied in THP-1 macrophages where active LPL is associated with cell surfaces in a heparin-releasable form, while LPL in the culture medium is mostly inactive. The PPAR{delta} agonist GW501516 had no effect on LPL mRNA, but increased ANGPTL4 mRNA and caused a marked reduction of the heparin-releasable LPL activity concomitantly with accumulation of inactive, monomeric LPL in the medium. Intracellular ANGPTL4 was monomeric, while dimers and tetramers of ANGPTL4 were present in the heparin-releasable fraction and medium. GW501516 caused an increase in the amount of ANGPTL4 oligomers on the cell surface that paralleled the decrease in LPL activity. Actinomycin D blocked the effects of GW501516 on ANGPTL4 oligomer formation and prevented the inactivation of LPL. Antibodies against ANGPTL4 interfered with the inactivation of LPL. We conclude that inactivation of LPL in THP-1 macrophages primarily occurs on the cell surface where oligomers of ANGPTL4 are formed.

  17. Inactivation of lipoprotein lipase occurs on the surface of THP-1 macrophages where oligomers of angiopoietin-like protein 4 are formed

    Highlights: ► Lipoprotein lipase (LPL) activity is controlled by ANGPTL4 in THP-1 macrophages. ► Both LPL and ANGPTL4 bind to THP-1 macrophages in a heparin-releasable fashion. ► Only monomers of ANGPTL4 are present within THP-1 macrophages. ► Covalent oligomers of ANGPTL4 appear on cell surface and in medium. ► Inactivation of LPL coincide with ANGPTL4 oligomer formation on cell surfaces. -- Abstract: Lipoprotein lipase (LPL) hydrolyzes triglycerides in plasma lipoproteins causing release of fatty acids for metabolic purposes in muscles and adipose tissue. LPL in macrophages in the artery wall may, however, promote foam cell formation and atherosclerosis. Angiopoietin-like protein (ANGPTL) 4 inactivates LPL and ANGPTL4 expression is controlled by peroxisome proliferator-activated receptors (PPAR). The mechanisms for inactivation of LPL by ANGPTL4 was studied in THP-1 macrophages where active LPL is associated with cell surfaces in a heparin-releasable form, while LPL in the culture medium is mostly inactive. The PPARδ agonist GW501516 had no effect on LPL mRNA, but increased ANGPTL4 mRNA and caused a marked reduction of the heparin-releasable LPL activity concomitantly with accumulation of inactive, monomeric LPL in the medium. Intracellular ANGPTL4 was monomeric, while dimers and tetramers of ANGPTL4 were present in the heparin-releasable fraction and medium. GW501516 caused an increase in the amount of ANGPTL4 oligomers on the cell surface that paralleled the decrease in LPL activity. Actinomycin D blocked the effects of GW501516 on ANGPTL4 oligomer formation and prevented the inactivation of LPL. Antibodies against ANGPTL4 interfered with the inactivation of LPL. We conclude that inactivation of LPL in THP-1 macrophages primarily occurs on the cell surface where oligomers of ANGPTL4 are formed.

  18. Catalytically inactive lipoprotein lipase expression in muscle of transgenic mice increases very low density lipoprotein uptake: Direct evidence that lipoprotein lipase bridging occurs in vivo

    Merkel, Martin; Kako, Yuko; Radner, Herbert; Cho, Irene S.; Ramasamy, Ravi; Brunzell, John D.; Goldberg, Ira J.; Breslow, Jan L.

    1998-01-01

    Lipoprotein lipase (LPL) is the central enzyme in plasma triglyceride hydrolysis. In vitro studies have shown that LPL also can enhance lipoprotein uptake into cells via pathways that are independent of catalytic activity but require LPL as a molecular bridge between lipoproteins and proteoglycans or receptors. To investigate whether this bridging function occurs in vivo, two transgenic mouse lines were established expressing a muscle creatine kinase promoter-driven human LPL (hLPL) minigene ...

  19. Depot-specific differences in perilipin and hormone-sensitive lipase expression in lean and obese

    Beylot Michel

    2009-12-01

    Full Text Available Abstract Background Mainly dependent on hormone-sensitive lipase, lipolysis is differently impaired between fat depots in human obesity. Perilipin A expression is a critical element in adipocyte lipolysis. The present study aimed at comparing expression and subcellular distribution of perilipin and hormone-sensitive lipase in two abdominal adipose tissues of lean and obese women. We examined whether regional differences in perilipin expression contribute to impaired lipolytic rates. Methods Abdominal subcutaneous and omental adipose tissues were obtained from six lean and ten obese women. We measured total protein content and relative distribution of hormone-sensitive lipase and perilipin proteins between lipid and non-lipid fractions in tissue homogenates. Hormone-sensitive lipase and perilipin mRNA levels, adipocyte size, basal (non-stimulated and noradrenaline-stimulated lipolysis in isolated adipocytes were determined. Results Adipocytes were significantly larger in the obese versus the lean women and in subcutaneous versus omental fat. Expressed as a function of cell number, basal lipolysis and noradrenaline responsiveness were higher in subcutaneous versus omental adipocytes from the obese women (P Conclusion In both fat depots, a reduced perilipin protein expression was observed in women obesity. Perilipin protein level may contribute to differences in basal lipolysis and in adipocyte size between fat depots and may regulate lipid accumulation in adipocytes. Differences in hormone-sensitive lipase subcellular distribution were reported between fat depots in the obese women.

  20. Inhibitors of pancreatic lipase

    Lunagariya, Nitin A.; Patel, Neeraj K.; Jagtap, Sneha C.; Bhutani, Kamlesh K.

    2014-01-01

    Obesity is a disorder of lipid metabolism and continues to be a global problem, ranking fifth for deaths worldwide. It also leads to diabetes, cardiovascular disorders, musculoskeletal disorders and some types of cancer. Obesity is regarded as the output of a long-term imbalance between energy intake and energy expenditure. Digestion and absorption of dietary lipids by pancreatic lipase, a major source of excess calorie intake, can be targeted for development of anti-obesity agents. Being the...

  1. The fatty liver dystrophy (fld) mutation: Developmentally related alterations in hepatic triglyceride metabolism and protein expression

    Reue, K.; Rehnmark, S.; Cohen, R.D.; Leete, T.H.; Doolittle, M.H. [West Los Angeles VA Medical Center, CA (United States). Lipid Research Lab.]|[Univ. of California, Los Angeles, CA (United States). Dept. of Medicine; Giometti, C.S.; Mishler, K. [Argonne National Lab., IL (United States); Slavin, B.G. [Univ. of Southern California, Los Angeles, CA (United States)

    1997-07-01

    Fatty liver dystrophy (fld) is an autosomal recessive mutation in mice characterized by hypertriglyceridemia and development of a fatty liver in the early neonatal period. Also associated with the fld phenotype is a tissue-specific deficiency in the expression of lipoprotein lipase and hepatic lipase, as well as elevations in hepatic apolipoprotein A-IV and apolipoprotein C-II mRNA levels. Although these lipid abnormalities resolve at the age of weaning, adult mutant mice exhibit a peripheral neuropathy associated with abnormal myelin formation. The fatty liver in fld/fld neonates is characterized by the accumulation of large triglyceride droplets within the parenchymal cells, and these droplets persist within isolated hepatocytes maintained in culture for several days. To identify the metabolic defect that leads to lipid accumulation, the authors investigated several aspects of cellular triglyceride metabolism. The mutant mice exhibited normal activity of acid triacylglycerol lipase, an enzyme thought to be responsible for hydrolysis of dietary triglycerides in the liver. Metabolic labeling studies performed with oleic acid revealed that free fatty acids accumulate in the liver of 3 day old fld/fld mice, but not in adults. This accumulation in liver was mirrored by elevated free fatty acid levels in plasma of fld/fld neonates, with levels highest in very young mice and returning to normal by the age of one month. Quantitation of fatty acid oxidation in cells isolated from fld/fld neonates revealed that oxidation rate is reduced 60% in hepatocytes and 40% in fibroblasts; hepatocytes from adult fld/fld mice exhibited an oxidation rate similar to those from wild-type mice.

  2. High-Level Expression of Pro-Form Lipase from Rhizopus oryzae in Pichia pastoris and Its Purification and Characterization

    Jian-Rong Wang

    2013-12-01

    Full Text Available A gene encoding Rhizopus oryzae lipase containing prosequence (ProROL was cloned into the pPICZαA and electrotransformed into the Pichia pastoris X-33 strain. The lipase was functionally expressed and secreted in Pichia pastoris with a molecular weight of 35 kDa. The maximum lipase activity of recombinant lipase (rProROL was 21,000 U/mL, which was obtained in a fed-batch cultivation after 168 h induction with methanol in a 50-L bioreactor. After fermentation, the supernatant was concentrated by ultrafiltration with a 10 kDa cut off membrane and purified with ion exchange chromatography using SP Sepharose Fast Flow chromatography. The optimum pH and temperature of the rProROL were pH 9.0 and 40 °C, respectively. The lipase was stable from pH 4.0 to 9.0 and from 25 to 55 °C. The enzyme activity was enhanced by Ca2+ and inhibited by Hg2+ and Ag+. The lipase showed high activity toward triglyceride-Tripalmitin (C16:0 and triglyceride-Trilaurin (C12:0.

  3. Variation in the ovine hormone-sensitive lipase gene (HSL) and its association with growth and carcass traits in New Zealand Suffolk sheep.

    Yang, Guo; Forrest, Rachel; Zhou, Huitong; Hickford, Jonathan

    2014-01-01

    The hormone-sensitive lipase (HSL) plays an important role in the regulation of lipolysis in adipose tissues, by catalysing a rate-limiting step in triglyceride hydrolysis. Variation within the human HSL gene (HSL) has been associated with an increased risk of obesity. In this study, variation within three regions (exon 3-4, exon 5-6 and exon 9) of ovine HSL was investigated in 538 Suffolk lambs bred from 13 independent sires using PCR-SSCP. Four sequence variants of intron 5 (designated A-D) and two variants of exon 9 (designated a and b) of ovine HSL were detected. No variation was found in exon 3-4 of the gene. The associations of the variation within ovine HSL with post-weaning growth and carcass traits including eye muscle depth (EMD), eye muscle width (EMW) and fat depth above the eye muscle (FDM) were assessed in 262 of the above 538 lambs using general linear mixed-effects models. In the single variant models, the presence of intron 5 A in a lamb's genotype was associated with reduced EMD (P = 0.036) and EMW (P = 0.018), whereas the presence of intron 5 C was associated with increased EMD (P growth, or between HSL exon 9 variants, post-weaning growth or carcass traits, were found. PMID:24443229

  4. X-ray structure of Candida antarctica lipase A shows a novel lid structure and a likely mode of interfacial activation

    Ericsson, Daniel J.; Kasrayan, Alex; Johansson, Patrik; Bergfors, Terese; Sandström, Anders G.; Bäckvall, Jan-Erling; Mowbray, Sherry L.

    2008-01-01

    In nature, lipases (EC 3.1.1.3) catalyze the hydrolysis of triglycerides to form glycerol and fatty acids. Under the appropriate conditions, the reaction is reversible, and so biotechnological applications commonly make use of their capacity for esterification as well as for hydrolysis of a wide variety of compounds. In the present paper, we report the X-ray structure of lipase A from Candida antarctica, solved by single isomorphous replacement with anomalous scattering, and refined to 2.2-A ...

  5. Angiopoietin-like protein 4 inhibition of lipoprotein lipase: evidence for reversible complex formation.

    Lafferty, Michael J; Bradford, Kira C; Erie, Dorothy A; Neher, Saskia B

    2013-10-01

    Elevated triglycerides are associated with an increased risk of cardiovascular disease, and lipoprotein lipase (LPL) is the rate-limiting enzyme for the hydrolysis of triglycerides from circulating lipoproteins. The N-terminal domain of angiopoietin-like protein 4 (ANGPTL4) inhibits LPL activity. ANGPTL4 was previously described as an unfolding molecular chaperone of LPL that catalytically converts active LPL dimers into inactive monomers. Our studies show that ANGPTL4 is more accurately described as a reversible, noncompetitive inhibitor of LPL. We find that inhibited LPL is in a complex with ANGPTL4, and upon dissociation, LPL regains lipase activity. Furthermore, we have generated a variant of ANGPTL4 that is dependent on divalent cations for its ability to inhibit LPL. We show that LPL inactivation by this regulatable variant of ANGPTL4 is fully reversible after treatment with a chelator. PMID:23960078

  6. Aspects of plasma triglyceride metabolism in children

    P.P. Forget

    1975-01-01

    textabstractThis thesis aimed at investigating some aspects of plasma triglyceride metabolism in children. In the introduction general aspects of plasma triglyceride metabolism are presented. Chapter 1 reviews recent litterature data on the intravenous fat tolerance test and on plasma postheparin li

  7. Serum triglycerides and risk of cardiovascular disease.

    Boullart, I.; Graaf, J. de; Stalenhoef, A.F.H.

    2012-01-01

    Dyslipidemia, especially elevated serum levels of cholesterol, is causally related to cardiovascular disease. The specific role of triglycerides has long been controversial. In this article we discuss the role of serum triglycerides in relation to the risk of cardiovascular disease. First, the (path

  8. Mice subjected to aP2-Cre mediated ablation of microsomal triglyceride transfer protein are resistant to high fat diet induced obesity

    Bakillah, Ahmed; Hussain, M. Mahmood

    2016-01-01

    Background Microsomal triglyceride transfer protein (MTP) is essential for the assembly of lipoproteins. MTP has been shown on the surface of lipid droplets of adipocytes; however its function in adipose tissue is not well defined. We hypothesized that MTP may play critical role in adipose lipid droplet formation and expansion. Methods Plasmids mediated overexpression and siRNA mediated knockdown of Mttp gene were performed in 3T3-L1 pre-adipocytes to evaluate the effects of MTP on cell diffe...

  9. Pancreatic carboxyl ester lipase: a circulating enzyme that modifies normal and oxidized lipoproteins in vitro.

    Shamir, R; W.J. Johnson; Morlock-Fitzpatrick, K; Zolfaghari, R; Li, L.; E. Mas; Lombardo, D; Morel, D W; Fisher, E A

    1996-01-01

    Pancreatic carboxyl ester lipase (CEL) hydrolyzes cholesteryl esters (CE), triglycerides (TG), and lysophospholipids, with CE and TG hydrolysis stimulated by cholate. Originally thought to be confined to the gastrointestinal system, CEL has been reported in the plasma of humans and other mammals, implying its potential in vivo to modify lipids associated with LDL, HDL (CE, TG), and oxidized LDL (lysophosphatidylcholine, lysoPC). We measured the concentration of CEL in human plasma as 1.2+/-0....

  10. Chylous ascites secondary to hyperlipidemic pancreatitis with normal serum amylase and lipase

    Khan, Fahmi Yousef; Matar, Issa

    2007-01-01

    A 54-year old man with a family history of hyperlipidemia was admitted with a 12 h history of severe generalized abdominal pain associated with nausea, vomiting and abdominal distension. Examination of the abdomen revealed tenderness in the periumblical area with shifting dullness. Serum pancreatic amylase was 29 IU/L and lipase 44 IU/L, triglyceride 36.28 mmol/L. Ultrasound showed ascites. CT of the abdomen with contrast showed inflammatory changes surrounding the pancreas consistent with ac...

  11. The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

    Malloy Mary J; Pullinger Clive R; Kulkarni Medha V; Wung Shu-Fen; Kane John P; Aouizerat Bradley E

    2006-01-01

    Abstract Background Lipoprotein Lipase (LPL), a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG) from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH). Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles rema...

  12. The common biological basis for common complex diseases: evidence from lipoprotein lipase gene

    Xie, Cui; Wang, Zeng Chan; Liu, Xiao Feng; Yang, Mao Sheng

    2009-01-01

    The lipoprotein lipase (LPL) gene encodes a rate-limiting enzyme protein that has a key role in the hydrolysis of triglycerides. Hypertriglyceridemia, one widely prevalent syndrome of LPL deficiency and dysfunction, may be a risk factor in the development of dyslipidemia, type II diabetes (T2D), essential hypertension (EH), coronary heart disease (CHD) and Alzheimer's disease (AD). Findings from earlier studies indicate that LPL may have a role in the pathology of these diseases and therefore...

  13. Lipoprotein lipase increases low density lipoprotein retention by subendothelial cell matrix.

    Saxena, U; Klein, M. G.; Vanni, T M; Goldberg, I J

    1992-01-01

    Lipoprotein lipase (LPL), the rate-limiting enzyme for hydrolysis of plasma lipoprotein triglycerides, is a normal constituent of the arterial wall. We explored whether LPL affects (a) lipoprotein transport across bovine aortic endothelial cells or (b) lipoprotein binding to subendothelial cell matrix (retention). When bovine milk LPL was added to endothelial cell monolayers before addition of 125I-labeled LDL, LDL transport across the monolayers was unchanged; but, at all concentrations of L...

  14. Penicillium restrictum lipases : A comparative study and characterization of enzymes with different degrees of purity

    JESUS M.F.C.P.

    1999-01-01

    Full Text Available Penicillium restrictum was identified as a promising strain for lipase production due to enzyme production yield and thermal stability of the enzyme. This work presents results of lipase purification and enzyme stability versus pH. Ultrafiltration and precipitation with ammonium sulphate were used as initial purification steps. The partially purified enzyme preparation showed an increase in stability as pH increased. The crude enzymatic preparation was assayed with different oils and tributirin and showed a major catalytic activity for triglycerides of medium/long-chain fatty acids. Further purification steps were conducted on an analytical scale. The initial attempt to use gel filtration was abandoned as lipase lost its stability after this chromatographic procedure. The fast ion-exchange chromatography was performed on a Mono Q column, and two peaks with lipolytic activity were isolated and analysed by electrophoresis.

  15. Orientating lipase molecules through surface chemical control for enhanced activity: A QCM-D and ToF-SIMS investigation.

    Joyce, Paul; Kempson, Ivan; Prestidge, Clive A

    2016-06-01

    Bio-active materials consisting of lipase encapsulated within porous silica particles were engineered to control the adsorption kinetics and molecular orientation of lipase, which play critical roles in the digestion kinetics of triglycerides. The adsorption kinetics of Candida antartica lipase A (CalA) was monitored using quartz crystal microbalance with dissipation (QCM-D) and controlled by altering the hydrophobicity of a silica binding support. The extent of adsorption was 2-fold greater when CalA was adsorbed onto hydrophobic silica compared to hydrophilic silica. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) fragmentation patterns, in conjunction with multivariate statistics, demonstrated enhanced exposure of the lipase's catalytic domain, specifically the histidine group responsible for activity, when CalA was adsorbed on hydrophilic silica. Consequently, lipid digestion kinetics were enhanced when CalA was loaded in hydrophilic porous silica particles, i.e., a 2-fold increase in the pseudo-first-order rate constant for digestion when compared to free lipase. In contrast, digestion kinetics were inhibited when CalA was hosted in hydrophobic porous silica, i.e., a 5-fold decrease in pseudo-first-order rate constant for digestion when compared to free lipase. These findings provide valuable insights into the mechanism of lipase action which can be exploited to develop smarter food and drug delivery systems consisting of porous lipid-based materials. PMID:26954083

  16. Lipase Maturation Factor 1: a lipase chaperone involved in lipid metabolism

    Péterfy, Miklós

    2011-01-01

    Mutations in lipase maturation factor 1 (LMF1) are associated with severe hypertriglyceridemia in mice and human subjects. The underlying cause is impaired lipid clearance due to lipase deficiency. LMF1 is a chaperone of the endoplasmic reticulum (ER) and it is critically required for the post-translational activation of three vascular lipases: lipoprotein lipase (LPL), hepatic lipase (HL) and endothelial lipase (EL). As LMF1 is only required for the maturation of homodimeric, but not monomer...

  17. Physical inactivity amplifies the sensitivity of skeletal muscle to the lipid-induced downregulation of lipoprotein lipase activity.

    Zderic, Theodore W; Hamilton, Marc T

    2006-01-01

    Physical inactivity is a risk factor for lipoprotein disorders and the metabolic syndrome. Physical inactivity has a powerful effect on suppressing lipoprotein lipase (LPL) activity in skeletal muscle, the rate-limiting enzyme for hydrolysis of triglyceride (TG)-rich lipoproteins. We tested the ability of several compounds to prevent the decrease in LPL. The present study minimized standing and ordinary light nonexercise movements in rats to compare the effects of inactivity and nonexercise activity thermogenesis (NEAT) on LPL activity. The key new insight was that the typically quick decrease in LPL activity of oxidative muscle caused by physical inactivity was prevented by nicotinic acid (NA), whereas inhibitors of TNF-alpha, inducible nitric oxide synthase, and NF-kappaB had no such effect. NA was administered at a dose known to acutely impede the appearance of plasma TG from the liver and free fatty acids from adipose tissue, and it was effective at intentionally lowering plasma lipid concentrations to the same level in active and inactive groups. As measured from heparin-releasable LPL activity, LPL in the microvasculature of the most oxidative muscles was approximately 90% lower in the inactive group compared with controls, and this suppression was completely blocked by NA. In contrast to inactivity, NA did not raise muscle LPL in ambulatory controls, whereas a large exogenous fat delivery did decrease LPL activity. In vitro control studies revealed that NA did not have a direct effect on skeletal muscle LPL activity. In conclusion, physical inactivity amplifies the ability of plasma lipids to suppress muscle LPL activity. The light ambulatory contractions responsible for NEAT are sufficient for mitigating these deleterious effects. PMID:16195388

  18. Abnormal Patterns of Lipoprotein Lipase Release into the Plasma in GPIHBP1-deficient Mice*

    Weinstein, Michael M.; Yin, Liya; Beigneux, Anne P.; Davies, Brandon S. J.; Gin, Peter; Estrada, Kristine; Melford, Kristan; Bishop, Joseph R.; Esko, Jeffrey D.; Dallinga-Thie, Geesje M.; Fong, Loren G.; Bensadoun, André; Young, Stephen G.

    2008-01-01

    GPIHBP1-deficient mice (Gpihbp1–/–) exhibit severe chylomicronemia. GPIHBP1 is located within capillaries of muscle and adipose tissue, and expression of GPIHBP1 in Chinese hamster ovary cells confers upon those cells the ability to bind lipoprotein lipase (LPL). However, there has been absolutely no evidence that GPIHBP1 actually interacts with LPL in vivo. Heparin is known to release LPL from its in vivo binding sites, allowing it to enter the plasma. After an injection ...

  19. Biodiesel production with immobilized lipase: A review.

    Tan, Tianwei; Lu, Jike; Nie, Kaili; Deng, Li; Wang, Fang

    2010-01-01

    Fatty acid alkyl esters, also called biodiesel, are environmentally friendly and show great potential as an alternative liquid fuel. Biodiesel is produced by transesterification of oils or fats with chemical catalysts or lipase. Immobilized lipase as the biocatalyst draws high attention because that process is "greener". This article reviews the current status of biodiesel production with immobilized lipase, including various lipases, immobilization methods, various feedstocks, lipase inactivation caused by short chain alcohols and large scale industrialization. Adsorption is still the most widely employed method for lipase immobilization. There are two kinds of lipase used most frequently especially for large scale industrialization. One is Candida antartica lipase immobilized on acrylic resin, and the other is Candida sp. 99-125 lipase immobilized on inexpensive textile membranes. However, to further reduce the cost of biodiesel production, new immobilization techniques with higher activity and stability still need to be explored. PMID:20580809

  20. Lipase - Catalyzed glycerolysis of sunflower oil to produce partial glycerides.

    Zaher, F. A.; Aly, Saadia M.; El-Kinawy, O. S.

    1998-01-01

    Partial glycerides were prepared by glycerolysis of sunflower oil in presence of lipase enzyme as catalyst. Six lipases of different origins were used and compared for their catalytic activity. These include Chromobacterium lipase, pancreatic lipase, Rhizopus arrhizus lipase, lyophilized lipase (plant lipase) in addition to two lipase preparations derived from Rhizopus japonicas; Lilipase A-10 and Lilipase B-2. Chromobacterium&...

  1. Regulation of microsomal triglyceride transfer protein

    Hussain, M. Mahmood; Nijstad, Niels; Franceschini, Lisa

    2011-01-01

    Microsomal triglyceride transfer protein (MTP) facilitates the transport of dietary and endogenous fat by the intestine and liver by assisting in the assembly and secretion of triglyceride-rich apolipoprotein B-containing lipoproteins. Higher concentrations of apolipoprotein B lipoproteins predispose individuals to various cardiovascular and metabolic diseases such as atherosclerosis, diabetes, obesity and the metabolic syndrome. These can potentially be avoided by reducing MTP activity. In t...

  2. Adipose tissue fibrosis

    Buechler, Christa; Krautbauer, Sabrina; Eisinger, Kristina

    2015-01-01

    The increasing prevalence of obesity causes a major interest in white adipose tissue biology. Adipose tissue cells are surrounded by extracellular matrix proteins whose composition and remodeling is of crucial importance for cell function. The expansion of adipose tissue in obesity is linked to an inappropriate supply with oxygen and hypoxia development. Subsequent activation of hypoxia inducible factor 1 (HIF-1) inhibits preadipocyte differentiation and initiates adipose tissue fibrosis. The...

  3. Dynamics of human adipose lipid turnover in health and metabolic disease

    Arner, Peter; Bernard, Samuel; Salehpour, Mehran; Possnert, Göran; Liebl, Jakob; Steier, Peter; Buchholz, Bruce A.; Eriksson, Mats; Arner, Erik; Hauner, Hans; Skurk, Thomas; Rydén, Mikael; Frayn, Keith N.; Spalding, Kirsty L.

    2011-01-01

    Adipose tissue mass is determined by the storage and removal of triglycerides in adipocytes. Little is known, however, about adipose lipid turnover in humans in health and pathology. To study this in vivo, lipid age was determined by measuring nuclear bomb test-derived 14C in adipocyte lipids. We report that during the average ten year life span of human adipocytes, triglycerides are renewed six times. Lipid age is independent of adipocyte size, is very stable across a wide range of adult age...

  4. Production of Truncated Candida antarctica Lipase B Gene Using Automated PCR Gene Assembly Protocol and Expression in Yeast for use in Ethanol and Biodiesel Production.

    An improved column-based process for production of biodiesel was developed using a column containing a strongly basic anion-exchange resin in sequence with a column containing a resin to which a lipase biocatalyst is bound. Currently most biodiesel is produced by transesterification of triglyceride...

  5. The acidic domain of the endothelial membrane protein GPIHBP1 stabilizes lipoprotein lipase activity by preventing unfolding of its catalytic domain

    Mysling, Simon; Kristensen, Kristian Kølby; Larsson, Mikael; Beigneux, Anne P; Gårdsvoll, Henrik; Loren, Fong G; Bensadouen, André; Jørgensen, Thomas Jd; Young, Stephen G; Ploug, Michael

    2016-01-01

    GPIHBP1 is a glycolipid-anchored membrane protein of capillary endothelial cells that binds lipoprotein lipase (LPL) within the interstitial space and shuttles it to the capillary lumen. The LPL•GPIHBP1 complex is responsible for margination of triglyceride-rich lipoproteins along capillaries and...

  6. MOLECULAR MODELING AND DOCKING STUDIES OF COLD ACTIVE LIPASE FROM Pseudomonas fluorescens

    G. N. Gupta

    2015-03-01

    Full Text Available Molecular Modeling is essential tool in the drug design process describes the generation, manipulation or representation of 3D structures of the molecules and associated physico-chemical properties while docking predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. A cold active lipase producing potential psychrophilic bacteria (GN was isolated and identified by 16S rRNA molecular studies as Pseudomonas vancouverensis. Lipase gene from closely related species P. fluorescens was investigated for their functional role and in silico characterization using molecular modeling and docking studies. A 3D structure of lipase gene was generated with SWISS-MODEL and Discovery Studio 3.0. The stereochemistry of the constructed model of cold active lipase was subjected to energy minimization and the stereo-chemical quality of the predicted structure was assessed. The superimposition of the template (PDBID: 2Z8X with predicted structure showed that weighted root mean square deviation of Cα trace between the template and the final refined model was 0.2 Å with a significant Zscore of 8.2 and sequence identity was 80.5%. Three ligands P-Nitrophenol, Acetate ion and Diethyl phosphonate were taken for docking calculation with generated structure. They were interacting on the functional motifs of predicted model. It has been observed that Leu26, Tyr29, Asn31, Asp33, Pro315 and Thr316 residues were involved in hydrogen bonding interactions with selected ligands. So these interacted residues can be used as prominent active binding sites and which was common to the predicted active site. Based on above investigations it has been found that P. vancouverensis lipase protein can play a similar role in lipid metabolic process and triglyceride lipase functional activity as reported for P. fluorescens lipase protein.

  7. Placental triglyceride accumulation in maternal type 1 diabetes is associated with increased lipase gene expression

    Lindegaard, Marie Louise Skakkebæk; Damm, Peter; Mathiesen, Elisabeth R; Nielsen, Lars B

    2006-01-01

    Maternal diabetes can cause fetal macrosomia and increased risk of obesity, diabetes, and cardiovascular disease in adulthood of the offspring. Although increased transplacental lipid transport could be involved, the impact of maternal type 1 diabetes on molecular mechanisms for lipid transport in...

  8. Lipases and Its Application in Food Industry

    WANG Ting; QIN Gang

    2010-01-01

    Lipases(triacylglycerol acylhydrolases,EC 3.1.1.3)occur widely in nature.It catalyze the hydrolysis and the synthesis of esters formed from glycerol and long-chain fatty acids.Lipases are commercially significant,this article discusses the source,structure,character and preparative method,the applications of lipases in food industry are discussed too.

  9. Profiling of chicken adipose tissue gene expression by genome array

    Wang Shou-Zhi

    2007-06-01

    Full Text Available Abstract Background Excessive accumulation of lipids in the adipose tissue is a major problem in the present-day broiler industry. However, few studies have analyzed the expression of adipose tissue genes that are involved in pathways and mechanisms leading to adiposity in chickens. Gene expression profiling of chicken adipose tissue could provide key information about the ontogenesis of fatness and clarify the molecular mechanisms underlying obesity. In this study, Chicken Genome Arrays were used to construct an adipose tissue gene expression profile of 7-week-old broilers, and to screen adipose tissue genes that are differentially expressed in lean and fat lines divergently selected over eight generations for high and low abdominal fat weight. Results The gene expression profiles detected 13,234–16,858 probe sets in chicken adipose tissue at 7 weeks, and genes involved in lipid metabolism and immunity such as fatty acid binding protein (FABP, thyroid hormone-responsive protein (Spot14, lipoprotein lipase(LPL, insulin-like growth factor binding protein 7(IGFBP7 and major histocompatibility complex (MHC, were highly expressed. In contrast, some genes related to lipogenesis, such as leptin receptor, sterol regulatory element binding proteins1 (SREBP1, apolipoprotein B(ApoB and insulin-like growth factor 2(IGF2, were not detected. Moreover, 230 genes that were differentially expressed between the two lines were screened out; these were mainly involved in lipid metabolism, signal transduction, energy metabolism, tumorigenesis and immunity. Subsequently, real-time RT-PCR was performed to validate fifteen differentially expressed genes screened out by the microarray approach and high consistency was observed between the two methods. Conclusion Our results establish the groundwork for further studies of the basic genetic control of growth and development of chicken adipose tissue, and will be beneficial in clarifying the molecular mechanism of

  10. Crystal Structure of Proteus mirabilis Lipase, a Novel Lipase from the Proteus/Psychrophilic Subfamily of Lipase Family I.1

    Korman, Tyler P; Bowie, James U.

    2012-01-01

    Bacterial lipases from family I.1 and I.2 catalyze the hydrolysis of triacylglycerol between 25–45°C and are used extensively as biocatalysts. The lipase from Proteus mirabilis belongs to the Proteus/psychrophilic subfamily of lipase family I.1 and is a promising catalyst for biodiesel production because it can tolerate high amounts of water in the reaction. Here we present the crystal structure of the Proteus mirabilis lipase, a member of the Proteus/psychrophilic subfamily of I.1lipases. Th...

  11. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality

    Boon, Mariëtte R.; van den Berg, Sjoerd A. A.; Wang, Yanan; van den Bossche, Jan; Karkampouna, Sofia; Bauwens, Matthias; De Saint-Hubert, Marijke; van der Horst, Geertje; Vukicevic, Slobodan; de Winther, Menno P. J.; Havekes, Louis M.; Jukema, J. Wouter; Tamsma, Jouke T.; van der Pluijm, Gabri; van Dijk, Ko Willems; Rensen, Patrick C. N.

    2013-01-01

    Background/Aims Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7 on BAT by treating mice with BMP7 at varying ambient temperature, and assessed the therapeutic potential of BMP7 in combating obesity. Methods and Results High-fat diet fed lean C57Bl6/J mice were treated with BMP7 via subcutaneous osmotic minipumps for 4 weeks at 21°C or 28°C, the latter being a thermoneutral temperature in which sympathetic activation of BAT is largely diminished. At 21°C, BMP7 increased BAT weight, increased the expression of Ucp1, Cd36 and hormone-sensitive lipase in BAT, and increased total energy expenditure. BMP7 treatment markedly increased food intake without affecting physical activity. Despite that, BMP7 diminished white adipose tissue (WAT) mass, accompanied by increased expression of genes related to intracellular lipolysis in WAT. All these effects were blunted at 28°C. Additionally, BMP7 resulted in extensive ‘browning’ of WAT, as evidenced by increased expression of BAT markers and the appearance of whole clusters of brown adipocytes via immunohistochemistry, independent of environmental temperature. Treatment of diet-induced obese C57Bl6/J mice with BMP7 led to an improved metabolic phenotype, consisting of a decreased fat mass and liver lipids as well as attenuated dyslipidemia and hyperglycemia. Conclusion Together, these data show that BMP7-mediated recruitment and activation of BAT only occurs at subthermoneutral temperature, and is thus likely dependent on sympathetic activation of BAT, and that BMP7 may be a promising tool to

  12. Lipoprotein lipase expression exclusively in liver. A mouse model for metabolism in the neonatal period and during cachexia.

    Merkel, M.; Weinstock, P H; Chajek-Shaul, T; Radner, H; B. Yin; Breslow, J L; Goldberg, I J

    1998-01-01

    Lipoprotein lipase (LPL), the rate-limiting enzyme in triglyceride hydrolysis, is normally not expressed in the liver of adult humans and animals. However, liver LPL is found in the perinatal period, and in adults it can be induced by cytokines. To study the metabolic consequences of liver LPL expression, transgenic mice producing human LPL specifically in the liver were generated and crossed onto the LPL knockout (LPL0) background. LPL expression exclusively in liver rescued LPL0 mice from n...

  13. Control of adipose tissue lipolysis in ectotherm vertebrates.

    Migliorini, R H; Lima-Verde, J S; Machado, C R; Cardona, G M; Garofalo, M A; Kettelhut, I C

    1992-10-01

    Lipolytic activity of fish (Hoplias malabaricus), toad (Bufo paracnemis), and snake (Philodryas patagoniensis) adipose tissue was investigated in vivo and in vitro. Catecholamines or glucagon did not affect the release of free fatty acids (FFA) by incubated fish and toad adipose tissue. Catecholamines also failed to activate snake adipose tissue lipolysis, which even decreased in the presence of epinephrine. However, glucagon stimulated both the lipolytic activity of reptilian tissue in vitro and the mobilization of FFA to plasma when administered to snakes in vivo. The release of FFA from incubated fish, amphibian, and reptilian adipose tissue increased markedly in the presence of cAMP or xanthine derivatives, inhibitors of phosphodiesterase. Forskolin or fluoride, activators of specific components of the adenylate cyclase system, strongly stimulated toad adipose tissue lipolysis. The data suggest that adipocyte triacylglycerol lipase of ectotherm vertebrates is activated by a cAMP-mediated phosphorylation and that the organization of the membrane-bound adenylate cyclase system is similar to that of mammals. PMID:1329567

  14. The complete digestion of human milk triacylglycerol in vitro requires gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase.

    Bernbäck, S; Bläckberg, L; Hernell, O

    1990-01-01

    Gastric lipase, pancreatic colipase-dependent lipase, and bile salt-stimulated lipase all have potential roles in digestion of human milk triacylglycerol. To reveal the function of each lipase, an in vitro study was carried out with purified lipases and cofactors, and with human milk as substrate. Conditions were chosen to resemble those of the physiologic environment in the gastrointestinal tract of breast-fed infants. Gastric lipase was unique in its ability to initiate hydrolysis of milk t...

  15. An update on gene therapy for the treatment of lipoprotein lipase deficiency

    Libby AE

    2014-05-01

    Full Text Available Andrew E Libby, Hong Wang Division of Endocrinology, Metabolism, and Diabetes, School of Medicine, University of Colorado at Denver, Aurora, CO, USA Abstract: Lipoprotein lipase (LPL is responsible for clearance of triglyceride-rich lipoproteins from the blood. Deficiency or defects in this enzyme result in profound hypertriglyceridemia and susceptibility to chronic, life-threatening pancreatitis. Management of LPL deficiency has traditionally been restricted to palliative care and strategies to reduce the risk of pancreatitis, including severe dietary restrictions of fat. Recently, the European Commission approved the first gene therapy treatment in the West to treat this rare disease. Alipogene tiparvovec (Glybera® was granted marketing authorization in November 2012 to treat LPL deficiency in a subset of patients that are at increased risk for pancreatitis. Designed as a one-time treatment, the drug uses adeno-associated virus (AAV1 delivery of transgenic LPL to muscle in patients lacking functional enzyme. Although statistically significant reduction of serum triglycerides was initially observed in trial subjects, this effect was found to be transient, with triglyceride levels eventually rebounding to basal levels by 26 weeks in all participants. Nevertheless, despite the return of triglycerides to pretreatment levels, alipogene tiparvovec was found to have a long-term impact on postprandial chylomicron metabolism by lowering the fraction of triglyceride found in this subset of lipoproteins. Furthermore, the drug led to a clinically significant reduction in the incidence of pancreatitis in LPL-deficient patients. The regulatory approval of alipogene tiparvovec was a historic process and serves as an example of the challenges that future orphan drugs will face. Keywords: lipoprotein lipase deficiency, gene therapy, AAV, chylomicron, pancreatitis

  16. The galactolipase activity of Fusarium solani (phospho)lipase.

    Jallouli, Raida; Othman, Houcemeddine; Amara, Sawsan; Parsiegla, Goetz; Carriere, Frédéric; Srairi-Abid, Najet; Gargouri, Youssef; Bezzine, Sofiane

    2015-03-01

    The purified (phospho)lipase of Fusarium solani (FSL), was known to be active on both triglycerides and phospholipids. This study aimed at assessing the potential of this enzyme in hydrolyzing galactolipids. FSL was found to hydrolyze at high rates of synthetic medium chains monogalactosyldiacylglycerol (4658±146U/mg on DiC8-MGDG) and digalactosyldiacylglycerol (3785±83U/mg on DiC8-DGDG) and natural long chain monogalactosyldiacylglycerol extracted from leek leaves (991±85U/mg). It is the microbial enzyme with the highest activity on galactolipids identified so far with a level of activity comparable to that of pancreatic lipase-related protein 2. FSL maximum activity on galactolipids was measured at pH8. The analysis of the hydrolysis product of natural MGDG from leek showed that FSL hydrolyzes preferentially the ester bond at the sn-1 position of galactolipids. To investigate the structure-activity relationships of FSL, a 3D model of this enzyme was built. In silico docking of medium chains MGDG and DGDG and phospholipid in the active site of FSL reveals structural solutions which are in concordance with in vitro tests. PMID:25529980

  17. Lipase biofilm deposited by Matrix Assisted Pulsed Laser Evaporation technique

    Aronne, Antonio; Bloisi, Francesco; Calabria, Raffaela; Califano, Valeria; Depero, Laura E.; Fanelli, Esther; Federici, Stefania; Massoli, Patrizio; Vicari, Luciano R. M.

    2015-05-01

    Lipase is an enzyme that finds application in biodiesel production and for detection of esters and triglycerides in biosensors. Matrix Assisted Pulsed Laser Evaporation (MAPLE), a technique derived from Pulsed Laser Deposition (PLD) for deposition of undamaged biomolecules or polymers, is characterized by the use of a frozen target obtained from a solution/suspension of the guest material (to be deposited) in a volatile matrix (solvent). The presence of the solvent avoids or at least reduces the potential damage of guest molecules by laser radiation but only the guest material reaches the substrate in an essentially solvent-free deposition. MAPLE can be used for enzymes immobilization, essential for industrial application, allowing the development of continuous processes, an easier separation of products, the reuse of the catalyst and, in some cases, enhancing enzyme properties (pH, temperature stability, etc.) and catalytic activity in non-aqueous media. Here we show that MAPLE technique can be used to deposit undamaged lipase and that the complex structure (due to droplets generated during extraction from target) of the deposited material can be controlled by changing the laser beam fluence.

  18. Diacylglycerol synthesis by enzymatic glycerolysis: Screening of commercially available lipases

    Kristensen, Janni Brogaard; Xu, X.B.; Mu, Huiling

    2005-01-01

    suggests that glycerol forms a layer around the hydrophilic lipase particles, limiting contact between the lipases and the hydrophobic oil phase. With glycerol absorbed on silica gel, all lipases catalyzed the glycerolysis reaction. Faster conversion of TAG was obtained with Lipase PS-D, Lipase AK, and...

  19. Lipases in Hierarchically Structured Montmorillonite

    Kuncová, Gabriela; Šabata, Stanislav; Kučerová, L.; Fuzik, T.; Duchek, P.

    - : -, 2011, s. 116-117. ISBN N. [International Conference on Bioencapsulation /19./. Amboise (FR), 05.10.2011-08.10.2011] R&D Projects: GA AV ČR(CZ) IAAX08240901 Institutional research plan: CEZ:AV0Z40720504 Keywords : montmorillonite * lipase * biocatalyst Subject RIV: CC - Organic Chemistry

  20. Structural studies on lipoprotein lipase

    The structure of lipoprotein lipase is not known. The lack of information on its primary sequence has been due to the inability of preparing it in homogeneous and stable form. This research has focused on the structural characterization of lipoprotein lipase. The first approach taken was to develop a purification method using bovine milk and affinity chromatography on heparin-Sepharose. The protein obtained was a heterogeneous peak with the activity shifted towards the trailing edge fractions. These fractions only presented a 55 Kdalton band on polyacrylamide gel electrophoresis. Monoclonal antibodies against this band detected an endogenous, phenyl methane sulfonyl fluoride-sensitive protease responsible for the presence of lower molecular weight fragments. The second approach was to label the lipoprotein lipase with a radioactive, active site, directed probe. After incubation and affinity chromatography a complex [3H]inhibitor enzyme was isolated with a stoichiometry of 1.00 +/- 0.2. The complex was digested with CNBr and the insoluble peptides at low ionic strength (>90% [3H]dpm) were used for further purification. Differential extraction of the [3H]-peptide, digestion with S. aureus V8 protease, and high performance liquid chromatography yielded a hexapeptide with a composition consistent with the consensus sequence of the active site peptides of many serine-esterase. This and the kinetic data imply this being the mechanism of action for lipoprotein lipase

  1. Lipase immobilization for catalytic applications obtained using fumed silica deposited with MAPLE technique

    Bloisi, Francesco; Califano, Valeria; Perretta, Giuseppe; Nasti, Libera; Aronne, Antonio; Di Girolamo, Rocco; Auriemma, Finizia; De Rosa, Claudio; Vicari, Luciano R. M.

    2016-06-01

    Lipases are enzymes used for catalyzing reactions of acylglycerides in biodiesel production from lipids, where enzyme immobilization on a substrate is required. Silica nanoparticles in different morphologies and configurations are currently used in conjunction with biological molecules for drug delivery and catalysis applications, but up to date their use for triglycerides has been limited by the large size of long-chain lipid molecules. Matrix assisted pulsed laser evaporation (MAPLE), a laser deposition technique using a frozen solution/suspension as a target, is widely used for deposition of biomaterials and other delicate molecules. We have carried out a MAPLE deposition starting from a frozen mixture containing fumed silica and lipase in water. Deposition parameters were chosen in order to increase surface roughness and to promote the formation of complex structures. Both the target (a frozen thickened mixture of nanoparticles/catalyst in water) and the deposition configuration (a small target to substrate distance) are unusual and have been adopted in order to increase surface contact of catalyst and to facilitate access to long-chain molecules. The resulting innovative film morphology (fumed silica/lipase cluster level aggregation) and the lipase functionality (for catalytic biodiesel production) have been studied by FESEM, FTIR and transesterification tests.

  2. m-DOPA addition in MAPLE immobilization of lipase for biosensor applications

    Valeria Califano

    2015-12-01

    Full Text Available Matrix Assisted Pulsed Laser Evaporation (MAPLE is a thin film deposition technique which uses a pulsed laser beam impinging, inside a high vacuum chamber, on a frozen target containing the guest molecules in a volatile matrix to induce fast “evaporation” of the matrix, and ejection of the guest molecules. Lipase, an enzyme acting as a catalyst in hydrolysis of lipids, is widely used in biosensors for detection of triglycerides in blood serum. A key action to this purpose is lipase immobilization on a substrate. In a recent paper, we have shown that MAPLE technique is able to deposit lipase on a substrate in an active form. Here we show that addition to the guest/matrix target of a small amount of m-DOPA (3-(3,4-dihydroxyphenyl-2-methyl-l-alanine in order to improve adhesion and protect lipase secondary structure, also allows the lowering the laser pulse energy required for matrix evaporation and therefore the risk of damaging the enzyme.

  3. Immobilization of lipase and keratinase on functionalized SBA-15 nanostructured materials

    Le, Hy G.; Vu, Tuan A.; Tran, Hoa T. K.; Dang, Phuong T.

    2013-12-01

    SBA-15 nanostructured materials were synthesized via hydrothermal treatment and were functionalized with 3- aminopropyltriethoxysilane (APTES). The obtained samples were characterized by different techniques such as XRD, BET, TEM, IR and DTA. After functionalization, it showed that these nanostrucrured materials still maintained the hexagonal pore structure of the parent SBA-15. The model enzyms chosen in this study were lipase and keratinase. Lipase was a biocatalyst for hydrolyzation of long chain triglycerides or methyl esters of long chain alcohols and fatty acids; keratinase is a proteolytic enzyme that catalyzes the cleavage of keratin. The functionalized SBA-15 materials were used to immobilize lipase and keratinase, exhibiting higher activity than that of the unfunctionalized pure silica SBA-15 ones. This might be due to the enhancing of surface hydrophobicity upon functionalization. The surface functionalization of the nanostructured silicas with organic groups can favor the interaction between enzyme and the supports and consequently increasing the operational stability of the immobilized enzymes. The loading of lipase on functionalized SBA-15 materials was higher than that of keratinase. This might be rationalized by the difference in size of enzyms.

  4. Targeted disruption of hormone-sensitive lipase results in male sterility and adipocyte hypertrophy, but not in obesity

    Osuga, Jun-ichi; Ishibashi, Shun; Oka, Teruaki; Yagyu, Hiroaki; Tozawa, Ryuichi; Fujimoto, Akihisa; Shionoiri, Futoshi; Yahagi, Naoya; Kraemer, Frederic B.; Tsutsumi, Osamu; Yamada, Nobuhiro

    2000-01-01

    Hormone-sensitive lipase (HSL) is known to mediate the hydrolysis not only of triacylglycerol stored in adipose tissue but also of cholesterol esters in the adrenals, ovaries, testes, and macrophages. To elucidate its precise role in the development of obesity and steroidogenesis, we generated HSL knockout mice by homologous recombination in embryonic stem cells. Mice homozygous for the mutant HSL allele (HSL−/−) were superficially normal except that the males were...

  5. The Role of Triglycerides in Atherosclerosis

    Talayero, Beatriz G.; Sacks, Frank M.

    2011-01-01

    Hypertriglyceridemia is a prevalent risk factor for cardiovascular disease (CVD) and increasingly important in the setting of current obesity and insulin resistance epidemics. High triglyceride (TG) levels are markers for several types of atherogenic lipoproteins. Patients who have hypertriglyceridemia may be at significant risk for CVD even if low-density lipoprotein cholesterol levels are at goal, and therefore warrant treatment that optimizes diet, reduces overweight, and promotes regular ...

  6. The Triglyceride-to-HDL Cholesterol Ratio

    Giannini, Cosimo; Santoro, Nicola; Caprio, Sonia; Kim, Grace; Lartaud, Derek; Shaw, Melissa; Pierpont, Bridget; Weiss, Ram

    2011-01-01

    OBJECTIVE We evaluated whether the triglyceride-to-HDL cholesterol (TG/HDL-C) ratio is associated with insulin resistance (IR) in a large multiethnic cohort of obese youths. RESEARCH DESIGN AND METHODS Obese youths (1,452) had an oral glucose tolerance test and a fasting lipid profile. Insulin sensitivity was estimated using the whole body insulin sensitivity index (WBISI) and homeostasis model assessment (HOMA)-IR and evaluated, in a subgroup of 146 obese youths, by the hyperinsulinemic-eugl...

  7. Botulinum toxin injections to reduce adiposity: possibility, or fat chance?

    Lim, Erle C H; Seet, Raymond C S

    2006-01-01

    Obese individuals often suffer from negative self-image. Many, even those with a normal body mass index, resort to pharmacotherapy (lipase inhibitors or appetite suppressants), mesotherapy and surgery (gastric volume reduction, liposuction or apronectomy) in a bid to remove excess adipose tissue. These treatments are associated with inherent morbidity and even mortality, and hence should not be undertaken lightly. The observation that denervation of adipose tissue results in lipoatrophy leads us to postulate that chemodenervation using botulinum toxin may achieve the same result, i.e. fat loss, and we explore the methods by which selective fat loss may be achieved. We concede that removal of subcutaneous fat does not, however, reduce the risks associated with the metabolic syndrome, as visceral (intra-abdominal) fat is not reduced by the removal of subcutaneous fat. PMID:16716533

  8. Nonfasting triglycerides, cholesterol, and ischemic stroke in the general population

    Varbo, Anette; Nordestgaard, Børge G; Tybjaerg-Hansen, Anne;

    2011-01-01

    Current guidelines on stroke prevention have recommendations on desirable cholesterol levels, but not on nonfasting triglycerides. We compared stepwise increasing levels of nonfasting triglycerides and cholesterol for their association with risk of ischemic stroke in the general population....

  9. MICROBIAL LIPASES: PRODUCTION OF EXTRACELLULAR LIPASE ENZYME BY ALCALIGENES VISCOSUS (DOGE-1) STRAIN

    P.Sekhar

    2012-01-01

    Industrially important extracellular lipase enzyme production was explored by utilizingmicrobial strain isolated from dairy effluents. Alcaligenes viscosus DOGE-1 strain isolated from dairywaste waters proved to produce extracellular lipase. Various growth factors were attempted to maximizethe lipase production by this strain. Growth factors like NH4PO4, Peptone, Urea coupled with peptone,KH2PO4, Olive oil and pH were found to be favored the maximum lipase production. This microbialstrain was...

  10. Study of Antiobesity Effect through Inhibition of Pancreatic Lipase Activity of Diospyros kaki Fruit and Citrus unshiu Peel

    Kim, Gyo-Nam; Shin, Mi-Rae; Shin, Sung Ho; Lee, Ah Reum; Lee, Joo Young; Seo, Bu-Il; Kim, Min Yeong; Kim, Tae Hoon; Noh, Jeong Sook; Rhee, Man Hee

    2016-01-01

    Pancreatic lipase is the enzyme responsible for digestion and absorption of triglycerides, being its inhibition one of the widest studied methods used to determine the potential activity of natural products to inhibit dietary fat absorption. Decrease of energy intake from dietary fat through inhibition of this enzyme may be an excellent strategy to prevent and treat obesity. The inhibitory activity on pancreatic lipase enzyme of Diospyros kaki fruit and Citrus unshiu peel mixture extract (PCM) was evaluated in vitro and its antiobesity effects were studied based on the serum lipid parameters analysis from high-fat diet- (HFD-) fed mice in vivo. PCM was orally administered at a dose of 50 and 200 mg/kg body weight for 6 weeks. In addition, the activity of pancreatic lipase was assessed using orlistat (positive control). PCM exhibited inhibitory effect on lipase activity with IC50 value of 507.01 μg/mL. Moreover, serum triacylglycerol, total cholesterol levels, and visceral fat weight were significantly reduced compared to HFD control mice in PCM 200 mg/kg-treated mice (p absorption via inhibition of pancreatic lipase. PMID:27529064

  11. Production of an acidic and thermostable lipase of the mesophilic fungus Penicillium simplicissimum by solid-state fermentation.

    Gutarra, Melissa L E; Godoy, Mateus G; Maugeri, Francisco; Rodrigues, Maria Isabel; Freire, Denise M G; Castilho, Leda R

    2009-11-01

    The production of a lipase by a wild-type Brazilian strain of Penicillium simplicissimum in solid-state fermentation of babassu cake, an abundant residue of the oil industry, was studied. The enzyme production reached about 90 U/g in 72 h, with a specific activity of 4.5 U/mg of total proteins. The crude lipase showed high activities at 35-60 degrees C and pH 4.0-6.0, with a maximum activity at 50 degrees C and pH 4.0-5.0. Enzyme stability was enhanced at pH 5.0 and 6.0, with a maximum half-life of 5.02 h at 50 degrees C and pH 5.0. Thus, this lipase shows a thermophilic and thermostable behavior, what is not common among lipases from mesophilic filamentous fungi. The crude enzyme catalysed the hydrolysis of triglycerides and p-nitrophenyl esters (C4:0-C18:0), preferably acting on substrates with medium-chain fatty acids. This non-purified lipase in addition to interesting properties showed a reduced production cost making feasible its applicability in many fields. PMID:19560339

  12. Anti-obesity effect of Dioscorea nipponica Makino with lipase-inhibitory activity in rodents.

    Kwon, Chong-Suk; Sohn, Ho Yong; Kim, Sung Hee; Kim, Ji Hyun; Son, Kun Ho; Lee, Jeong Soon; Lim, Jin Kyu; Kim, Jong-Sang

    2003-07-01

    In the process of screening for pancreatic lipase inhibitors, which could be used as an anti-obesity measure, the methanol extract of Dioscorea nipponica Makino powder (DP) appeared to have potent inhibitory activity against porcine pancreatic lipase with an IC50 value of 5-10 microg/ml, where the enzyme activity was assayed by using 4-methylumbelliferyl oleate as a substrate. Further purification of active components present in the herb generated dioscin that belongs to the saponin family. Dioscin and its aglycone, diosgenin, both suppressed the time-dependent increase of blood triacylglycerol level when orally injected with corn oil to mice, suggesting their inhibitory potential against fat absorption. Sprague-Dawley rats fed on a high-fat diet containing 5% Dioscorea nipponica Makino and 40% beef tallow gained significantly less body weight and adipose tissue than control animals fed on a high-fat diet alone during an 8-week experimental period (P<0.05). PMID:12913286

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

    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

  14. Serum pancreatic lipase activity in cystic fibrosis.

    Junglee, D; Penketh, A; Katrak, A; Hodson, M.E.; Batten, J C; Dandona, P

    1983-01-01

    Patients with cystic fibrosis have been found to have abnormal serum concentrations of immunoreactive trypsin and abnormal activities of pancreatic isoamylase. A study was undertaken to discover whether activity of pancreatic lipase is also altered in cystic fibrosis. Serum from 23 patients with cystic fibrosis was assayed for immunoreactive trypsin and pancreatic lipase. Median serum pancreatic lipase activity was significantly lower in patients with cystic fibrosis than in controls, as was ...

  15. 21 CFR 184.1415 - Animal lipase.

    2010-04-01

    ... ed. (1981), p. 110, which is incorporated by reference in accordance with 5 U.S.C. 552(a) and 1 CFR... 21 Food and Drugs 3 2010-04-01 2009-04-01 true Animal lipase. 184.1415 Section 184.1415 Food and... Substances Affirmed as GRAS § 184.1415 Animal lipase. (a) Animal lipase (CAS Reg. No. 9001-62-1) is an...

  16. Neural Innervation of White Adipose Tissue and the Control of Lipolysis

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

    2014-01-01

    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 by electrophysiological and neurochemical (NE turnover) in non-human animals and this ...

  17. BMP8B Increases Brown Adipose Tissue Thermogenesis through Both Central and Peripheral Actions

    Whittle AJ; Carobbio S; Martins L; Slawik M; Hondares E; V\\xe1zquez MJ; Morgan D; Csikasz RI; Gallego R; Rodriguez-Cuenca S; Dale M.; Virtue S; Villarroya F; Cannon B; Rahmouni K

    2012-01-01

    Summary Thermogenesis in brown adipose tissue (BAT) is fundamental to energy balance and is also relevant for humans. Bone morphogenetic proteins (BMPs) regulate adipogenesis, and, here, we describe a role for BMP8B in the direct regulation of thermogenesis. BMP8B is induced by nutritional and thermogenic factors in mature BAT, increasing the response to noradrenaline through enhanced p38MAPK/CREB signaling and increased lipase activity. Bmp8b−/− mice exhibit impaired thermogenesis and reduce...

  18. Patient Guide to the Assessment and Treatment of Hypertriglyceridemia (High Triglycerides)

    Assessment and Treatment of Hypertriglyceridemia (High Triglycerides) A Patient’s Guide Having high levels of triglycerides, or hypertriglyceridemia , is a common problem. Triglycerides are fats in ...

  19. Ikkefastende triglycerider og risiko for iskamisk apopleksi--sekundaerpublikation

    Freiberg, Jacob J; Tybjaerg-Hansen, Anne; Jensen, Jan Skov; Nordestgaard, Børge G

    2009-01-01

    hazard ratio for ischemic stroke of 2.5 (95% confidence interval: 1.3-4.8) compared with men with a nonfasting triglyceride level < 1 mmol/l. The corresponding value in women was 3.8 (1.3-11). We conclude that the level of nonfasting triglycerides is associated with risk of ischemic stroke......The role of triglycerides in the risk of ischemic stroke remains controversial. We tested the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Men with a nonfasting triglyceride level 5 mmol/l had a multivariable, adjusted...

  20. [Nonfasting triglycerides and risk of ischemic stroke--secondary publication

    Freiberg, J.J.; Tybjaerg-Hansen, A.; Jensen, J.S.; Nordestgaard, B.G.

    2009-01-01

    hazard ratio for ischemic stroke of 2.5 (95% confidence interval: 1.3-4.8) compared with men with a nonfasting triglyceride level < 1 mmol/l. The corresponding value in women was 3.8 (1.3-11). We conclude that the level of nonfasting triglycerides is associated with risk of ischemic stroke Udgivelsesdato......The role of triglycerides in the risk of ischemic stroke remains controversial. We tested the hypothesis that increased levels of nonfasting triglycerides are associated with ischemic stroke in the general population. Men with a nonfasting triglyceride level 5 mmol/l had a multivariable, adjusted...

  1. Lipase Activity of Guinea Pig Peritoneal Macrophages and Mycobacterial Lipase Inhibitor

    Kiyotani, Katsuhiro; Tasaka, Hiromichi; Tsukiyama, Fumiaki; Matsuo, Yoshiyasu

    1983-01-01

    The interaction of mycobacterial lipase inhibitor (MLI), isolated from culture supernatant fluid of Mycobacterium tuberculosis strain H37Rv, and lipase from guinea pig peritoneal macrophages (GP-PMφs) was investigated fluorimetrically by the modified lipase assay system which had previously been proposed. Two peaks of lipase activity were observed in the enzyme preparation from GPPMφs. The activity of MLI against lipase from GP-PMφs was significantly high at acidic pH less than 5.0, and t...

  2. Reduction of Adipose Tissue Mass by the Angiogenesis Inhibitor ALS-L1023 from Melissa officinalis.

    Byung Young Park

    Full Text Available It has been suggested that angiogenesis modulates adipogenesis and obesity. This study was undertaken to determine whether ALS-L1023 (ALS prepared by a two-step organic solvent fractionation from Melissa leaves, which exhibits antiangiogenic activity, can regulate adipose tissue growth. The effects of ALS on angiogenesis and extracellular matrix remodeling were measured using in vitro assays. The effects of ALS on adipose tissue growth were investigated in high fat diet-induced obese mice. ALS inhibited VEGF- and bFGF-induced endothelial cell proliferation and suppressed matrix metalloproteinase (MMP activity in vitro. Compared to obese control mice, administration of ALS to obese mice reduced body weight gain, adipose tissue mass and adipocyte size without affecting appetite. ALS treatment decreased blood vessel density and MMP activity in adipose tissues. ALS reduced the mRNA levels of angiogenic factors (VEGF-A and FGF-2 and MMPs (MMP-2 and MMP-9, whereas ALS increased the mRNA levels of angiogenic inhibitors (TSP-1, TIMP-1, and TIMP-2 in adipose tissues. The protein levels of VEGF, MMP-2 and MMP-9 were also decreased by ALS in adipose tissue. Metabolic changes in plasma lipids, liver triglycerides, and hepatic expression of fatty acid oxidation genes occurred during ALS-induced weight loss. These results suggest that ALS, which has antiangiogenic and MMP inhibitory activities, reduces adipose tissue mass in nutritionally obese mice, demonstrating that adipose tissue growth can be regulated by angiogenesis inhibitors.

  3. Enhanced activity of hormone sensitive lipase (HSL) in mesenteric but not epididymal fat correlates with higher production of epinephrine in mesenteric adipocytes in rat model of cachectic rheumatoid arthritis.

    Stofkova, Andrea; Krskova, Katarina; Vaculin, Simon; Jurcovicova, Jana

    2016-06-01

    Cachectic rheumatoid arthritis, the less frequent form of the disease, is associated with loss of fat mass and often more severe course of the disease. Its experimental model represents rat adjuvant arthritis (AA) characterized by edema, lack of appetite, sharp body weight and fat loss. As individual fat depots display functional differences, here we studied lipolytic activity and sensitivity to lipolytic stimuli of nodeless epididymal fat (eWAT) and perinodal mesenteric fat (mWAT) depots at the peak of AA. We also examined changes in catecholamine and cytokine levels involved in lipolysis in plasma and/or isolated adipocytes from both WATs to identify the contribution of local, adipocyte-based processes and/or systemic events to adiposity loss in cachectic rheumatoid arthritis. AA was induced to male Lewis rats by complete Freund's adjuvant. Groups of ad libitum-fed and pair-fed controls were used to distinguish the effects of food restriction from inflammation-induced cachexia. Adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL) and its phosphorylated form (pHSL) were analyzed by western blot. CRP and catecholamine levels in plasma or adipocyte lysates were determined using ELISA kits. Cytokine-induced neutrophil chemoattractant-1 (CINC-1/CXCL1), monocyte chemoattractant protein-1 (MCP-1/CCL2), IL-1β, IL-6, IL-10 and leptin in adipocyte lysate were analyzed by quantitative protein microarray. Plasma glycerol and FFA were measured spectrophotometrically. AA rats developed severe cachexia, with lower adiposity in mWAT compared to normal and pair-fed controls, whereas in eWAT the adiposity was similarly reduced in AA and pair-fed groups. ATGL levels in both WATs were not affected by AA or pair feeding. AA upregulated levels of HSL, pHSL and pHSL/HSL ratio in mWAT, whereas none of these parameters has changed in eWAT of AA rats or in either WATs of pair-fed rats. In AA rats plasma glycerol was elevated, whereas FFA concentration was reduced. Plasma

  4. Organic Solvent Tolerant Lipases and Applications

    Shivika Sharma

    2014-01-01

    Full Text Available Lipases are a group of enzymes naturally endowed with the property of performing reactions in aqueous as well as organic solvents. The esterification reactions using lipase(s could be performed in water-restricted organic media as organic solvent(s not only improve(s the solubility of substrate and reactant in reaction mixture but also permit(s the reaction in the reverse direction, and often it is easy to recover the product in organic phase in two-phase equilibrium systems. The use of organic solvent tolerant lipase in organic media has exhibited many advantages: increased activity and stability, regiospecificity and stereoselectivity, higher solubility of substrate, ease of products recovery, and ability to shift the reaction equilibrium toward synthetic direction. Therefore the search for organic solvent tolerant enzymes has been an extensive area of research. A variety of fatty acid esters are now being produced commercially using immobilized lipase in nonaqueous solvents. This review describes the organic tolerance and industrial application of lipases. The main emphasis is to study the nature of organic solvent tolerant lipases. Also, the potential industrial applications that make lipases the biocatalysts of choice for the present and future have been presented.

  5. The photo biological effect of low level laser therapy on serum level of leptin, cholesterol and triglycerides in overweight and obese females

    The use of low level laser for body contouring and weight reduction depends on the photochemical non thermal effect of laser light on the adipose tissue. LLLT was reported to liquefy or release stored fat in adipocytes by the opening of specialized yet not identified cell membrane-associated pores after a brief treatment The concentration of leptin in adipose tissue and serum closely parallel the mass of adipose tissue and adipocyte size and triglycerides content. Thus, leptin increases in obesity and falls with weight loss. The current study was conducted to evaluate the effect of the low level laser therapy (LLLT) on leptin hormone, Cholesterol and triglyceride in both overweight and obese females. Twenty women were included in this study. Their ages ranged from 30-40 years. They were divided into two equal groups. Group A (Overweight group): included 10 females with BMI between 25 and 29.9 Kg/m2 -Group B (Obese group): included 10 females with BMI . 30. Both groups received LLL to the abdomen using laser scanner for uniform distribution of the beam above and below the umbilicus. Duration of treatment was 30 minutes, 2 times per week for 8 weeks as a total period of treatment. Serum level of leptin was estimated by radioimmunoassay (RIA). As regards serum cholesterol and triglyceride they were determined by enzymatic colorimetric test. Biochemical assessments were done before and after treatment. Results of the present study showed that in the overweight group laser treatment resulted in highly significant reduction in leptin serum level accompanied by highly significant increase in serum triglycerides level. Meanwhile, the increase in cholesterol level was insignificant. As regards the obese group, alteration in serum leptin level caused by laser treatment was not significant. In this group the increase in triglycerides and cholesterol serum levels after treatment were highly significant

  6. Visceral adiposity syndrome.

    Lopes, Heno F; Corrêa-Giannella, Maria Lúcia; Consolim-Colombo, Fernanda M; Egan, Brent M

    2016-01-01

    The association of anthropometric (waist circumference) and hemodynamic (blood pressure) changes with abnormalities in glucose and lipid metabolism has been motivation for a lot of discussions in the last 30 years. Nowadays, blood pressure, body mass index/abdominal circumference, glycemia, triglyceridemia, and HDL-cholesterol concentrations are considered in the definition of Metabolic syndrome, referred as Visceral adiposity syndrome (VAS) in the present review. However, more than 250 years ago an association between visceral and mediastinal obesity with hypertension, gout, and obstructive apnea had already been recognized. Expansion of visceral adipose tissue secondary to chronic over-consumption of calories stimulates the recruitment of macrophages, which assume an inflammatory phenotype and produce cytokines that directly interfere with insulin signaling, resulting in insulin resistance. In turn, insulin resistance (IR) manifests itself in various tissues, contributing to the overall phenotype of VAS. For example, in white adipose tissue, IR results in lipolysis, increased free fatty acids release and worsening of inflammation, since fatty acids can bind to Toll-like receptors. In the liver, IR results in increased hepatic glucose production, contributing to hyperglycemia; in the vascular endothelium and kidney, IR results in vasoconstriction, sodium retention and, consequently, arterial hypertension. Other players have been recognized in the development of VAS, such as genetic predisposition, epigenetic factors associated with exposure to an unfavourable intrauterine environment and the gut microbiota. More recently, experimental and clinical studies have shown the autonomic nervous system participates in modulating visceral adipose tissue. The sympathetic nervous system is related to adipose tissue function and differentiation through beta1, beta2, beta3, alpha1, and alpha2 adrenergic receptors. The relation is bidirectional: sympathetic denervation of

  7. Cultured human astrocytes secrete large cholesteryl ester- andtriglyceride-rich lipoproteins along with endothelial lipase

    Yang, Lin; Liu, Yanzhu; Forte, Trudy M.; Chisholm, Jeffrey W.; Parks, John S.; Shachter, Neil S.

    2003-12-01

    We cultured normal human astrocytes and characterized their secreted lipoproteins. Human astrocytes secreted lipoproteins in the size range of plasma VLDL (Peak 1), LDL (Peak 2), HDL (Peak 3) and a smaller peak (Peak 4), as determined by gel filtration chromatography, nondenaturing gradient gel electrophoresis and transmission electron microscopy. Cholesterol enrichment of astrocytes led to a particular increase in Peak 1. Almost all Peak 2, 3 and 4 cholesterol and most Peak 1 cholesterol was esterified (unlike mouse astrocyte lipoproteins, which exhibited similar peaks but where cholesterol was predominantly non-esterified). Triglycerides were present at about 2/3 the level of cholesterol. LCAT was detected along with two of its activators, apolipoprotein (apo) A-IV and apoC-I. ApoA-I and apoA-II mRNA and protein were absent. ApoJ was present equally in all peaks but apoE was present predominantly in peaks 3 and 4. ApoB was not detected. The electron microscopic appearance of Peak 1 lipoproteins suggested partial lipolysis leading to the detection of a heparin-releasable triglyceride lipase consistent with endothelial lipase. The increased neuronal delivery of lipids from large lipoprotein particles, for which apoE4 has greater affinity than does apoE3, may be a mechanism whereby the apoE {var_epsilon}4 allele contributes to neurodegenerative risk.

  8. Lipoprotein lipase is produced, regulated, and functional in rat brain.

    Eckel, R.H.; Robbins, R J

    1984-01-01

    Lipoprotein lipase (LP lipase, triacylglycero-protein acylhydrolase EC 3.1.1.34) activity was found in four dissimilar brain regions (hypothalamus, cortex, cerebellum, and midbrain) of adult male rats. Progressive accumulation of LP lipase activity in cultured fetal rat hypothalamic cells was also observed, indicating de novo synthesis of the lipase. The brain LP lipase activity was serum-dependent and was inhibited by 1 M NaCl and by protamine sulfate. Kinetic analysis revealed an apparent K...

  9. Neutrophil chemotaxis by Propionibacterium acnes lipase and its inhibition.

    Lee, W. L.; Shalita, A R; Suntharalingam, K; Fikrig, S M

    1982-01-01

    The chemoattraction of Propionibacterium acnes lipase for neutrophils and the effect of lipase inhibitor and two antibiotic agents on the chemotaxis were evaluated. Of the various fractions tested, partially purified lipase (fraction 2c) was the most active cytotaxin produced by P. acnes. Serum mediators were not required for the generation of chemotaxis by lipase in vitro. Diisopropyl phosphofluoridate at low concentration (10(-4) mM) completely inhibited lipase activity as well as polymorph...

  10. The synthetic pentasaccharide SR 90107A/Org 31540 does not release lipase activity into the plasma.

    Hoffmann, P; Bernat, A; Dumas, A; Petitou, M; Hérault, J P; Herbert, J M

    1997-05-15

    The present study was designed to find out whether the synthetic pentasaccharide SR 90107A/Org 31540, which is presently being evaluated in clinical trials as an antithrombotic agent, influences lipoprotein metabolism in rats as determined by plasma triglyceride (TG) lipase activity. A comparison with three clinically used sulphated polysaccharides-unfractionated heparin (UFH), low molecular weight heparin (LMWH) and pentosan polysulphate (PPS)- was performed. UFH evoked a dose-dependent increase in plasma TG lipase activity which plateaued at doses > or = 1 mg/kg i.v.. PPS and LMWH demonstrated a lower efficacy than heparin at 0.3 and 1 mg/kg i.v., but the maximum lipase releasing effect at 3 mg/kg i.v. was identical for UFH, PPS and LMWH. SR 90107A/Org 31540 did not release TG lipase activity at single i.v. doses up to 3 mg/kg. Repeated-dose experiments with SR 90107A/Org 31540 (1 mg/kg s.c. for 9 days) revealed no influence on the lipase releasing effect of UFH (1 mg/kg i.v. on day 10). These results demonstrate that SR 90107A/Org 31540 does not influence lipid metabolism in rats through lipase release, suggesting that SR 90107A/Org 31540 may offer an advantage over UFH and LMWH in clinical situations where an anticoagulant/antithrombotic effect is desired, but both an increase in plasma free fatty acids and atherogenic alterations of lipoprotein metabolism are considered harmful. PMID:9187020

  11. Adsorption of gastric lipase onto multicomponent model lipid monolayers with phase separation.

    Bourlieu, Claire; Paboeuf, Gilles; Chever, Sophie; Pezennec, Stéphane; Cavalier, Jean-François; Guyomarc'h, Fanny; Deglaire, Amélie; Bouhallab, Saïd; Dupont, Didier; Carrière, Frédéric; Vié, Véronique

    2016-07-01

    The enzymatic lipolysis of complex natural lipoproteic assemblies such as milk fat globules is central in neonatal digestion. This process first requires the rapid adsorption of a lipolytic enzyme, gastric lipase, onto the membrane enveloping the triglyceride substrate before the onset of catalytic activity. The interactions governing lipase adsorption onto this complex lipid/water interface are not fully elucidated. This study was designed to unravel the interactions of recombinant dog gastric lipase (rDGL) with model monolayers presenting liquid-liquid phase coexistence and mimicking the outer leaflet of the milk fat globule membrane. Combining biophysical tools (ellipsometry, tensiometry and atomic force microscopy), it was evidenced that rDGL partitions toward liquid expanded phase and at phase boundaries. rDGL gets adsorbed at several levels of insertion suggesting molecular cooperation that may favor insertion and strongly impacts on the lipid phase lateral organization. The addition of phosphatidylserine, negatively charged, reinforced adsorption; hence besides hydrophobic interactions and as further investigated through surface potential modeling, rDGL adsorption is favored by electrostatic interactions. PMID:27011347

  12. Uremic Toxins and Lipases in Haemodialysis: A Process of Repeated Metabolic Starvation

    Bernd Stegmayr

    2014-04-01

    Full Text Available Severe kidney disease results in retention of uremic toxins that inhibit key enzymes for lipid breakdown such as lipoprotein lipase (LPL and hepatic lipase (HL. For patients in haemodialysis (HD and peritoneal dialysis (PD the LPL activity is only about half of that of age and gender matched controls. Angiopoietin, like protein 3 and 4, accumulate in the uremic patients. These factors, therefore, can be considered as uremic toxins. In animal experiments it has been shown that these factors inhibit the LPL activity. To avoid clotting of the dialysis circuit during HD, anticoagulation such as heparin or low molecular weight heparin are added to the patient. Such administration will cause a prompt release of the LPL and HL from its binding sites at the endothelial surface. The liver rapidly degrades the release plasma compound of LPL and HL. This results in a lack of enzyme to degrade triglycerides during the later part of the HD and for another 3–4 h. PD patients have a similar baseline level of lipases but are not exposed to the negative effect of anticoagulation.

  13. Adipose Tissue Metabolism During Hypobaria

    D. P. Chattopadhyay

    1974-10-01

    Full Text Available Possible factors affecting the metabolism of adipose tissue under hypobaric conditions have been reviewed. The hormonal changes brought into play under hypoxic stress generally stress generally increase the adipose tissue lipolysis.

  14. Microbial Lipases and Their Industrial Applications: Review

    Berhanu Andualema

    2012-01-01

    Full Text Available Microbial lipases (triacylglycerol acyl-hydrolases, EC 3.1.1.3 catalyze both the hydrolysis and synthesis of long-chain acylglycerols. They are currently given much attention with the rapid development of enzyme technology. The chemo-, regio- and enantio-specific characteristics of lipase tends to be a focus research area for scientists and industrialists. Compared to plants and animals, microorganisms have been found to produce high yields of lipases. This review describes various industrial applications of microbial lipases in the area of food industry, oil and fat industry, detergent industry, pulp and paper industry, leather industry, textile industry, in organic synthesis, production of cosmetics and biodiesel production. This makes lipases the most widely used class of enzymes in different industrial activities through the application of bioprocess technology. The aim of this review is not to discuss every lipase described in the literature but rather to present recent information on the production, characterization and industrial application of lipases in our daily activities in order to improve our life styles.

  15. Impact of lipoprotein lipase gene polymorphisms on ulcerative colitis

    Toshihito Kosaka; Taizou Shiraishi; Masatoshi Watanabe; Takayuki Yamamoto; Ai Nakahara; Takahiko Katoh; Junji Yoshino; Kazuo Inui; Takao Wakabayashi; Kazumu Okushima; Takashi Kobayashi; Hironao Miyoshi; Yuta Nakamura; Shigekazu Hayashi

    2006-01-01

    AIM: To examine the influence of lipoprotein lipase (LPL)gene polymorphism in ulcerative colitis (UC) patients.METHODS: Peripheral blood was obtained from 131 patients with UC and 106 healthy controls for DNA extraction. We determined LPL gene polymorphisms affecting the enzyme at Ser447stop, as well as Hind Ⅲ and Pvu Ⅱ polymorphisms using PCR techniques. PCR products were characterized by PCR-RFLP and direct sequencing.Polymorphisms were examined for association with clinical features in UC patients. Genotype frequencies for LPL polymorphisms were also compared between UC patients and controls.RESULTS: In patients with onset at age 20 years or younger, C/G and G/G genotypes for Ser447stop polymorphism were more prevalent than C/C genotype (OR= 3.13, 95% CI = 0.95-10.33). Patients with H+/- or H-/-genotype for HindⅢ polymorphism also were more numerous than those with H+/+ genotype (OR = 2.51, 95%CI = 0.85-7.45). In the group with H+/+ genotype for HindⅢ polymorphism, more patients had serum triglyceride concentrations over 150 mg/dL than patients with H+/- or H-/- genotype (P < 0.01, OR = 6.46, 95% CI =1.39-30.12). Hypertriglycemia was also more prevalent in patients with P+/+ genotypes for Pvu Ⅱ polymorphism (P< 0.05, OR = 3.0, 95% CI = 1.06-8.50). Genotype frequency for LPL polymorphism did not differ significantly between UC patients and controls.CONCLUSION: Ser447stop and HindⅢ LPL polymorphisms may influence age of onset of UC, while HindⅢand PvuⅡ polymorphisms influence serum triglyceride in UC patients.

  16. ANGPTL4 variants E40K and T266M are associated with lower fasting triglyceride levels in Non-Hispanic White Americans from the Look AHEAD Clinical Trial

    Pownall Henry J

    2011-06-01

    Full Text Available Abstract Background Elevated triglyceride levels are a risk factor for cardiovascular disease. Angiopoietin-like protein 4 (Angptl4 is a metabolic factor that raises plasma triglyceride levels by inhibiting lipoprotein lipase (LPL. In non-diabetic individuals, the ANGPTL4 coding variant E40K has been associated with lower plasma triglyceride levels while the T266M variant has been associated with more modest effects on triglyceride metabolism. The objective of this study was to determine whether ANGPTL4 E40K and T266M are associated with triglyceride levels in the setting of obesity and T2D, and whether modification of triglyceride levels by these genetic variants is altered by a lifestyle intervention designed to treat T2D. Methods The association of ANGPTL4 E40K and T266M with fasting triglyceride levels was investigated in 2,601 participants from the Look AHEAD Clinical Trial, all of whom had T2D and were at least overweight. Further, we tested for an interaction between genotype and treatment effects on triglyceride levels. Results Among non-Hispanic White Look AHEAD participants, ANGPTL4 K40 carriers had mean triglyceride levels of 1.61 ± 0.62 mmol/L, 0.33 mmol/L lower than E40 homozygotes (p = 0.001. Individuals homozygous for the minor M266 allele (MAF 30% had triglyceride levels of 1.75 ± 0.58 mmol/L, 0.24 mmol/L lower than T266 homozygotes (p = 0.002. The association of the M266 with triglycerides remained significant even after removing K40 carriers from the analysis (p = 0.002. There was no interaction between the weight loss intervention and genotype on triglyceride levels. Conclusions This is the first study to demonstrate that the ANGPTL4 E40K and T266M variants are associated with lower triglyceride levels in the setting of T2D. In addition, our findings demonstrate that ANGPTL4 genotype status does not alter triglyceride response to a lifestyle intervention in the Look AHEAD study.

  17. Plasma apolipoprotein A5 and triglycerides in type 2 diabetes

    Dallinga-Thie, GM; Van Tol, A; Hattori, H; van Vark-van de Zee, LC; Jansen, H; Sijbrands, EJG

    2006-01-01

    Aims/hypothesis: Variation in the human apolipoprotein (APO) A5 gene (APOA5) is associated with elevated plasma triglycerides. However, data on the exact role of plasma concentrations of APOA5 in human triglyceride homeostasis are lacking. In the present study, we estimated plasma APOA5 levels in pa

  18. [Lipases in catalytic reactions of organic chemistry].

    Bezborodov, A M; Zagustina, N A

    2014-01-01

    Aspects of enzymatic catalysis in lipase-catalyzed reactions of organic synthesis are discussed in the review. The data on modern methods of protein engineering and enzyme modification allowing a broader range of used substrates are briefly summarized. The application of lipase in the preparation of pharmaceuticals and agrochemicals containing no inactive enantiomers and in the synthesis of secondary alcohol enantiomers and optically active amides is demonstrated. The subject of lipase involvement in the C-C bond formation in the Michael reaction is discussed. Data on the enzymatic synthesis of construction materials--polyesters, siloxanes, etc.--are presented. Examples demonstrating the application of lipase enzymatic catalysis in industry are given. PMID:25707112

  19. [Water binding of adsorptive immobilized lipases].

    Loose, S; Meusel, D; Muschter, A; Ruthe, B

    1990-01-01

    It is supposed that not only the total water content of lipase preparations but more their state of water binding is of technological importance in enzymatic interesterification reactions in systems nearly free from water. The isotherms at 65 degrees C of two microbial lipases immobilized on various adsorbents as well as different adsorbents themselves are shown. The water binding capacity in the range of water content of technological interest decreases from the anion exchange resin Amberlyst A 21 via nonpolar adsorbent Amberlite XAD-2 to kieselguhr Celite 545. It is demonstrated that water binding by lipases is depending on temperature but is also affected by adsorptive immobilization. Adsorptive immobilized lipases show hysteresis, which is very important for preparing a definite water content of the enzyme preparations. PMID:2325750

  20. Utilization of immobilized lipases as catalysts in the transesterification of non-edible vegetable oils with ethanol

    P. C. Tiosso

    2014-12-01

    Full Text Available This work reports the use of commercially available immobilized lipase preparations (Novozym® 435 and Lipozyme TL IM, both from Novozymes, and Lipase PS IM from Amano as catalysts in the transesterification reaction of different alkyl-chain triglycerides with ethanol. The ethanolysis of native oils from Brazilian Amazon plants andiroba (Carapa guianensis, babassu (Orbignya sp., jatropa (Jatropha curcas, and palm (Elaeis sp. was studied in a solvent-free system. In a typical reaction, the immobilized preparations were added to the mixture of vegetable oil-to-ethanol in a molar ratio of 1:9. The reactions were performed at 50 ºC for a maximum period of 48 h. Under the conditions used, all the immobilized lipase preparations were able to generate the main esters of fatty acids present in the tested feedstocks, and both the reaction rate and ester yield were dependent on the source of lipase and vegetable oil. The viscosity values for the samples obtained in each reaction displayed a consistent reduction in relation to their original feedstocks, which also confirms the high conversion of triglycerides to ethyl esters (99.8-74.0%. The best performances were obtained with Amano PS IM and Novozym® 435, with the biodiesel samples from the babassu and jatropha oils exhibiting viscosity values in accordance with those predicted by the technical standards of ASTM D6751 (1.9-6.0 mm²/s. Lipozyme TL IM displayed an unsatisfactory performance, indicating that the conditions of the transesterification reaction should be improved. This comparative study using different catalysts and several vegetable oil sources with varying fatty acid compositions is particularly important for all tropical countries with a diversity of native vegetable oil sources.

  1. Mechanosensation in an adipose fin.

    Aiello, Brett R; Stewart, Thomas A; Hale, Melina E

    2016-03-16

    Adipose fins are found on approximately 20% of ray-finned fish species. The apparently rudimentary anatomy of adipose fins inspired a longstanding hypothesis that these fins are vestigial and lack function. However, adipose fins have evolved repeatedly within Teleostei, suggesting adaptive function. Recently, adipose fins were proposed to function as mechanosensors, detecting fluid flow anterior to the caudal fin. Here we test the hypothesis that adipose fins are mechanosensitive in the catfish Corydoras aeneus. Neural activity, recorded from nerves that innervate the fin, was shown to encode information on both movement and position of the fin membrane, including the magnitude of fin membrane displacement. Thus, the adipose fin of C. aeneus is mechanosensitive and has the capacity to function as a 'precaudal flow sensor'. These data force re-evaluation of adipose fin clipping, a common strategy for tagging fishes, and inform hypotheses of how function evolves in novel vertebrate appendages. PMID:26984621

  2. α-Tocopherol adipose tissue stores are depleted after burn injury in pediatric patients123

    Leonard, Scott W; Traber, Daniel L; Traber, Lillian D; Gallagher, James; Bobe, Gerd; Jeschke, Marc G; Finnerty, Celeste C; Herndon, David

    2010-01-01

    Background: We previously showed that thermal injury depletes plasma vitamin E in pediatric burn patients; however, plasma changes may reflect immediate alterations in vitamin E nutriture. Adipose tissue α-tocopherol concentrations are generally accepted to reflect long-term vitamin E status. Objective: To test the hypothesis that thermal injury depletes body stores of vitamin E, α-tocopherol concentrations were measured in adipose tissue samples. Design: Pediatric patients (n = 8) were followed up to 1 y after burn injury. Surgically obtained samples were collected at various intervals and stored at −80°C in a biorepository. α- and γ-Tocopherols, cholesterol, and triglycerides were measured in the same tissue aliquot. Results: During the first week after injury, adipose tissue α-tocopherol concentrations were within the expected normal range of 199 ± 40 nmol/g adipose tissue but were substantially lower at weeks 2 and 3 (133 ± 13 and 109 ± 8 nmol/g adipose tissue, respectively). Individual rates of decrease, estimated by linear regression, showed that adipose tissue α-tocopherol decreased by an average of 6.1 ± 0.6 nmol/g daily. During the first month after injury, adipose tissue triglyceride concentrations also decreased, whereas no changes in cholesterol concentrations occurred. Conclusions: These data emphasize that the burn injury experienced by these pediatric patients altered their metabolism such that vitamin E status diminished during the month after injury. Further studies are needed to evaluate the mechanism and consequences of the observed vitamin E depletion. This trial was registered at clinicaltrials.gov as NCT00675714. PMID:20881067

  3. Structure and Function of Lipase

    Skjold-Jørgensen, Jakob

    towards an open conformation enabling the substrate to gain access, thus initiating catalysis.Lipases have been studied for decades and their functional features have drawn much attention withinindustrial applications since their first discovery. However, given that their molecular action takes placeat...... a function of solvent polarity,which showed pronounced differences in open vs. closed states of the lid between TlL and the lidvariants.To elucidate whether the observed differences in activation could be ascribed to a lowering ofthe energy barrier of lid-opening, molecular dynamic simulations were...... carried out to calculate the energydifference between the open and closed lid conformation for TlL and a selection of lid-variants (PaperIII). Here, a correlation between experimental and theoretical data was discovered supporting the notionlid plays a key role in governing activation at the interface...

  4. Pancreatic Lipase Inhibitory Effects of Mangosteen Pericarps

    Xinjie Lin; Baojun Xu; Liu Rui

    2014-01-01

    Pancreatic lipase plays a key role in the digestion and absorption of lipids, inhibition of Pancreatic Lipase (PL) is considered as a new approach to obesity treatment. The objective of the present study was to find PL inhibitors from natural food sources. Eighteen natural food products sampled from local supermarkets in Zhuhai were tested for PL inhibitory activity using a copper-soap photometric method. Among the samples tested, the crude extracts from mangosteen pericarp, lemon pulp, celer...

  5. The lipase system of Yarrowia lipolytica

    Choupina, Altino; Gonzalez, Francisco J.; Morín, M.; Burguillo, Francisco J.; Ferminan, E.; Dominguez, Ángel

    1999-01-01

    Among yeast species, Yarrowia lipolytica is one of the highest producers of extracellular proteins ( acid, neutral and alkaline proteases, ácid phosphatase, ribonucleases and lipases). Lipases ( triacylglycerol hydrolases) are important enzymes in fat metabolism, catalyzing the breakdown of triacilglycerols to free fatty acids and glycerol. Owing to the very low solubility of ther natural substrats, this hydrolysis is catalysed at the interfase beteween an insoluble substrat and the aqueous p...

  6. Olive Oil as Inductor of Microbial Lipase

    Zarevúcka, Marie

    Rijeka : InTech, 2012 - (Dimitrios, B.), s. 457-470 ISBN 978-953-307-921-9 R&D Projects: GA ČR GAP502/10/1734 Institutional research plan: CEZ:AV0Z40550506 Keywords : olive oil * microorganism * lipase Subject RIV: CC - Organic Chemistry http://www.intechopen.com/books/ olive -oil-constituents-quality-health-properties-and-bioconversions/ olive -oil-as-inductor-of-microbial-lipase

  7. Subcutaneous adipose tissue classification

    A. Sbarbati

    2010-11-01

    Full Text Available The developments in the technologies based on the use of autologous adipose tissue attracted attention to minor depots as possible sampling areas. Some of those depots have never been studied in detail. The present study was performed on subcutaneous adipose depots sampled in different areas with the aim of explaining their morphology, particularly as far as regards stem niches. The results demonstrated that three different types of white adipose tissue (WAT can be differentiated on the basis of structural and ultrastructural features: deposit WAT (dWAT, structural WAT (sWAT and fibrous WAT (fWAT. dWAT can be found essentially in large fatty depots in the abdominal area (periumbilical. In the dWAT, cells are tightly packed and linked by a weak net of isolated collagen fibers. Collagenic components are very poor, cells are large and few blood vessels are present. The deep portion appears more fibrous then the superficial one. The microcirculation is formed by thin walled capillaries with rare stem niches. Reinforcement pericyte elements are rarely evident. The sWAT is more stromal; it is located in some areas in the limbs and in the hips. The stroma is fairly well represented, with a good vascularity and adequate staminality. Cells are wrapped by a basket of collagen fibers. The fatty depots of the knees and of the trochanteric areas have quite loose meshes. The fWAT has a noteworthy fibrous component and can be found in areas where a severe mechanic stress occurs. Adipocytes have an individual thick fibrous shell. In conclusion, the present study demonstrates evident differences among subcutaneous WAT deposits, thus suggesting that in regenerative procedures based on autologous adipose tissues the sampling area should not be randomly chosen, but it should be oriented by evidence based evaluations. The structural peculiarities of the sWAT, and particularly of its microcirculation, suggest that it could represent a privileged source for

  8. Structural characterization of MAPLE deposited lipase biofilm

    Aronne, Antonio [Department of Chemical Engineering, Materials and Industrial Production, Università degli Studi di Napoli Federico II, Piazzale V. Tecchio 80, 80125 Napoli (Italy); Ausanio, Giovanni; Bloisi, Francesco [CNR-SPIN and Department of Physics, Università degli Studi di Napoli Federico II, Piazzale V. Tecchio 80, 80125 Napoli (Italy); Calabria, Raffaela [Istituto Motori-CNR, via G. Marconi 8, 80125 Napoli (Italy); Califano, Valeria, E-mail: v.califano@im.cnr.it [Istituto Motori-CNR, via G. Marconi 8, 80125 Napoli (Italy); Fanelli, Esther [Department of Chemical Engineering, Materials and Industrial Production, Università degli Studi di Napoli Federico II, Piazzale V. Tecchio 80, 80125 Napoli (Italy); Massoli, Patrizio [Istituto Motori-CNR, via G. Marconi 8, 80125 Napoli (Italy); Vicari, Luciano R.M. [CNR-SPIN and Department of Physics, Università degli Studi di Napoli Federico II, Piazzale V. Tecchio 80, 80125 Napoli (Italy)

    2014-11-30

    Highlights: • Lipase from Candida Rugosa was deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) on KBr pellets, mica and glass substrate. • The deposited film was characterized morphologically and structurally by optical microscopy, SEM and FTIR analysis. • Results of characterization underlined a phenomenon of aggregation taking place. • The aggregation phenomenon was reversible since lipase showed activity in the transesterification reaction between soybean oil and isopropyl alcohol once detached from the substrate. - Abstract: Lipases (triacylglycerol ester hydrolases) are enzymes used in several industrial applications. Enzymes immobilization can be used to address key issues limiting widespread application at industrial level. Immobilization efficiency is related to the ability to preserve the native conformation of the enzyme. MAPLE (Matrix Assisted Pulsed Laser Evaporation) technique, a laser deposition procedure for treating organic/polymeric/biomaterials, was applied for the deposition of lipase enzyme in an ice matrix, using near infrared laser radiation. Microscopy analysis showed that the deposition occurred in micrometric and submicrometric clusters with a wide size distribution. AFM imaging showed that inter-cluster regions are uniformly covered with smaller aggregates of nanometric size. Fourier transform infrared spectroscopy was used for both recognizing the deposited material and analyzing its secondary structure. Results showed that the protein underwent reversible self-association during the deposition process. Actually, preliminary tests of MAPLE deposited lipase used for soybean oil transesterification with isopropyl alcohol followed by gas chromatography–mass spectrometry gave results consistent with undamaged deposition of lipase.

  9. Structural characterization of MAPLE deposited lipase biofilm

    Highlights: • Lipase from Candida Rugosa was deposited by Matrix Assisted Pulsed Laser Evaporation (MAPLE) on KBr pellets, mica and glass substrate. • The deposited film was characterized morphologically and structurally by optical microscopy, SEM and FTIR analysis. • Results of characterization underlined a phenomenon of aggregation taking place. • The aggregation phenomenon was reversible since lipase showed activity in the transesterification reaction between soybean oil and isopropyl alcohol once detached from the substrate. - Abstract: Lipases (triacylglycerol ester hydrolases) are enzymes used in several industrial applications. Enzymes immobilization can be used to address key issues limiting widespread application at industrial level. Immobilization efficiency is related to the ability to preserve the native conformation of the enzyme. MAPLE (Matrix Assisted Pulsed Laser Evaporation) technique, a laser deposition procedure for treating organic/polymeric/biomaterials, was applied for the deposition of lipase enzyme in an ice matrix, using near infrared laser radiation. Microscopy analysis showed that the deposition occurred in micrometric and submicrometric clusters with a wide size distribution. AFM imaging showed that inter-cluster regions are uniformly covered with smaller aggregates of nanometric size. Fourier transform infrared spectroscopy was used for both recognizing the deposited material and analyzing its secondary structure. Results showed that the protein underwent reversible self-association during the deposition process. Actually, preliminary tests of MAPLE deposited lipase used for soybean oil transesterification with isopropyl alcohol followed by gas chromatography–mass spectrometry gave results consistent with undamaged deposition of lipase

  10. LIPASES PRODUCED BY YEASTS: POWERFUL BIOCATALYSTS FOR INDUSTRIAL PURPOSES

    Luiza Lux Lock

    2007-12-01

    Full Text Available The term “lipolytic enzymes” refers to the lipases and carboxylic ester hydrolases. Lipase production is widespread among yeasts, butfew are capable of producing lipases with interesting characteristics and in sufficient amounts to be industrially useful. The literatureconcerning lipases produced by Candida rugosa, Yarrowia (Candida lipolytica, Candida antarctica and other emerging lipaseproducingyeasts is reviewed. The use of recombinant lipases is discussed, with emphasis on the utilization of heterologous expressionsystems and design of chimeras. Finally, the three approaches that aim the improvement of lipase production or the modification of thesubstrate selectivity of the enzyme (medium engineering, biocatalyst engineering, and protein engineering are discussed.

  11. Lipidomic Profiling of Adipose Tissue Reveals an Inflammatory Signature in Cancer-Related and Primary Lymphedema

    Sedger, Lisa M.; Tull, Dedreia L.; Malcolm J McConville; De Souza, David P.; Rupasinghe, Thusitha W. T.; Williams, Spencer J; Saravanan Dayalan; Daniel Lanzer; Helen Mackie; Lam, Thomas C.; John Boyages

    2016-01-01

    Cancer-related and primary lymphedema (LE) are associated with the production of adipose tissue (AT). Nothing is known, however, about the lipid-based molecules that comprise LE AT. We therefore analyzed lipid molecules in lipoaspirates and serum obtained from LE patients, and compared them to lipoaspirates from cosmetic surgery patients and healthy control cohort serum. LE patient serum analysis demonstrated that triglycerides, HDL- and LDL-cholesterol and lipid transport molecules remained ...

  12. Adipose Tissue Fatty Acid Storage Factors: Effects of Depot, Sex and Fat Cell Size

    Hames, Kazanna C.; Koutsari, Christina; Santosa, Sylvia; Bush, Nikki C.; Jensen, Michael D.

    2015-01-01

    Background/Objectives Patterns of postabsorptive adipose tissue fatty acid storage correlate with sex-specific body fat distribution. Some proteins and enzymes participating in this pathway include CD36 (facilitated transport), acyl-CoA synthetases (ACS; the first step in fat metabolism), and diacylglycerol acetyl-transferase (DGAT; the final step of triglyceride synthesis). Our goal was to better define CD36, ACS and DGAT in relation to sex, subcutaneous fat depots, and adipocyte size. Subje...

  13. BMP7 Activates Brown Adipose Tissue and Reduces Diet-Induced Obesity Only at Subthermoneutrality

    Boon, M.R.; Berg, S.A.A. van den; Wang, Y; Bossche, J. van den; Karkampouna, S.; Bauwens, M.; Saint-Hubert, M. de; Horst, G; Vukicevic, S.; de Winther, M. P. J.; Havekes, L M; Jukema, J.W.; Tamsma, J. T.; Pluijm, G. van der; van Dijk, K W

    2013-01-01

    Background/Aims:Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone Morphogenetic Protein 7 (BMP7) was identified as an inducer of BAT differentiation. We aimed to elucidate the role of sympathetic activation in the effect of BMP7...

  14. Parathyroid hormone is not an inhibitor of lipoprotein lipase activity.

    Arnadottir, M; Nilsson-Ehle, P

    1994-01-01

    The reduced lipoprotein lipase (LPL) activities in uraemia are reflected by increased serum triglyceride concentrations and reduced HDL cholesterol concentrations. Both hyperparathyroidism and circulating inhibitor(s) of LPL have been associated with the disturbances of lipid metabolism in uraemia. The aim of the present study was to investigate if parathyroid hormone (PTH) had an inhibitory effect on LPL activity. Plasma post-heparin LPL activities, plasma LPL inhibitory activities, serum PTHintact and serum PTHC-terminal concentrations were analysed in 20 patients on haemodialysis and 20 healthy controls. The effects of purified, human PTHintact and a carboxyterminal fragment of PTH (PTH39-84) on LPL activities in post-heparin plasma from healthy individuals and on the enzyme activity of purified, bovine milk LPL, activated with apolipoprotein CII, were studied. Patients had significantly higher plasma LPL inhibitory activities than controls, but there was no correlation between plasma LPL inhibitory activities and serum PTH concentrations. Neither PTHintact nor PTH39-84 had a significant effect on LPL activities in vitro. Thus there was no evidence of a direct inhibition of LPL activity by PTH under the present in-vivo or in-vitro conditions. PMID:7870347

  15. Chylous ascites secondary to hyperlipidemic pancreatitis with normal serum amylase and lipase

    Fahmi Yousef Khan; Tssa Matar

    2007-01-01

    A 54-year old man with a family history of hyperlipidemia was admitted with a 12 h history of severe generalized abdominal pain associated with nausea, vomiting and abdominal distension. Examination of the abdomen revealed tenderness in the periumblical area with shifting dullness. Serum pancreatic amylase was 29 IU/L and lipase 44 IU/L, triglyceride 36.28 mmol/L. Ultrasound showed ascites. CT of the abdomen with contrast showed inflammatory changes surrounding the pancreas consistent with acute pancreatitis. Ultrasound (US)guided abdomen paracentesis yielded a milky fluid with high triglyceride content consistent with chylous ascites.The patient was kept fasting and intravenous fluid hydration was provided. Meperidine was administered for pain relief. On the following days the patient's condition improved and he was gradually restarted on a low-fat diet, and fat lowering agent (gemfibrozil) was begun,600 mg twice a day. On d 14, abdomen US was repeated and showed fluid free peritoneal cavity. The patient was discharged after 18 d of hospitalization with 600 mg gemfibrozil twice a day. At the time of discharge, the fasting triglyceride was 4.2 mmol/L. After four weeks the patient was seen in the clinic, he was well.

  16. Application of a Burkholderia cepacia lipase-immobilized silica monolith to batch and continuous biodiesel production with a stoichiometric mixture of methanol and crude Jatropha oil

    Takahashi Ryo

    2011-10-01

    Full Text Available Abstract Background The enzymatic production of biodiesel through alcoholysis of triglycerides has become more attractive because it shows potential in overcoming the drawbacks of chemical processes. In this study, we investigate the production of biodiesel from crude, non-edible Jatropha oil and methanol to characterize Burkholderia cepacia lipase immobilized in an n-butyl-substituted hydrophobic silica monolith. We also evaluate the performance of a lipase-immobilized silica monolith bioreactor in the continuous production of biodiesel. Results The Jatropha oil used contained 18% free fatty acids, which is problematic in a base-catalyzed process. In the lipase-catalyzed reaction, the presence of free fatty acids made the reaction mixture homogeneous and allowed bioconversion to proceed to 90% biodiesel yield after a 12 hour reaction time. The optimal molar ratio of methanol to oil was 3.3 to 3.5 parts methanol to one part oil, with water content of 0.6% (w/w. Further experiments revealed that B. cepacia lipase immobilized in hydrophobic silicates was sufficiently tolerant to methanol, and glycerol adsorbed on the support disturbed the reaction to some extent in the present reaction system. The continuous production of biodiesel was performed at steady state using a lipase-immobilized silica monolith bioreactor loaded with 1.67 g of lipase. The yield of 95% was reached at a flow rate of 0.6 mL/h, although the performance of the continuous bioreactor was somewhat below that predicted from the batch reactor. The bioreactor was operated successfully for almost 50 days with 80% retention of the initial yield. Conclusions The presence of free fatty acids originally contained in Jatropha oil improved the reaction efficiency of the biodiesel production. A combination of B. cepacia lipase and its immobilization support, n-butyl-substituted silica monolith, was effective in the production of biodiesel. This procedure is easily applicable to the design

  17. Independent Stem Cell Lineages Regulate Adipose Organogenesis and Adipose Homeostasis

    Yuwei Jiang

    2014-11-01

    Full Text Available Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult progenitors are specified during the developmental period and express PPARγ, they have distinct microanatomical, functional, morphogenetic, and molecular profiles. Furthermore, the two compartments derive from different lineages; whereas adult adipose progenitors fate-map from an SMA+ mural lineage, developmental progenitors do not. Remarkably, the adult progenitor compartment appears to be specified earlier than the developmental cells and then enters the already developmentally formed adipose depots. Thus, two distinct cell compartments control adipose organ development and organ homeostasis, which may provide a discrete therapeutic target for childhood and adult obesity.

  18. Transcriptional regulation of adipocyte hormone-sensitive lipase by glucose.

    Smih, Fatima; Rouet, Philippe; Lucas, Stéphanie; Mairal, Aline; Sengenes, Coralie; Lafontan, Max; Vaulont, Sophie; Casado, Marta; Langin, Dominique

    2002-02-01

    Hormone-sensitive lipase (HSL) catalyzes the rate-limiting step in the mobilization of fatty acids from adipose tissue, thus determining the supply of energy substrates in the body. HSL mRNA was positively regulated by glucose in human adipocytes. Pools of stably transfected 3T3-F442A adipocytes were generated with human adipocyte HSL promoter fragments from -2,400/+38 to -31/+38 bp linked to the luciferase gene. A glucose-responsive region was mapped within the proximal promoter (-137 bp). Electromobility shift assays showed that upstream stimulatory factor (USF)-1 and USF2 and Sp1 and Sp3 bound to a consensus E-box and two GC-boxes in the -137-bp region. Cotransfection of the -137/+38 construct with USF1 and USF2 expression vectors produced enhanced luciferase activity. Moreover, HSL mRNA levels were decreased in USF1- and USF2-deficient mice. Site-directed mutagenesis of the HSL promoter showed that the GC-boxes, although contributing to basal promoter activity, were dispensable for glucose responsiveness. Mutation of the E-box led to decreased promoter activity and suppression of the glucose response. Analogs and metabolites were used to determine the signal metabolite of the glucose response. The signal is generated downstream of glucose-6-phosphate in the glycolytic pathway before the triose phosphate step. PMID:11812735

  19. Triacylglycerol kinetics in endotoxic rats with suppressed lipoprotein lipase activity

    Bagby, G.J.; Corll, C.B.; Martinez, R.R.

    1987-07-01

    Hypertriglyceridemia observed in animals after bacterial endotoxin administration and some forms of sepsis can result from increased hepatic triacylglycerol (TG) output or decreased TG clearance by extrahepatic tissues. To differentiate between these two possibilities, TG and free fatty acid (FFA) kinetics were determined in control and endotoxin-injected rats 18 h after treatment. Plasma TG and FFA kinetics were assessed by a constant intravenous infusion with (9,10-/sup 3/H)palmitate-labeled very low-density lipoprotein and (1-/sup 14/C)palmitate bound to albumin, respectively. In addition, lipoprotein lipase (LPL) activity was determined in heart, skeletal muscle, and adipose tissue as well as in postheparin plasma of functionally hepatectomized, adrenalectomized, and gonadectomized rats. Plasma FFA acid concentrations were slightly increased in endotoxin-treated rats but their turnover did not differ from control. Endotoxin-treated rats had a threefold increase in plasma TG concentrations and decreased heart, skeletal muscle, and post-heparin plasma LPL activity. Plasma TG turnover was decreased, indicating that hypertriglyceridemia was not due to an increased TG output by the liver. Instead, the endotoxin-induced increase in plasma TG concentration was consequence of the 80% reduction in TG metabolic clearance rate. Thus, suppression of LPL activity in endotoxic animals impairs TG clearance resulting in hypertriglyceridemia. Furthermore, endotoxin administration reduced the delivery of TG-FFA to extrahepatic tissues because hepatic synthesis and secretion of TG from plasma FFA was decreased and LPL activity was suppressed.

  20. Expression of Resistin Protein in Normal Human Subcutaneous Adipose Tissue and Pregnant Women Subcutaneous Adipose Tissue and Placenta

    ZHOU Yongming; GUO Tiecheng; ZHANG Muxun; GUO Wei; YU Meixia; XUE Keying; HUANG Shiang; CHEN Yanhong; ZHU Huanli; XU Lijun

    2006-01-01

    The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta and the relationship between obesity, type 2 diabetes mellitus (T2DM), pregnant physiological insulin resistance (IR) and gestational diabetes mellitus (GDM) was investigated. The expression of resistin protein in normal human abdominal, thigh, pregnant women abdominal, non-pregnant women abdominal subcutaneous adipose tissue and placenta was detected by using Western blotting method.Fasting serum glucose concentration was measured by glucose oxidase assay. Serum cholesterol (CHOL), serum triglycerides (TG), serum HDL cholesterol (HDL-C) and serum LDL cholesterol (LDL-C) were determined by full automatic biochemical instrument. Fasting insulin was measured by enzyme immunoassay to calculate insulin resistance index (IRI). Height, weight, systolic blood pressure (SBP) and diastolic blood pressure (DBP) were measured to calculate body mass index (BMI) and body fat percentage (BF %). Resistin protein expression in pregnant women placental tissue (67 905±8441) (arbitrary A values) was much higher than that in subcutaneous adipose tissue in pregnant women abdomen (40 718 ± 3818, P < 0.01), non-pregnant women abdomen (38 288±2084, P<0.01), normal human abdomen (39 421±6087, P<0.01)and thigh (14 942 ±6706, P<0. 001) respectively. The resistin expression in abdominal subcutaneous adipose tissue showed no significant difference among pregnant, non-pregnant women and normal human, but much higher than that in thigh subcutaneous adipose tissue (P<0. 001). Pearson analysis revealed that resistin protein was correlated with BMI (r=0.42), fasting insulin concentration (r=0.38),IRI (r=0. 34), BF % (r=0.43) and fasting glucose (r=0. 39), but not with blood pressure,CHOL, TG, HDL-C and LDL-C. It was suggested that resistin protein expression in human abdominal subcutaneous adipose tissue was much higher

  1. Independent Stem Cell Lineages Regulate Adipose Organogenesis and Adipose Homeostasis

    Yuwei Jiang; Daniel C. Berry; Wei Tang; Jonathan M. Graff

    2014-01-01

    Adipose tissues have striking plasticity, highlighted by childhood and adult obesity. Using adipose lineage analyses, smooth muscle actin (SMA)-mural cell-fate mapping, and conditional PPARγ deletion to block adipocyte differentiation, we find two phases of adipocyte generation that emanate from two independent adipose progenitor compartments: developmental and adult. These two compartments are sequentially required for organ formation and maintenance. Although both developmental and adult pr...

  2. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue.

    Luana Amorim Biondo

    Full Text Available White adipose tissue (WAT plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc and adipogenic factors (Pparg, C/ebpa, and Srebp1c in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects.

  3. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue

    Cruz, Maysa Mariana; Cunha, Roberta D. C.; Alonso-Vale, Maria Isabel; Oyama, Lila Missae; Nascimento, Claudia M. Oller; Pimentel, Gustavo Duarte; dos Santos, Ronaldo V. T.; Lira, Fabio Santos

    2016-01-01

    White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects. PMID:27015538

  4. Impact of Doxorubicin Treatment on the Physiological Functions of White Adipose Tissue.

    Biondo, Luana Amorim; Lima Junior, Edson Alves; Souza, Camila Oliveira; Cruz, Maysa Mariana; Cunha, Roberta D C; Alonso-Vale, Maria Isabel; Oyama, Lila Missae; Nascimento, Claudia M Oller; Pimentel, Gustavo Duarte; Dos Santos, Ronaldo V T; Lira, Fabio Santos; Rosa Neto, José Cesar

    2016-01-01

    White adipose tissue (WAT) plays a fundamental role in maintaining energy balance and important endocrine functions. The loss of WAT modifies adipokine secretion and disrupts homeostasis, potentially leading to severe metabolic effects and a reduced quality of life. Doxorubicin is a chemotherapeutic agent used clinically because of its good effectiveness against various types of cancer. However, doxorubicin has deleterious effects in many healthy tissues, including WAT, liver, and skeletal and cardiac muscles. Our objective was to investigate the effects of doxorubicin on white adipocytes through in vivo and in vitro experiments. Doxorubicin reduced the uptake of glucose by retroperitoneal adipocytes and 3T3-L1 cells via the inhibition of AMP-activated protein kinase Thr172 phosphorylation and glucose transporter 4 content. Doxorubicin also reduced the serum level of adiponectin and, to a greater extent, the expression of genes encoding lipogenic (Fas and Acc) and adipogenic factors (Pparg, C/ebpa, and Srebp1c) in retroperitoneal adipose tissue. In addition, doxorubicin inhibited both lipogenesis and lipolysis and reduced the hormone-sensitive lipase and adipose tissue triacylglycerol lipase protein levels. Therefore, our results demonstrate the impact of doxorubicin on WAT. These results are important to understand some side effects observed in patients receiving chemotherapy and should encourage new adjuvant treatments that aim to inhibit these side effects. PMID:27015538

  5. ApoC-III inhibits clearance of triglyceride-rich lipoproteins through LDL family receptors.

    Gordts, Philip L S M; Nock, Ryan; Son, Ni-Huiping; Ramms, Bastian; Lew, Irene; Gonzales, Jon C; Thacker, Bryan E; Basu, Debapriya; Lee, Richard G; Mullick, Adam E; Graham, Mark J; Goldberg, Ira J; Crooke, Rosanne M; Witztum, Joseph L; Esko, Jeffrey D

    2016-08-01

    Hypertriglyceridemia is an independent risk factor for cardiovascular disease, and plasma triglycerides (TGs) correlate strongly with plasma apolipoprotein C-III (ApoC-III) levels. Antisense oligonucleotides (ASOs) for ApoC-III reduce plasma TGs in primates and mice, but the underlying mechanism of action remains controversial. We determined that a murine-specific ApoC-III-targeting ASO reduces fasting TG levels through a mechanism that is dependent on low-density lipoprotein receptors (LDLRs) and LDLR-related protein 1 (LRP1). ApoC-III ASO treatment lowered plasma TGs in mice lacking lipoprotein lipase (LPL), hepatic heparan sulfate proteoglycan (HSPG) receptors, LDLR, or LRP1 and in animals with combined deletion of the genes encoding HSPG receptors and LDLRs or LRP1. However, the ApoC-III ASO did not lower TG levels in mice lacking both LDLR and LRP1. LDLR and LRP1 were also required for ApoC-III ASO-induced reduction of plasma TGs in mice fed a high-fat diet, in postprandial clearance studies, and when ApoC-III-rich or ApoC-III-depleted lipoproteins were injected into mice. ASO reduction of ApoC-III had no effect on VLDL secretion, heparin-induced TG reduction, or uptake of lipids into heart and skeletal muscle. Our data indicate that ApoC-III inhibits turnover of TG-rich lipoproteins primarily through a hepatic clearance mechanism mediated by the LDLR/LRP1 axis. PMID:27400128

  6. Relationship of adipocyte size with adiposity and metabolic risk factors in Asian Indians.

    Ved Prakash Meena

    Full Text Available Enlargement of adipocyte is associated with their dysfunction and alterations in metabolic functions.We evaluated the association of adipocyte size of subcutaneous and omental adipose tissue with body composition and cardiovascular risk factors in Asian Indians.Eighty (40 males and 40 females non-diabetic adult subjects undergoing elective abdominal surgery were included. Pre-surgery evaluation included anthropometric measurements, % body fat by bioimpedance, abdominal fat area at L2-3 level (computed tomography and biochemical investigations (fasting blood glucose and insulin, lipids and hsCRP. During surgery, about 5 grams each of omental and subcutaneous adipose tissue was obtained for adipocyte size determination.Females had higher BMI, % body fat, skinfold thickness, total and subcutaneous abdominal fat area as compared to males. Overweight was present in 42.5% and 67.5%, and abdominal obesity in 5% and 52.5% males and females, respectively. Subcutaneous adipocyte size was significantly higher than omental adipocyte size. Omental adipocyte size correlated more strongly than subcutaneous adipocyte size with measures of adiposity (BMI, waist circumference, %BF, total and subcutaneous abdominal fat area and biochemical measures (fasting glucose, total cholesterol, triglycerides and HOMA-IR, the correlations being stronger in females. The correlation of adipocyte size with metabolic parameters was attenuated after adjusting for measures of adiposity.Omental adipocyte size, though smaller than the subcutaneous adipocyte size, was more closely related to measures of adiposity and metabolic parameters. However, the relationship was not independent of measures of adiposity.

  7. Lipoprotein lipase: size of the functional unit determined by radiation inactivation

    Radiation inactivation was used to determine the functional molecular weight of lipoprotein lipase (LPL) in rat heart and adipose tissues. This technique reveals the size of the smallest unit required to carry out the enzyme function. Supernatant fractions of the tissue homogenates were exposed to high energy electrons at -135 degrees C. LPL activity showed a simple exponential decay in all samples tested. Because changes in nutritional state shift the distribution of LPL between the capillary endothelial and parenchymal cells within heart and adipose tissues, fasted and refed rats were used for the radiation studies. The functional molecular weight was calculated to be 127,000 +/- 15,000 (mean +/- SD) daltons for heart and adipose. Thus, the smallest unit required for enzyme function was the same in both of these tissues and did not vary with nutritional state. The data suggest that, compared with LPL monomer sizes reported in the range 55,000 to 72,000, this active unit constitutes a dimer

  8. Effects of sucrose, caffeine, and cola beverages on obesity, cold resistance, and adipose tissue cellularity.

    Bukowiecki, L J; Lupien, J; Folléa, N; Jahjah, L

    1983-04-01

    Rats consuming Coca-Cola and Purina chow ad libitum increased their total energy intake by 50% without excess weight gain. Their resistance to cold was markedly improved. These phenomena were characterized by significant increases in interscapular brown adipose tissue weight (IBAT) (91%), cellularity (59%), triglyceride content (52%), protein content (94%), and cytochrome oxidase activity (167%). In contrast, Coca-Cola consumption did not significantly affect the cellularity or triglyceride content of parametrial white adipose tissue (PWAT), although it slightly augmented PWAT weight. The effects of Coca-Cola on cold resistance, IBAT cellularity, and composition were entirely reproduced by sucrose, but not caffeine, consumption. Although caffeine also increased IBAT cellularity and composition, it significantly decreased the rate of body weight gain, PWAT weight, and adipocyte size. Moreover, it markedly inhibited adipocyte proliferation in PWAT thereby mimicking the effects of exercise training and food restriction (Bukowiecki et al., Am. J. Physiol. 239 (Endocrinol. Metab. 2): E422-E429, 1980). It is concluded a) that sucrose and Coca-Cola consumption improve the resistance of rats to cold, most probably by increasing brown adipose tissue cellularity, and b) that moderate caffeine intake might be useful for inhibiting proliferative activity in white adipose tissue, thereby preventing obesity. PMID:6837766

  9. Glucose-dependent insulinotropic polypeptide has impaired effect on abdominal, subcutaneous adipose tissue metabolism in obese subjects

    Asmar, M; Simonsen, L; Arngrim, N;

    2013-01-01

    that increased GIP secretion in obesity will promote lipid deposition in adipose tissue. In light of the current attempts to employ GIP antagonists in the treatment and prevention of human obesity, the present experiments were performed in order to elucidate whether the adipose tissue lipid metabolism...... would be enhanced or blunted during a GIP, hyperinsulinemic and hyperglycemic (HI-HG) clamp in obese subjects with either normal glucose tolerance (NGT) or impaired glucose tolerance (IGT). DESIGN: Sixteen obese (BMI>30 kg m(-2)) subjects were divided into two groups, based on their plasma glucose...... deposition in adipose tissue under the applied experimental conditions and likewise the circulating triglyceride (TAG) concentrations remained constant. CONCLUSION: The applied GIP, HI-HG clamp did not induce any changes in TAG uptake in adipose tissue in obese subjects. This may be due to a blunted increase...

  10. Modification of pancreatic lipase properties by directed molecular evolution

    Colin, Damien; Deprez, Paule; Silva, Noella; Infantes, Lourdes; Kerfelec, Brigitte

    2010-01-01

    Cystic fibrosis is associated with pancreatic insufficiency and acidic intraluminal conditions that limit the action of pancreatic enzyme replacement therapy, especially that of lipase. Directed evolution combined with rational design was used in the aim of improving the performances of the human pancreatic lipase at acidic pH. We set up a method for screening thousands of lipase variants for activity at low pH. A single round of random mutagenesis yielded one lipase variant with an activity ...

  11. Isolated co-lipase deficiency in two brothers.

    Hildebrand, H; Borgström, B.; Békássy, A; Erlanson-Albertsson, C; Helin, I

    1982-01-01

    Two normally developed Assyrian brothers with isolated pancreatic co-lipase deficiency are described. They presented at the age of 5-6 years with loose stools. They had steatorrhoea, and analysis of exocrine pancreatic enzymes in the small intestine showed co-lipase deficiency, while amylase, chymotrypsin, trypsin and lipase were normal. Intraduodenal infusion of purified co-lipase improved fat digestion measured by the triolein breath test. Their steatorrhoea diminished on treatment with ent...

  12. Efficient biocatalyst by encapsulating lipase into nanoporous gold

    Du, Xiaoyu; Liu, Xueying; Li, Yufei; Wu, Chao; Wang, Xia; Xu, Ping

    2013-01-01

    Lipases are one of the most important biocatalysts for biotechnological applications. Immobilization is an efficient method to increase the stability and reusability of lipases. In this study, nanoporous gold (NPG), a new kind of nanoporous material with tunable porosity and excellent biocompatibility, was employed as an effective support for lipase immobilization. The pore size of NPG and adsorption time played key roles in the construction of lipase-NPG biocomposites. The morphology and com...

  13. Brown Adipose Tissue Activation Is Linked to Distinct Systemic Effects on Lipid Metabolism in Humans.

    Chondronikola, Maria; Volpi, Elena; Børsheim, Elisabet; Porter, Craig; Saraf, Manish K; Annamalai, Palam; Yfanti, Christina; Chao, Tony; Wong, Daniel; Shinoda, Kosaku; Labbė, Sebastien M; Hurren, Nicholas M; Cesani, Fernardo; Kajimura, Shingo; Sidossis, Labros S

    2016-06-14

    Recent studies suggest that brown adipose tissue (BAT) plays a role in energy and glucose metabolism in humans. However, the physiological significance of human BAT in lipid metabolism remains unknown. We studied 16 overweight/obese men during prolonged, non-shivering cold and thermoneutral conditions using stable isotopic tracer methodologies in conjunction with hyperinsulinemic-euglycemic clamps and BAT and white adipose tissue (WAT) biopsies. BAT volume was significantly associated with increased whole-body lipolysis, triglyceride-free fatty acid (FFA) cycling, FFA oxidation, and adipose tissue insulin sensitivity. Functional analysis of BAT and WAT demonstrated the greater thermogenic capacity of BAT compared to WAT, while molecular analysis revealed a cold-induced upregulation of genes involved in lipid metabolism only in BAT. The accelerated mobilization and oxidation of lipids upon BAT activation supports a putative role for BAT in the regulation of lipid metabolism in humans. PMID:27238638

  14. Overexpression of Rad in muscle worsens diet-induced insulin resistance and glucose intolerance and lowers plasma triglyceride level

    Ilany, Jacob; Bilan, Philip J.; Kapur, Sonia; Caldwell, James S.; Patti, Mary-Elizabeth; Marette, Andre; Kahn, C. Ronald

    2006-03-01

    Rad is a low molecular weight GTPase that is overexpressed in skeletal muscle of some patients with type 2 diabetes mellitus and/or obesity. Overexpression of Rad in adipocytes and muscle cells in culture results in diminished insulin-stimulated glucose uptake. To further elucidate the potential role of Rad in vivo, we have generated transgenic (tg) mice that overexpress Rad in muscle using the muscle creatine kinase (MCK) promoter-enhancer. Rad tg mice have a 6- to 12-fold increase in Rad expression in muscle as compared to wild-type littermates. Rad tg mice grow normally and have normal glucose tolerance and insulin sensitivity, but have reduced plasma triglyceride levels. On a high-fat diet, Rad tg mice develop more severe glucose intolerance than the wild-type mice; this is due to increased insulin resistance in muscle, as exemplified by a rightward shift in the dose-response curve for insulin stimulated 2-deoxyglucose uptake. There is also a unexpected further reduction of the plasma triglyceride levels that is associated with increased levels of lipoprotein lipase in the Rad tg mice. These results demonstrate a potential synergistic interaction between increased expression of Rad and high-fat diet in creation of insulin resistance and altered lipid metabolism present in type 2 diabetes. diabetes mellitus | glucose transport | RGK GTPase | transgenic mouse

  15. Lipase production by diverse phylogenetic clades of Aureobasidium pullulans

    Thirty-nine strains representing 12 diverse phylogenetic clades of Aureobasidium pullulans were surveyed for lipase production using a quantitative assay. Strains in clades 4 and 10 produced 0.2-0.3 U lipase/ml, while color variant strain NRRL Y-2311-1 in clade 8 produced 0.54 U lipase/ml. Strains i...

  16. Physiological adaptations in adipose tissue of Brahman vs Angus heifers.

    Sprinkle, J E; Hansard, H S; Warrington, B G; Holloway, J W; Wu, G; Smith, S B

    1998-03-01

    Nonpregnant yearling Brahman (n = 12) and Angus (n = 12) heifers were equally allocated to two dietary treatments in a replicated study to examine responses in lipid metabolism to nutritional treatments consisting of a moderate energy diet (2.0 Mcal ME/kg) fed at maintenance and a 2.5 x maintenance high-energy diet (2.4 Mcal ME/kg) fed for 30 d. In vitro lipogenesis and the activities of lipoprotein lipase (LPL) and hormone-sensitive lipase (HSL) were determined in perianal subcutaneous adipose tissue biopsies at the start and end of the trial. At the start of the trial, breeds had similar (P > .10) rates of lipogenesis and LPL activity. Brahman had greater (P Angus at the start of the trial and tended (P .10) HSL activity. Heifers on the high-energy, higher-intake diet had greater lipogenesis (P .10) rates of lipogenesis at the end of the trial. When adjusted for BCS nested within breed, Brahman had greater (P Angus. PMID:9535333

  17. ATGL has a key role in lipid droplet/adiposome degradation in mammalian cells

    Smirnova, Elena; Goldberg, Elysa B; Makarova, Kira S; Lin, Lin; Brown, William J.; Jackson, Catherine L.

    2005-01-01

    Lipid droplets (LDs), also called adiposomes, are found in many eukaryotic cells, and are highly upregulated in lipid-storage cells, such as adipocytes. The mechanism by which adiposomes and their component neutral lipids are degraded is an important health issue with the rapidly spreading epidemic of obesity. Recently, a novel triglyceride lipase (adipose triglyceride lipase (ATGL)) that catalyses the initial step in triglyceride hydrolysis in adipocyte LDs was identified. Here, we show that...

  18. Lipase and protease extraction from activated sludge

    Gessesse, Amare; Dueholm, Thomas; Petersen, Steffen B.;

    2003-01-01

    gentle and efficient enzyme extraction methods from environmental samples is very important. In this study we present a method for the extraction of lipases and proteases from activated sludge using the non-ionic detergent Triton X-100, EDTA, and cation exchange resin (CER), alone or in combination for......In the process of wastewater treatment hydrolysis of polymeric substances is the first and rate-limiting step. A closer study of the enzymes catalysing these reactions is essential for a better understanding of the microbial activity in the wastewater treatment process. Therefore, development of...... the extraction of lipases and proteases from activated sludge. The sludge was continuously stirred in the presence of either buffer alone or in the presence of detergent and/or chelating agents. In all cases, a marked reduction in floc size was observed upon continuous stirring. However, no lipase...

  19. Bioengineering beige adipose tissue therapeutics

    Kevin eTharp

    2015-10-01

    Full Text Available Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of UCP1-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable brown adipose tissues for human therapeutic purposes at this time.Recent developments in bioengineering, including novel hyaluronic acid based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit WAT derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of beige adipose tissue implants and their potential for the metabolic

  20. Bioengineering Beige Adipose Tissue Therapeutics.

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiologically beneficial reductions in circulating glucose and lipids. The recent discovery that brown adipose tissue (BAT)-derived secreted factors positively alter whole body metabolism further expands potential benefits of brown or beige/brite adipose expansion. Unfortunately, there are no sources of transplantable BATs for human therapeutic purposes at this time. Recent developments in bioengineering, including novel hyaluronic acid-based hydrogels, have enabled non-immunogenic, functional tissue allografts that can be used to generate large quantities of UCP1-positive adipose tissue. These sophisticated tissue-engineering systems have provided the methodology to develop metabolically active brown or beige/brite adipose tissue implants with the potential to be used as a metabolic therapy. Unlike the pharmacological browning of white adipose depots, implantation of bioengineered UCP1-positive adipose tissues offers a spatially controlled therapeutic. Moving forward, new insights into the mechanisms by which extracellular cues govern stem-cell differentiation and progenitor cell recruitment may enable cell-free matrix implant approaches, which generate a niche sufficient to recruit white adipose tissue-derived stem cells and support their differentiation into functional beige/brite adipose tissues. This review summarizes clinically relevant discoveries in tissue-engineering and biology leading toward the recent development of biomaterial supported beige adipose tissue implants and

  1. Preventing diet-induced obesity in mice by adipose tissue transformation and angiogenesis using targeted nanoparticles.

    Xue, Yuan; Xu, Xiaoyang; Zhang, Xue-Qing; Farokhzad, Omid C; Langer, Robert

    2016-05-17

    The incidence of obesity, which is recognized by the American Medical Association as a disease, has nearly doubled since 1980, and obesity-related comorbidities have become a major threat to human health. Given that adipose tissue expansion and transformation require active growth of new blood vasculature, angiogenesis offers a potential target for the treatment of obesity-associated disorders. Here we construct two peptide-functionalized nanoparticle (NP) platforms to deliver either Peroxisome Proliferator-Activated Receptor gamma (PPARgamma) activator rosiglitazone (Rosi) or prostaglandin E2 analog (16,16-dimethyl PGE2) to adipose tissue vasculature. These NPs were engineered through self-assembly of a biodegradable triblock polymer composed of end-to-end linkages between poly(lactic-coglycolic acid)-b-poly(ethylene glycol) (PLGA-b-PEG) and an endothelial-targeted peptide. In this system, released Rosi promotes both transformation of white adipose tissue (WAT) into brown-like adipose tissue and angiogenesis, which facilitates the homing of targeted NPs to adipose angiogenic vessels, thereby amplifying their delivery. We show that i.v. administration of these NPs can target WAT vasculature, stimulate the angiogenesis that is required for the transformation of adipose tissue, and transform WAT into brown-like adipose tissue, by the up-regulation of angiogenesis and brown adipose tissue markers. In a diet-induced obese mouse model, these angiogenesis-targeted NPs have inhibited body weight gain and modulated several serological markers including cholesterol, triglyceride, and insulin, compared with the control group. These findings suggest that angiogenesis-targeting moieties with angiogenic stimulator-loaded NPs could be incorporated into effective therapeutic regimens for clinical treatment of obesity and other metabolic diseases. PMID:27140638

  2. Lipase biocatalysis for useful biodegradable products

    Linko, Y.Y.; Wang, Zhuo Lin; Uosukainen, E.; Seppaelae, J. [Helsinki Univ. of Technology, Espoo (Finland); Laemsae, M. [Raisio Group Oil Milling Industry, Raisio (Finland)

    1996-12-31

    It was shown that lipases can be used as biocatalysts in the production of useful biodegradable compounds such as 1-butyl oleate by direct esterification of butanol and oleic acid to decrease viscosity of biodiesel in winter use. By enzymic transesterification, a mixture of 2-ethyl-1-hexyl esters from rapeseed oil fatty acids can be obtained in good yields for use as a solvent, and of trimethylolpropane esters for use as a lubricant. Finally, it was demonstrated that polyesters with a mass average molar mass in excess of 75,000 g mol{sup -}1 can be obtained by esterification or transesterification by using lipase as biocatalyst. (author) (3 refs.)

  3. Hepatic Lipase: a Comprehensive View of its Role on Plasma Lipid and Lipoprotein Metabolism.

    Kobayashi, Junji; Miyashita, Kazuya; Nakajima, Katsuyuki; Mabuchi, Hiroshi

    2015-01-01

    Hepatic lipase (HL) is a key enzyme catalyzing the hydrolysis of triglycerides (TG) and phospholipids (PLs) in several lipoproteins. It is generally recognized that HL is involved in the remodeling of remnant, low-density lipoprotein (LDL), high-density lipoprotein (HDL) and the production of small, dense low-density lipoproteins (sd-LDLs).On the other hand, it is unclear whether HL accelerates or retards atherosclerosis. From the clinical point of view, HL deficiency may provide useful information on answering this question, but the rarity of this disease makes it impossible to conduct epidemiological study.In this review, we describe a comprehensive and updated view of the clinical significance of HL on lipid and lipoprotein metabolism. PMID:26194979

  4. Hormone-sensitive lipase deficiency suppresses insulin secretion from pancreatic islets of Lepob/ob mice

    It has long been a matter of debate whether the hormone-sensitive lipase (HSL)-mediated lipolysis in pancreatic β-cells can affect insulin secretion through the alteration of lipotoxicity. We generated mice lacking both leptin and HSL (Lepob/ob/HSL-/-) and explored the role of HSL in pancreatic β-cells in the setting of obesity. Lepob/ob/HSL-/- developed elevated blood glucose levels and reduced plasma insulin levels compared with Lepob/ob/HSL+/+ in a fed state, while the deficiency of HSL did not affect glucose homeostasis in Lep+/+ background. The deficiency of HSL exacerbated the accumulation of triglycerides in Lepob/ob islets, leading to reduced glucose-stimulated insulin secretion. The deficiency of HSL also diminished the islet mass in Lepob/ob mice due to decreased cell proliferation. In conclusion, HSL affects insulin secretary capacity especially in the setting of obesity.

  5. Triglyceride Glucose-Body Mass Index Is a Simple and Clinically Useful Surrogate Marker for Insulin Resistance in Nondiabetic Individuals.

    Leay-Kiaw Er

    Full Text Available Insulin resistance (IR and the consequences of compensatory hyperinsulinemia are pathogenic factors for a set of metabolic abnormalities, which contribute to the development of diabetes mellitus and cardiovascular diseases. We compared traditional lipid levels and ratios and combined them with fasting plasma glucose (FPG levels or adiposity status for determining their efficiency as independent risk factors for IR.We enrolled 511 Taiwanese individuals for the analysis. The clinical usefulness of various parameters--such as traditional lipid levels and ratios; visceral adiposity indicators, visceral adiposity index (VAI, and lipid accumulation product (LAP; the product of triglyceride (TG and FPG (the TyG index; TyG with adiposity status (TyG-body mass index [BMI] and TyG-waist circumference index [WC]; and adipokine levels and ratios--was analyzed to identify IR.For all lipid ratios, the TG/high-density lipoprotein cholesterol (HDL-C ratio had the highest additional percentage of variation in the homeostasis model assessment of insulin resistance (HOMA-IR; 7.0% in total; for all variables of interest, TyG-BMI and leptin-adiponectin ratio (LAR were strongly associated with HOMA-IR, with 16.6% and 23.2% of variability, respectively. A logistic regression analysis revealed similar patterns. A receiver operating characteristic (ROC curve analysis indicated that TG/HDL-C was a more efficient IR discriminator than other lipid variables or ratios. The area under the ROC curve (AUC for VAI (0.734 and TyG (0.708 was larger than that for TG/HDL-C (0.707. TyG-BMI and LAR had the largest AUC (0.801 and 0.801, respectively.TyG-BMI is a simple, powerful, and clinically useful surrogate marker for early identification of IR.

  6. Methodologies to assess paediatric adiposity.

    Horan, M

    2014-05-04

    Childhood obesity is associated with increased risk of adult obesity, cardiovascular disease, diabetes and cancer. Appropriate techniques for assessment of childhood adiposity are required to identify children at risk. The aim of this review was to examine core clinical measurements and more technical tools to assess paediatric adiposity.

  7. Salsalate activates brown adipose tissue in mice.

    van Dam, Andrea D; Nahon, Kimberly J; Kooijman, Sander; van den Berg, Susan M; Kanhai, Anish A; Kikuchi, Takuya; Heemskerk, Mattijs M; van Harmelen, Vanessa; Lombès, Marc; van den Hoek, Anita M; de Winther, Menno P J; Lutgens, Esther; Guigas, Bruno; Rensen, Patrick C N; Boon, Mariëtte R

    2015-05-01

    Salsalate improves glucose intolerance and dyslipidemia in type 2 diabetes patients, but the mechanism is still unknown. The aim of the current study was to unravel the molecular mechanisms involved in these beneficial metabolic effects of salsalate by treating mice with salsalate during and after development of high-fat diet-induced obesity. We found that salsalate attenuated and reversed high-fat diet-induced weight gain, in particular fat mass accumulation, improved glucose tolerance, and lowered plasma triglyceride levels. Mechanistically, salsalate selectively promoted the uptake of fatty acids from glycerol tri[(3)H]oleate-labeled lipoprotein-like emulsion particles by brown adipose tissue (BAT), decreased the intracellular lipid content in BAT, and increased rectal temperature, all pointing to more active BAT. The treatment of differentiated T37i brown adipocytes with salsalate increased uncoupled respiration. Moreover, salsalate upregulated Ucp1 expression and enhanced glycerol release, a dual effect that was abolished by the inhibition of cAMP-dependent protein kinase (PKA). In conclusion, salsalate activates BAT, presumably by directly activating brown adipocytes via the PKA pathway, suggesting a novel mechanism that may explain its beneficial metabolic effects in type 2 diabetes patients. PMID:25475439

  8. Subcutaneous Adipose Tissue Transplantation in Diet-Induced Obese Mice Attenuates Metabolic Dysregulation While Removal Exacerbates It.

    Foster, M T; Softic, S; Caldwell, J; Kohli, R; de Kloet, A D; Seeley, R J

    2013-08-01

    Adipose tissue distribution is an important determinant of obesity-related comorbidities. It is well established that central obesity (visceral adipose tissue accumulation) is a risk factor for many adverse health consequences such as dyslipidemia, insulin resistance and type-2-diabetes. We hypothesize that the metabolic dysregulation that occurs following high fat diet-induced increases in adiposity are due to alterations in visceral adipose tissue function which influence lipid flux to the liver via the portal vein. This metabolic pathology is not exclusively due to increases in visceral adipose tissue mass but also driven by intrinsic characteristics of this particular depot. In Experiment 1, high fat diet (HFD)-induced obese control (abdominal incision, but no fat manipulation) or autologous (excision and subsequent relocation of adipose tissue) subcutaneous tissue transplantation to the visceral cavity. In Experiment 2 mice received control surgery, subcutaneous fat removal or hetero-transplantation (tissue from obese donor) to the visceral cavity. Body composition analysis and glucose tolerance tests were performed 4 weeks post-surgery. Adipose mass and portal adipokines, cytokines, lipids and insulin were measured from samples collected at 5 weeks post-surgery. Auto- and hetero- transplantation in obese mice improved glucose tolerance, decreased systemic insulin concentration and reduced portal lipids and hepatic triglycerides compared with HFD controls. Hetero-transplantation of subcutaneous adipose tissue to the visceral cavity in obese mice restored hepatic insulin sensitivity and reduced insulin and leptin concentrations to chow control levels. Fat removal, however, as an independent procedure exacerbated obesity-induced increases in leptin and insulin concentrations. Overall subcutaneous adipose tissue protects against aspects of metabolic dysregulation in obese mice. Transplantation-induced improvements do not occur via enhanced storage of lipid in

  9. Activities of asymmetric dimethylarginine-related enzymes in white adipose tissue are associated with circulating lipid biomarkers

    Iwasaki Hiroaki

    2012-04-01

    Full Text Available Abstract Background Asymmetric NG,NG-dimethylarginine (ADMA, an endogenous inhibitor of nitric oxide synthase, is regulated by the enzymatic participants of synthetic and metabolic processes, i.e., type I protein N-arginine methyltransferase (PRMT and dimethylarginine dimethylaminohydrolase (DDAH. Previous reports have demonstrated that circulating ADMA levels can vary in patients with type 1 and type 2 diabetes mellitus (T2DM. White adipose tissue expresses the full enzymatic machinery necessary for ADMA production and metabolism; however, modulation of the activities of adipose ADMA-related enzymes in T2DM remains to be determined. Methods A rodent model of T2DM using 11- and 20-week old Goto-Kakizaki (GK rats was used. The expression and catalytic activity of PRMT1 and DDAH1 and 2 in the white adipose tissues (periepididymal, visceral and subcutaneous fats and femur skeletal muscle tissue were determined by immunoblotting, in vitro methyltransferase and in vitro citrulline assays. Results Non-obese diabetic GK rats showed low expression and activity of adipose PRMT1 compared to age-matched Wistar controls. Adipose tissues from the periepididymal, visceral and subcutaneous fats of GK rats had high DDAH1 expression and total DDAH activity, whereas the DDAH2 expression was lowered below the control value. This dynamic of ADMA-related enzymes in white adipose tissues was distinct from that of skeletal muscle tissue. GK rats had lower levels of serum non-esterified fatty acids (NEFA and triglycerides (TG than the control rats. In all subjects the adipose PRMT1 and DDAH activities were statistically correlated with the levels of serum NEFA and TG. Conclusion Activities of PRMT1 and DDAH in white adipose tissues were altered in diabetic GK rats in an organ-specific manner, which was reflected in the serum levels of NEFA and TG. Changes in adipose ADMA-related enzymes might play a part in the function of white adipose tissue.

  10. Anti-obesity activity of hen egg anti-lipase immunoglobulin yolk, a novel pancreatic lipase inhibitor

    Hirose, Mai; Ando, Taishi; Shofiqur, Rahman; Umeda, Kouji; Kodama, Yoshikatsu; Van Nguyen, Sa; Goto, Tsuyoshi; Shimada, Masaya; Nagaoka, Satoshi

    2013-01-01

    Background There is completely no report about both hen egg anti-lipase immunoglobulin yolk (IgY) and its anti-obesity action. Thus, we tried to isolate and characterize a novel anti-lipase immunoglobulin from hen egg yolk. Moreover, we investigated whether hen egg yolk anti-lipase IgY inhibits pancreatic lipase activity in vitro, and examined its ability to prevent obesity in a murine high fat diet-induced obesity model. Methods We determined the inhibitory action of Anti-lipase IgY on lipas...

  11. Lagenaria siceraria ameliorates atheromatous lesions by modulating HMG-CoA reductase and lipoprotein lipase enzymes activity in hypercholesterolemic rats

    Mithun Singh Rajput; Neelam Balekar; Dinesh Kumar Jain

    2014-01-01

    Objective:To investigate the antiatherosclerotic potential ofLagenaria siceraria(L. siceraria) by calculating percentage plaque area in aorta and grade of atheromatous lesions modulated byHMG-CoA reductase enzyme and lipoprotein lipase enzymes levels in hyperlipidemic rats. Methods:Rats were divided into different groups, fed with high cholesterol atherogenic diet and in addition supplemented with ethanolic extract of fruits ofL. siceraria and standard drug atorvastatin.At the end of the treatment schedule, the atherosclerotic lesion area was measured in cross-sections of the aortic root and grading of atherosclerotic lesions was done.The blood samples from animals of different groups were evaluated for serum lipid profile determination and plasma lipoprotein lipase activity and the hepaticHMG-CoA activity was also determined. Results:Treatment of rats with ethanolic extract of fruits ofL. siceraria significantly lowers the risk of atherosclerosis by lowering percentage plaque area in aorta and grade of atheromatous lesions in hypercholesterolemic rats and also serum cholesterol, triglyceride,LDL-c,VLDL-c and increasedHDL-c levels as well.The extract also induced lipoprotein lipase activity and significantly decreased cholesterogenesis inliver by reducingHMG-CoA reductase activity in hypercholeaterolemic rats.Conclusion:It can be concluded that ethanolic extract of fruits of L. siceraria contains active components which ameliorates the atheromatous lesions in rat aorta and lowers the risk of atherosclerosis in hypercholesterolemic rats.

  12. [Lack of association between the S447X variant of the lipoprotein lipase gene and plasma lipids. A preliminary study].

    Zambrano Morales, Mariana; Fernández Salgado, Erika; Balzán Urdaneta, Ligia; Labastidas, Neila; Aranguren-Méndez, José; Connell, Lissette; Molero Paredes, Tania; Rojas, Alicia; Panunzio, Amelia

    2014-06-01

    The increase in lipid plasma values is an important cardiovascular risk factor. Lipoprotein lipase (LPL) plays an important role in the lipoprotein metabolism and metabolic and genetic factors may influence its levels and functions. The S447X variant of the lipoprotein lipase gene is associated with changes in plasma lipids in different populations. The objective of this research was to analyze the S447X variant of the LPL gene and its relation with plasma lipids of individuals in Zulia state, Venezuela. With this purpose, we studied 75 individuals (34 men and 41 women) between 20 and 60 years of age. Each subject had a medical history which included family history, anthropometric characteristics, nutritional status evaluation and biochemical tests. Genomic DNA was extracted for the molecular study and the polymerase chain reaction was used, followed by enzyme digestion, for restriction fragments length polymorphisms using the Hinf I enzyme. The individuals studied had normal levels of blood glucose, triglycerides, total cholesterol and low density lipoproteins (LDL-C) and slightly decreased levels of high density lipoproteins (HDL-C). The genotypic distribution of the LPL gene S447X variant in the studied population was 90.6% for the homozygous genotype SS447 and 9.4% for the heterozygote SX447. The genotype 447XX was not identified. The population was found in Hardy Weinberg genetic equilibrium. No association between the S447X polymorphism of lipoprotein lipase gene and plasma lipids was observed. PMID:24974629

  13. [The characterization of microbial lipases. 1. The determination of lipase activity].

    Bariszlovich, M; Meusel, D; Tülsner, M

    1990-01-01

    In the selection of an appropriate method for activity determination of lipases existing technical equipment, kind of enzymes, number of samples investigated (e.g. in routine analysis), and expected sensitivity range have to be taken into account. Titrimetric methods and above all copper salt methods with their high detection sensitivity are the most suitable procedures for activity determination of lipases used in laboratories and institutions without equipment for radiochemical analysis. PMID:2233988

  14. Immobilization of a Commercial Lipase from Penicillium camembertii (Lipase G) by Different Strategies

    Adriano A. Mendes; Larissa Freitas; de Carvalho, Ana Karine F.; de Oliveira, Pedro C.; Heizir F. de Castro

    2011-01-01

    The objective of this work was to select the most suitable procedure to immobilize lipase from Penicillium camembertii (Lipase G). Different techniques and supports were evaluated, including physical adsorption on hydrophobic supports octyl-agarose, poly(hydroxybutyrate) and Amberlite resin XAD-4; ionic adsorption on the anionic exchange resin MANAE-agarose and covalent attachment on glyoxyl-agarose, MANAE-agarose cross-linked with glutaraldehyde, MANAE-agarose-glutaraldehyde, and epoxy-silic...

  15. New eutectic ionic liquids for lipase activation and enzymatic preparation of biodiesel†

    Zhao, Hua; Baker, Gary A.; Holmes, Shaletha

    2012-01-01

    The enzymatic preparation of biodiesel has been hampered by the lack of suitable solvents with desirable properties such as high lipase compatibility, low cost, low viscosity, high biodegradability, and ease of product separation. Recent interest in using ionic liquids (ILs) as advanced reaction media has led to fast reaction rates and high yields in the enzymatic synthesis of biodiesel. However, conventional (i.e., cation–anion paired) ILs based on imidazolium and other quaternary ammonium salts remain too expensive for wide application at industrial scales. In this study, we report on newly-synthesized eutectic ILs derived from choline acetate or choline chloride coupled with biocompatible hydrogen-bond donors, such as glycerol. These eutectic solvents have favorable properties including low viscosity, high biodegradability, and excellent compatibility with Novozym® 435, a commercial immobilized Candida antarctica lipase B. Furthermore, in a model biodiesel synthesis system, we demonstrate high reaction rates for the enzymatic transesterification of Miglyol® oil 812 with methanol, catalyzed by Novozym® 435 in choline acetate/glycerol (1 : 1.5 molar ratio). The high conversion (97%) of the triglyceride obtained within 3 h, under optimal conditions, suggests that these novel eutectic solvents warrant further exploration as potential media in the enzymatic production of biodiesel. PMID:21283901

  16. Ionic liquids increase the catalytic efficiency of a lipase (Lip1) from an antarctic thermophilic bacterium.

    Muñoz, Patricio A; Correa-Llantén, Daniela N; Blamey, Jenny M

    2015-01-01

    Lipases catalyze the hydrolysis and synthesis of triglycerides and their reactions are widely used in industry. The use of ionic liquids has been explored in order to improve their catalytic properties. However, the effect of these compounds on kinetic parameters of lipases has been poorly understood. A study of the kinetic parameters of Lip1, the most thermostable lipase from the supernatant of the strain ID17, a thermophilic bacterium isolated from Deception Island, Antarctica, and a member of the genus Geobacillus is presented. Kinetic parameters of Lip1 were modulated by the use of ionic liquids BmimPF6 and BmimBF4. The maximum reaction rate of Lip1 was improved in the presence of both salts. The highest effect was observed when BmimPF6 was added in the reaction mix, resulting in a higher hydrolytic activity and in a modulation of the catalytic efficiency of the enzyme. However, the catalytic efficiency did not change in the presence of BmimBF4. The increase of the reaction rates of Lip1 promoted by these ionic liquids could be related to possible changes in the Lip1 structure. This effect was measured by quenching of tryptophan fluorescence of the enzyme, when it was incubated with each liquid salt. In conclusion, the hydrolytic activity of Lip1 is modulated by the ionic liquids BmimBF4 and BmimPF6, improving the reaction rate and the catalytic efficiency of this enzyme when BmimPF6 was used. This effect is probably due to changes in the structure of Lip1 induced by the presence of these ionic liquids, stimulating its catalytic activity. PMID:25425150

  17. Structure of Human Pancreatic Lipase-Related Protein 2 with the Lid in an Open Conformation

    Eydoux, Cecilia; Spinelli, Silvia; Davis, Tara L.; Walker, John R.; Seitova, Alma; Dhe-Paganon, Sirano; De Caro, Alain; Cambillau, Christian; Carriere, Frederic (CNRS-UMR); (Toronto)

    2008-10-02

    Access to the active site of pancreatic lipase (PL) is controlled by a surface loop, the lid, which normally undergoes conformational changes only upon addition of lipids or amphiphiles. Structures of PL with their lids in the open and functional conformation have required cocrystallization with amphiphiles. Here we report two crystal structures of wild-type and unglycosylated human pancreatic lipase-related protein 2 (HPLRP2) with the lid in an open conformation in the absence of amphiphiles. These structures solved independently are strikingly similar, with some residues of the lid being poorly defined in the electron-density map. The open conformation of the lid is however different from that previously observed in classical liganded PL, suggesting different kinetic properties for HPLRP2. Here we show that the HPLRP2 is directly inhibited by E600, does not present interfacial activation, and acts preferentially on substrates forming monomers or small aggregates (micelles) dispersed in solution like monoglycerides, phospholipids and galactolipids, whereas classical PL displays reverse properties and a high specificity for unsoluble substrates like triglycerides and diglycerides forming oil-in-water interfaces. These biochemical properties imply that the lid of HPLRP2 is likely to spontaneously adopt in solution the open conformation observed in the crystal structure. This open conformation generates a large cavity capable of accommodating the digalactose polar head of galactolipids, similar to that previously observed in the active site of the guinea pig PLRP2, but absent from the classical PL. Most of the structural and kinetic properties of HPLRP2 were found to be different from those of rat PLRP2, the structure of which was previously obtained with the lid in a closed conformation. Our findings illustrate the essential role of the lid in determining the substrate specificity and the mechanism of action of lipases.

  18. Sleep deprivation affects inflammatory marker expression in adipose tissue

    Santos Ronaldo VT

    2010-10-01

    Full Text Available Abstract Sleep deprivation has been shown to increase inflammatory markers in rat sera and peripheral blood mononuclear cells. Inflammation is a condition associated with pathologies such as obesity, cancer, and cardiovascular diseases. We investigated changes in the pro and anti-inflammatory cytokines and adipokines in different depots of white adipose tissue in rats. We also assessed lipid profiles and serum levels of corticosterone, leptin, and adiponectin after 96 hours of sleep deprivation. Methods The study consisted of two groups: a control (C group and a paradoxical sleep deprivation by 96 h (PSD group. Ten rats were randomly assigned to either the control group (C or the PSD. Mesenteric (MEAT and retroperitoneal (RPAT adipose tissue, liver and serum were collected following completion of the PSD protocol. Levels of interleukin (IL-6, interleukin (IL-10 and tumour necrosis factor (TNF-α were analysed in MEAT and RPAT, and leptin, adiponectin, glucose, corticosterone and lipid profile levels were analysed in serum. Results IL-6 levels were elevated in RPAT but remained unchanged in MEAT after PSD. IL-10 protein concentration was not altered in either depot, and TNF-α levels decreased in MEAT. Glucose, triglycerides (TG, VLDL and leptin decreased in serum after 96 hours of PSD; adiponectin was not altered and corticosterone was increased. Conclusion PSD decreased fat mass and may modulate the cytokine content in different depots of adipose tissue. The inflammatory response was diminished in both depots of adipose tissue, with increased IL-6 levels in RPAT and decreased TNF-α protein concentrations in MEAT and increased levels of corticosterone in serum.

  19. Evaluation of the immediate vascular stability of lipoprotein lipase-generated 2-monoacylglycerol in mice

    Kleberg, Karen; Nielsen, Louise Lundeman; Stuhr-Hansen, Nicolai; Nielsen, John; Hansen, Harald Severin

    2014-01-01

    2-Monoacylglycerols are gaining increasing interest as signaling lipids, beyond endocannabinoids, for example, as ligands for the receptor GPR119 and as mediators of insulin secretion. In the vascular system, they are formed by the action of lipoprotein lipase (LPL); however, their further...... after intravenous coadministration in a ratio of 1:1 to mice. We found that peripheral tissues and the liver in particular are able to take up 2-monoacylglycerols as seen from 3H uptake. In muscle and adipose tissue, 2-monoacylglycerols are probably further hydrolyzed as seen by an increased 3H/14C...... ratio, whereas in the liver and the heart, data suggest that they are also subjected to re-esterification to triacylglycerol, as seen by an unchanged 3H/14C ratio in the lipid fraction of the tissues. Our findings suggest that LPL-generated 2-monoacylglycerol is likely to be stable in the vascular...

  20. KARAKTERISASI SIFAT-SIFAT BIOKIMIA EKSTRAK KASAR LIPASE EKSTRASELULER BAKTERI Azospirillum sp.PRD1

    Santi Nur Handayani; Puji Lestari; Oedjijono; Tri Joko Raharjo; Sabirin Matsjeh

    2011-01-01

    Enzim lipase mempunyai peranan penting dalam katalis berbagai reaksi industri satu diantaranya pembuatan flavor melalui reaksi esterifikasi. Lipase adalah biokatalis yang berperan besar dalam aplikasi bioteknologi, seperti dalam sintesis biopolimer, biodiesel, produksi obat, dan produksi flavor. Peningkatan penggunaan lipase untuk industri mendorong dilakukan penelitian untuk mendapatkan sumber-sumber lipase baru. Sumber lipase yang potensial salah satunya adalah bakteri Azospirillum sp.PRD1 ...

  1. [Residual risk: The roles of triglycerides and high density lipoproteins].

    Grammer, Tanja; Kleber, Marcus; Silbernagel, Günther; Scharnagl, Hubert; März, Winfried

    2016-06-01

    In clinical trials, the reduction of LDL-cholesterol (LDL-C) with statins reduces the incidence rate of cardiovascular events by approximately one third. This means, that a sizeable "residual risk" remains. Besides high lipoprotein (a), disorders in the metabolism of triglyceride-rich lipoproteins and high density liproteins have been implicated as effectors of the residual risk. Both lipoprotein parameters correlate inversely with each other. Therefore, the etiological contributions of triglycerides and / or of HDL for developing cardiovascular disease can hardly be estimated from either observational studies or from intervention studies. The largely disappointing results of intervention studies with inhibitors of the cholesteryl ester transfer protein and in particular the available set of genetically-epidemiological studies suggest that in the last decade, the importance of HDL cholesterol has been overvalued, while the importance of triglycerides has been underestimated. High triglycerides not always atherogenic, but only if they are associated with the accumulation relatively cholesterol-enriched, incompletely catabolized remnants of chylomicrons and very low density lipoproteins (familial type III hyperlipidemia, metabolic syndrome, diabetes mellitus). The normalization of the concentration of triglycerides and remnants by inhibiting the expression of apolipoprotein C3 is hence a new, promising therapeutic target. PMID:27305303

  2. Polyphenolic Compounds as Pancreatic Lipase Inhibitors.

    Buchholz, Tina; Melzig, Matthias F

    2015-07-01

    Obesity and its associated diseases such as diabetes mellitus and coronary heart diseases are a major challenge for our society. An important target for the treatment of obesity includes the development of inhibitors of nutrient digestion and absorption. Inhibition of pancreatic lipase and the associated reduction of lipid absorption is an attractive approach for the discovery of potent agents. Currently, the only clinically approved pharmacologic agent as pancreatic lipase inhibitor is Orlistat. However, its usage is compromised by unpleasant gastrointestinal adverse reactions (oily stools, oily spotting, flatulence). The use of botanical materials as a potential source of new drugs is of increasing importance and application. Natural products that are interesting for obesity treatment are generally considered to have less toxic and side effects than totally synthetic drugs. One of the most important sources of potential pancreatic lipase inhibitors represents the class of polyphenols. This article summarizes most studied subclasses of polyphenols including flavonoids, hydroxycinnamic acids, hydroxybenzoic acids and lignans with pancreatic lipase inhibitory effects. A structural comparison of potent inhibitors shows an increased inhibitory effect depending on number and position of phenolic hydroxyl groups, degree of polymerization and elimination of glycosylation during digestion. PMID:26132857

  3. New Extremophilic Lipases and Esterases from Metagenomics

    López-López, Olalla; Cerdán, Maria E; González Siso, Maria I

    2014-01-01

    Lipolytic enzymes catalyze the hydrolysis of ester bonds in the presence of water. In media with low water content or in organic solvents, they can catalyze synthetic reactions such as esterification and transesterification. Lipases and esterases, in particular those from extremophilic origin, are robust enzymes, functional under the harsh conditions of industrial processes owing to their inherent thermostability and resistance towards organic solvents, which combined with their high chemo-, regio- and enantioselectivity make them very attractive biocatalysts for a variety of industrial applications. Likewise, enzymes from extremophile sources can provide additional features such as activity at extreme temperatures, extreme pH values or high salinity levels, which could be interesting for certain purposes. New lipases and esterases have traditionally been discovered by the isolation of microbial strains producing lipolytic activity. The Genome Projects Era allowed genome mining, exploiting homology with known lipases and esterases, to be used in the search for new enzymes. The Metagenomic Era meant a step forward in this field with the study of the metagenome, the pool of genomes in an environmental microbial community. Current molecular biology techniques make it possible to construct total environmental DNA libraries, including the genomes of unculturable organisms, opening a new window to a vast field of unknown enzymes with new and unique properties. Here, we review the latest advances and findings from research into new extremophilic lipases and esterases, using metagenomic approaches, and their potential industrial and biotechnological applications. PMID:24588890

  4. Microbial lipases: Production, properties and biotechnological applications

    Josana Maria Messias

    2011-09-01

    Full Text Available Lipases belong to the group of hydrolases that catalyze the hydrolysis of triacylglycerol lipids to free fatty acids and glycerol. They have significant potential biotechnological applications in catalyzing organic synthesis reactions in non-aqueous solvents using simplified procedures resulting in conversions of high yields. Lipase production has conventionally been performed by submerged fermentation; however, solid-state fermentation processes have been prominent when residues are used as substrates because they serve as low-cost nutrient sources. Microbial lipases can be used as additives in foods to modify and enhance organoleptic properties, as well as in detergents to hydrolyse fats in the treatment of oily effluents, and also have value for pharmaceutical, cosmetic, agrochemical, and oil chemical industries. More recently, they are used in transesterification reactions to convert plant seed oils into biodiesel. The objective of this work was to review the published literature on the production, properties and applications of microbial lipases, and its biotechnological role in producing biodiesel.

  5. Structural characterization of MAPLE deposited lipase biofilm

    Aronne, Antonio; Ausanio, Giovanni; Bloisi, Francesco; Calabria, Raffaela; Califano, Valeria; Fanelli, Esther; Massoli, Patrizio; Vicari, Luciano R. M.

    2014-11-01

    Lipases (triacylglycerol ester hydrolases) are enzymes used in several industrial applications. Enzymes immobilization can be used to address key issues limiting widespread application at industrial level. Immobilization efficiency is related to the ability to preserve the native conformation of the enzyme. MAPLE (Matrix Assisted Pulsed Laser Evaporation) technique, a laser deposition procedure for treating organic/polymeric/biomaterials, was applied for the deposition of lipase enzyme in an ice matrix, using near infrared laser radiation. Microscopy analysis showed that the deposition occurred in micrometric and submicrometric clusters with a wide size distribution. AFM imaging showed that inter-cluster regions are uniformly covered with smaller aggregates of nanometric size. Fourier transform infrared spectroscopy was used for both recognizing the deposited material and analyzing its secondary structure. Results showed that the protein underwent reversible self-association during the deposition process. Actually, preliminary tests of MAPLE deposited lipase used for soybean oil transesterification with isopropyl alcohol followed by gas chromatography-mass spectrometry gave results consistent with undamaged deposition of lipase.

  6. Gastric Lipase Secretion in Children with Gastritis

    Krystyna Sztefko

    2013-07-01

    Full Text Available Gastric lipase is one of the prepancreatic lipases found in some mammalian species and in humans. Our knowledge of the hormonal regulation of gastric lipase secretion in children and adolescents is still very limited. The aim of this study was to compare the activity of human gastric lipase (HGL in gastric juice in healthy adolescents and in patients with gastritis. The adolescents were allocated to three groups: the first including patients with Helicobacter pylori gastritis (HPG; n = 10, the second including patients with superficial gastritis caused by pathogens other than H. pylori (non-HPG; n = 14 and the control group including healthy adolescents (n = 14. Activity of HGL was measured in gastric juice collected during endoscopy. Plasma concentrations of cholecystokinin (CCK, glucagon-like peptide-1 (GLP-1 and glucose-dependent insulinotropic peptide (GIP were measured in all adolescents. Activity of HGL in the non-HPG group was significantly lower than in the HPG group (p < 0.005 and the control group (p < 0.005. Mean plasma GIP levels in the control group were lower than in the non-HPG group (p < 0.003 and the HPG group (p < 0.01. We conclude that the regulation of HGL secretion by GLP-1 and CCK is altered in patients with gastritis. Moreover, GIP is a potent controller of HGL activity, both in healthy subjects and in patients with gastritis.

  7. LXR activation by GW3965 alters fat tissue distribution and adipose tissue inflammation in ob/ob female mice[S

    Archer, Amena; Stolarczyk, Émilie; Doria, Maria Luisa; Helguero, Luisa; Domingues, Rosário; Howard, Jane K; Mode, Agneta; Korach-André, Marion; Gustafsson, Jan-Åke

    2013-01-01

    To investigate the role of liver X receptor (LXR) in adipose tissue metabolism during obesity, ob/ob mice were treated for 5 weeks with the synthetic LXR agonist GW3965. MRI analysis revealed that pharmacological activation of LXR modified fat distribution by decreasing visceral (VS) fat and inversely increasing subcutaneous (SC) fat storage without affecting whole body fat content. This was concordant with opposite regulation by GW3965 of the lipolytic markers hormone-sensitive lipase (HSL) ...

  8. Genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the rat.

    Miloslava Hodúlová

    Full Text Available The plasma profile of major lipoprotein classes and its subdivision into particular fractions plays a crucial role in the pathogenesis of atherosclerosis and is a major predictor of coronary artery disease. Our aim was to identify genomic determinants of triglyceride and cholesterol distribution into lipoprotein fractions and lipoprotein particle sizes in the recombinant inbred rat set PXO, in which alleles of two rat models of the metabolic syndrome (SHR and PD inbred strains segregate together with those from Brown Norway rat strain. Adult male rats of 15 PXO strains (n = 8-13/strain and two progenitor strains SHR-Lx (n = 13 and BXH2/Cub (n = 18 were subjected to one-week of high-sucrose diet feeding. We performed association analyses of triglyceride (TG and cholesterol (C concentrations in 20 lipoprotein fractions and the size of major classes of lipoprotein particles utilizing 704 polymorphic microsatellite markers, the genome-wide significance was validated by 2,000 permutations per trait. Subsequent in silico focusing of the identified quantitative trait loci was completed using a map of over 20,000 single nucleotide polymorphisms. In most of the phenotypes we identified substantial gradient among the strains (e.g. VLDL-TG from 5.6 to 66.7 mg/dl. We have identified 14 loci (encompassing 1 to 65 genes on rat chromosomes 3, 4, 7, 8, 11 and 12 showing suggestive or significant association to one or more of the studied traits. PXO strains carrying the SHR allele displayed significantly higher values of the linked traits except for LDL-TG and adiposity index. Cholesterol concentrations in large, medium and very small LDL particles were significantly associated to a haplotype block spanning part of a single gene, low density lipoprotein receptor-related protein 1B (Lrp1b. Using genome-wide association we have identified new genetic determinants of triglyceride and cholesterol distribution into lipoprotein fractions in the recombinant

  9. Activation of Hormone-sensitive Lipase Requires Two Steps, Protein Phosphorylation and Binding to the PAT-1 Domain of Lipid Droplet Coat Proteins*

    Wang, Hong; Hu, Liping; Dalen, Knut; Dorward, Heidi; Marcinkiewicz, Amy; Russell, Deanna; Gong, Dawei; Londos, Constantine; Yamaguchi, Tomohiro; Holm, Cecilia; Rizzo, Mark A.; Brasaemle, Dawn; Sztalryd, Carole

    2009-01-01

    Lipolysis is an important metabolic pathway controlling energy homeostasis through degradation of triglycerides stored in lipid droplets and release of fatty acids. Lipid droplets of mammalian cells are coated with one or more members of the PAT protein family, which serve important functions in regulating lipolysis. In this study, we investigate the mechanisms by which PAT family members, perilipin A, adipose differentiation-related protein (ADFP), and LSDP5, control lipolysis catalyzed by h...

  10. Adipose tissue extract promotes adipose tissue regeneration in an adipose tissue engineering chamber model.

    Lu, Zijing; Yuan, Yi; Gao, Jianhua; Lu, Feng

    2016-05-01

    An adipose tissue engineering chamber model of spontaneous adipose tissue generation from an existing fat flap has been described. However, the chamber does not completely fill with adipose tissue in this model. Here, the effect of adipose tissue extract (ATE) on adipose tissue regeneration was investigated. In vitro, the adipogenic and angiogenic capacities of ATE were evaluated using Oil Red O and tube formation assays on adipose-derived stem cells (ASCs) and rat aortic endothelial cells (RAECs), respectively. In vivo, saline or ATE was injected into the adipose tissue engineering chamber 1 week after its implantation. At different time points post-injection, the contents were morphometrically, histologically, and immunohistochemically evaluated, and the expression of growth factors and adipogenic genes was analyzed by enzyme-linked immunosorbent assay (ELISA) and quantitative real-time PCR. With the exception of the baseline control group, in which fat flaps were not inserted into a chamber, the total volume of fat flap tissue increased significantly in all groups, especially in the ATE group. Better morphology and structure, a thinner capsule, and more vessels were observed in the ATE group than in the control group. Expression of angiogenic growth factors and adipogenic markers were significantly higher in the ATE group. ATE therefore significantly promoted adipose tissue regeneration and reduced capsule formation in an adipose tissue engineering chamber model. These data suggest that ATE provides a more angiogenic and adipogenic microenvironment for adipose tissue formation by releasing various cytokines and growth factors that also inhibit capsule formation. PMID:26678825

  11. QCM-D and ToF-SIMS Investigation to Deconvolute the Relationship between Lipid Adsorption and Orientation on Lipase Activity.

    Joyce, Paul; Kempson, Ivan; Prestidge, Clive A

    2015-09-22

    Quartz crystal microbalance with dissipation (QCM-D) and time-of-flight secondary ion mass spectrometry (ToF-SIMS) were used to provide insights into the relationship between lipid adsorption kinetics and molecular behavior in porous silica particles of varying hydrophobicities on lipase activity. Lipase (an interfacial enzyme that cleaves ester bonds to break down lipids to fatty acids and monoglycerides) activity was controlled by loading triglycerides at different surface coverages in hydrophilic and hydrophobic porous silica particles. The rate of lipid adsorption increased 2-fold for the hydrophobic surface compared to the hydrophilic surface. However, for submonolayer lipid coverage, the hydrophilic surface enhanced lipase activity 4-fold, whereas the hydrophobic surface inhibited lipase activity 16-fold, compared to lipid droplets in water. A difference in lipid orientation for low surface coverage, evidenced by ToF-SIMS, indicated that lipid adsorbs to hydrophilic silica in a conformation promoting hydrolysis. Multilayer coverage on hydrophobic and hydrophilic surfaces was indistinguishable with ToF-SIMS analysis. Increased lipid adsorption for both substrates facilitated digestion kinetics comparable to a conventional emulsion. Improved understanding of the interfacial adsorption and orientation of lipid and its digestibility in porous silica has implications in improving the uptake of pharmaceuticals and nutrients from lipid-based delivery systems. PMID:26340506

  12. Lipoprotein lipase activity and mass, apolipoprotein C-II mass and polymorphisms of apolipoproteins E and A5 in subjects with prior acute hypertriglyceridaemic pancreatitis

    García-Arias Carlota

    2009-06-01

    Full Text Available Abstract Background Severe hypertriglyceridaemia due to chylomicronemia may trigger an acute pancreatitis. However, the basic underlying mechanism is usually not well understood. We decided to analyze some proteins involved in the catabolism of triglyceride-rich lipoproteins in patients with severe hypertriglyceridaemia. Methods Twenty-four survivors of acute hypertriglyceridaemic pancreatitis (cases and 31 patients with severe hypertriglyceridaemia (controls were included. Clinical and anthropometrical data, chylomicronaemia, lipoprotein profile, postheparin lipoprotein lipase mass and activity, hepatic lipase activity, apolipoprotein C II and CIII mass, apo E and A5 polymorphisms were assessed. Results Only five cases were found to have LPL mass and activity deficiency, all of them thin and having the first episode in childhood. No cases had apolipoprotein CII deficiency. No significant differences were found between the non-deficient LPL cases and the controls in terms of obesity, diabetes, alcohol consumption, drug therapy, gender distribution, evidence of fasting chylomicronaemia, lipid levels, LPL activity and mass, hepatic lipase activity, CII and CIII mass or apo E polymorphisms. However, the SNP S19W of apo A5 tended to be more prevalent in cases than controls (40% vs. 23%, NS. Conclusion Primary defects in LPL and C-II are rare in survivors of acute hypertriglyceridaemic pancreatitis; lipase activity measurements should be restricted to those having their first episode during chilhood.

  13. Concentration, partial characterization, and immobilization of lipase extract from P. brevicompactum by solid-state fermentation of babassu cake and castor bean cake.

    Silva, Marceli Fernandes; Freire, Denise M G; de Castro, Aline Machado; Di Luccio, Marco; Mazutti, Marcio A; Oliveira, J Vladimir; Treichel, Helen; de Oliveira, Débora

    2011-07-01

    One relevant limitation hindering the industrial application of microbial lipases has been attributed to their production cost, which is determined by the production yield, enzyme stability among other. The objective of this work was to evaluate the concentration and immobilization of lipase extracts from Penicillium brevicompactum obtained by solid-state fermentation of babassu cake and castor bean cake. The precipitation with ammonium sulfate 60% of saturation of crude extract obtained with babassu cake as raw material showed an enhancement in hydrolytic and esterification activities from 31.82 to 227.57 U/g and from 170.92 to 207.40 U/g, respectively. Concentrated lipase extracts showed preference to medium-chain triglycerides and fatty acids. It is shown that the enzyme activity is maintained during storage at low temperatures (4 and -10°C) for up to 30 days. Higher esterification activities were achieved when the lipase extract was immobilized in sodium alginate and activated coal. PMID:21258873

  14. Defective differentiation of adipose precursor cells from lipodystrophic mice lacking perilipin 1.

    Ying Lyu

    Full Text Available Perilipin 1 (Plin1 localizes at the surface of lipid droplets to regulate triglyceride storage and hydrolysis in adipocytes. Plin1 defect leads to low adiposity in mice and partial lipodystrophy in human. This study investigated the roles of Plin1 in adipocyte differentiation. Plin1 null (-/- mice showed plenty of multilocular adipocytes and small unilocular adipocytes in adipose tissue, along with lack of a subpopulation of adipose progenitor cells capable of in vivo adipogenesis and along with downregulation of adipogenic pathway. Before initiation of differentiation, adipose stromal-vascular cells (SVCs from Plin1-/- mice already accumulated numerous tiny lipid droplets, which increased in number and size during the first 12-h induction but thereafter became disappeared at day 1 of differentiation. The adipogenic signaling was dysregulated despite protein level of PPARγ was near normal in Plin1-/- SVCs like in Plin1-/- adipose tissue. Heterozygous Plin1+/- SVCs were able to develop lipid droplets, with both the number and size more than in Plin1-/- SVCs but less than in Plin1+/+ SVCs, indicating that Plin1 haploinsufficiency accounts for attenuated adipogenesis. Aberrant lipid droplet growth and differentiation of Plin1-/- SVCs were rescued by adenoviral Plin1 expression and were ameliorated by enhanced or prolonged adipogenic stimulation. Our finding suggests that Plin1 plays an important role in adipocyte differentiation and provides an insight into the pathology of partial lipodystrophy in patients with Plin1 mutation.

  15. Lipase as a marker enzyme for bioassays

    The detection of various biochemical analytes is usually carried out after the biorecognition with labeled molecules. The most common label is still the radioactivity. However, the short half-life and health hazard of the radionuclides make the non-radioactive labels more popular. The fluorescence and chemiluminescence markers allow direct measurements, but they are not as sensitive as the enzymatic labels. Enzyme labels are the most sensitive non-radioactive markers and in combination with suitable colorimetric or chemiluminescence substrates the same detection limits as with radioactivity can be achieved. Direct enzyme markers offer not only a high sensitivity, but also a low background and non problematic and fast detection. The most commonly used enzymatic labels are horse-radish peroxidase and the alkaline phosphatase. In this work a new enzymatic label, lipase from Candida rugosa, was introduced. This 60 kDa large protein from the group of hydrolases is more active then the commercially available enzymes. In this thesis the most important characteristics of the lipase were characterized: specific activity, substrate specificity, temperature stability, pH optimum, storage stability and influence of detergents an the protein. The lipase was used for the labeling of short oligonucleotides (20-30 nucleotides long). The labeling was carried out through a terminal pending reactive group not to prevent the formation of hybrids during the hybridization process. The hybridization with labeled oligonucleotides is a fast process in comparison to the hybridization with long nucleic acids. This process takes place in simple working solutions at relatively low temperatures. Under these condition lipase remains active and stable, which leads to high signals. According to the high stability of lipase under working conditions, wide pH optimum and extreme high specific activity in comparison to the commonly used enzyme labels make it possible to open new perspectives for

  16. Efficient biocatalyst by encapsulating lipase into nanoporous gold

    Du, Xiaoyu; Liu, Xueying; Li, Yufei; Wu, Chao; Wang, Xia; Xu, Ping

    2013-04-01

    Lipases are one of the most important biocatalysts for biotechnological applications. Immobilization is an efficient method to increase the stability and reusability of lipases. In this study, nanoporous gold (NPG), a new kind of nanoporous material with tunable porosity and excellent biocompatibility, was employed as an effective support for lipase immobilization. The pore size of NPG and adsorption time played key roles in the construction of lipase-NPG biocomposites. The morphology and composition of NPG before and after lipase loading are verified using a scanning electron microscope, equipped with an energy-dispersive X-ray spectrometer. The resulting lipase-NPG biocomposites exhibited excellent catalytic activity and remarkable reusability. The catalytic activity of the lipase-NPG biocomposite with a pore size of 35 nm had no decrease after ten recycles. Besides, the lipase-NPG biocomposite exhibited high catalytic activity in a broader pH range and higher temperature than that of free lipase. In addition, the leaching of lipase from NPG could be prevented by matching the protein's diameter and pore size. Thus, the encapsulation of enzymes within NPG is quite useful for establishing new functions and will have wide applications for different chemical processes.

  17. Development and differentiation of adipose tissue

    Ivković-Lazar Tatjana A.

    2003-01-01

    Introduction For years adipose tissue has been considered inert, serving only as a depot of energy surplus. However, there have been recent changes, undoubtedly due to advancement of methods for studying the morphology and metabolic activities of adipose tissue (microdialysis and adipose tissue catheterization). In normal-weight subjects, adipose tissue makes 10-12% with males and 15-20% with females. About 80 % of adipose tissue is located under the skin, and the rest envelops the internal o...

  18. Development of a chemically defined serum-free medium for differentiation of rat adipose precursor cells

    Stromal-vascular cells from the epididymal fat pad of 4-week-old rats, when cultured in a medium containing insulin or insulin-like growth factor, IFG-I, triiodothyronine and transferrin, were able to undergo adipose conversion. Over ninety percent of the cells accumulated lipid droplets and this proportion was reduced in serum-supplemented medium. The adipose conversion was assessed by the development of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH) activities, [14]glucose incorporation into polar and neutral lipids, triacylglycerol accumulation and lipolysis in response to isoproterenol. Similar results were obtained with stromal-vascular cells from rat subcutaneous and retroperitoneal adipose tissues. Stromal-vascular cells required no adipogenic factors in addition to the components of the serum-free medium. Insulin was required within a physiological range of concentrations for the emergence of LPL and at higher concentrations for that of GPDH. When present at concentrations ranging from 2 to 50 nM, IGF-I was able to replace insulin for the expression of both LPL and and GPDH. The development of a serum free, chemically defined medium for the differentiation of diploid adiopose precursor cells opens up the possibility of characterizing inhibitors or activators of the adipose conversion process

  19. Development of a chemically defined serum-free medium for differentiation of rat adipose precursor cells

    Deslex, S.; Negrel, R.; Ailhaud, G.

    1987-01-01

    Stromal-vascular cells from the epididymal fat pad of 4-week-old rats, when cultured in a medium containing insulin or insulin-like growth factor, IFG-I, triiodothyronine and transferrin, were able to undergo adipose conversion. Over ninety percent of the cells accumulated lipid droplets and this proportion was reduced in serum-supplemented medium. The adipose conversion was assessed by the development of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH) activities, (/sup 14/)glucose incorporation into polar and neutral lipids, triacylglycerol accumulation and lipolysis in response to isoproterenol. Similar results were obtained with stromal-vascular cells from rat subcutaneous and retroperitoneal adipose tissues. Stromal-vascular cells required no adipogenic factors in addition to the components of the serum-free medium. Insulin was required within a physiological range of concentrations for the emergence of LPL and at higher concentrations for that of GPDH. When present at concentrations ranging from 2 to 50 nM, IGF-I was able to replace insulin for the expression of both LPL and and GPDH. The development of a serum free, chemically defined medium for the differentiation of diploid adiopose precursor cells opens up the possibility of characterizing inhibitors or activators of the adipose conversion process.

  20. Enzyme Hydrolysis of Triglycerides in Segmented Flow Microdevices

    Čech, J.; Slouka, Z.; Schrott, W.; Přibyl, M.; Kuncová, Gabriela

    Praha: Process Engineering Publisher, 2010, s. 1739. ISBN 978-80-02-02250-3. [International Congress of Chemical and Process Engineering CHISA 2010 and 7th European Congress of Chemical Engineering ECCE-7 /19./. Prague (CZ), 28.08.2010-01.09.2010] Institutional research plan: CEZ:AV0Z40720504 Keywords : microcapillary/microchannel reaction * microdevices * lipase Subject RIV: CE - Biochemistry www.chisa.cz/2010, www.ecce7.com

  1. Alipogene tiparvovec: a review of its use in adults with familial lipoprotein lipase deficiency.

    Scott, Lesley J

    2015-02-01

    Alipogene tiparvovec (Glybera®; AMT-011, AAV1-LPL(S447X)) is an adeno-associated virus serotype 1-based gene therapy for adult patients with familial lipoprotein lipase (LPL) deficiency (LPLD) and suffering from severe or multiple pancreatitis attacks despite dietary fat restrictions. It is administered as a one-time series of intramuscular injections in the legs. LPLD, a rare autosomal recessive disorder, results in hyperchylomicronaemia and severe hypertriglyceridaemia, which in turn, are associated with an increased risk of clinical complications, the most debilitating of which is recurrent severe and potentially life-threatening pancreatitis. In clinical studies (n = 27 patients), one-time administration of alipogene tiparvovec was associated with significant reductions in plasma triglyceride levels during the 12 or 14 week study period post administration. Although triglyceride levels returned to pre-treatment levels within 16-26 weeks after administration, patients had sustained improvements in postprandial chylomicron metabolism, with sustained expression of functional copies of the LPL (S477X) gene and of biologically active LPL in skeletal muscle. Moreover, after up to 6 years' follow-up post administration, there were clinically relevant reductions in the incidence of documented pancreatitis and acute abdominal pain events consistent with pancreatitis. Alipogene tiparvovec was generally well tolerated, with most adverse events being localized, transient, mild to moderate injection-site reactions. This article reviews the pharmacology of alipogene tiparvovec and its efficacy and safety in adults with LPLD. PMID:25559420

  2. Insulin Regulates Hepatic Triglyceride Secretion and Lipid Content via Signaling in the Brain.

    Scherer, Thomas; Lindtner, Claudia; O'Hare, James; Hackl, Martina; Zielinski, Elizabeth; Freudenthaler, Angelika; Baumgartner-Parzer, Sabina; Tödter, Klaus; Heeren, Joerg; Krššák, Martin; Scheja, Ludger; Fürnsinn, Clemens; Buettner, Christoph

    2016-06-01

    Hepatic steatosis is common in obesity and insulin resistance and results from a net retention of lipids in the liver. A key mechanism to prevent steatosis is to increase secretion of triglycerides (TG) packaged as VLDLs. Insulin controls nutrient partitioning via signaling through its cognate receptor in peripheral target organs such as liver, muscle, and adipose tissue and via signaling in the central nervous system (CNS) to orchestrate organ cross talk. While hepatic insulin signaling is known to suppress VLDL production from the liver, it is unknown whether brain insulin signaling independently regulates hepatic VLDL secretion. Here, we show that in conscious, unrestrained male Sprague Dawley rats the infusion of insulin into the third ventricle acutely increased hepatic TG secretion. Chronic infusion of insulin into the CNS via osmotic minipumps reduced the hepatic lipid content as assessed by noninvasive (1)H-MRS and lipid profiling independent of changes in hepatic de novo lipogenesis and food intake. In mice that lack the insulin receptor in the brain, hepatic TG secretion was reduced compared with wild-type littermate controls. These studies identify brain insulin as an important permissive factor in hepatic VLDL secretion that protects against hepatic steatosis. PMID:26861781

  3. Immobilization of Yarrowia lipolytica Lipase on Macroporous Resin Using Different Methods: Characterization of the Biocatalysts in Hydrolysis Reaction

    2015-01-01

    To improve the reusability and organic solvent tolerance of microbial lipase and expand the application of lipase (hydrolysis, esterification, and transesterification), we immobilized marine microbial lipase using different methods and determined the properties of immobilized lipases. Considering the activity and cost of immobilized lipase, the concentration of lipase was fixed at 2 mg/mL. The optimal temperature of immobilized lipases was 40°C and 5°C higher than free lipase. The activities ...

  4. Echocardiographic Assessment of Epicardial Adipose Tissue - A Marker of Visceral Adiposity

    Singh, Navneet; Singh, Harleen; Khanijoun, Harleen K; Iacobellis, Gianluca

    2007-01-01

    Visceral adipose tissue predicts an unfavorable cardiovascular and metabolic risk profile in humans. Existing methods to assess visceral adipose tissue have been limited. Thus, echocardiographic assessment of epicardial adipose tissue as a marker of visceral adiposity was suggested. The technique has been shown to be a very reliable method and an excellent measure of visceral adiposity. In this article, epicardial adipose tissue’s localization on the heart, function, method of assessment and ...

  5. Up-regulation of mitochondrial activity and acquirement of brown adipose tissue-like property in the white adipose tissue of fsp27 deficient mice.

    Shen Yon Toh

    Full Text Available Fsp27, a member of the Cide family proteins, was shown to localize to lipid droplet and promote lipid storage in adipocytes. We aimed to understand the biological role of Fsp27 in regulating adipose tissue differentiation, insulin sensitivity and energy balance. Fsp27(-/- mice and Fsp27/lep double deficient mice were generated and we examined the adiposity, whole body metabolism, BAT and WAT morphology, insulin sensitivity, mitochondrial activity, and gene expression changes in these mouse strains. Furthermore, we isolated mouse embryonic fibroblasts (MEFs from wildtype and Fsp27(-/- mice, followed by their differentiation into adipocytes in vitro. We found that Fsp27 is expressed in both brown adipose tissue (BAT and white adipose tissue (WAT and its levels were significantly elevated in the WAT and liver of leptin-deficient ob/ob mice. Fsp27(-/- mice had increased energy expenditure, lower levels of plasma triglycerides and free fatty acids. Furthermore, Fsp27(-/-and Fsp27/lep double-deficient mice are resistant to diet-induced obesity and display increased insulin sensitivity. Moreover, white adipocytes in Fsp27(-/- mice have reduced triglycerides accumulation and smaller lipid droplets, while levels of mitochondrial proteins, mitochondrial size and activity are dramatically increased. We further demonstrated that BAT-specific genes and key metabolic controlling factors such as FoxC2, PPAR and PGC1alpha were all markedly upregulated. In contrast, factors inhibiting BAT differentiation such as Rb, p107 and RIP140 were down-regulated in the WAT of Fsp27(-/- mice. Remarkably, Fsp27(-/- MEFs differentiated in vitro show many brown adipocyte characteristics in the presence of the thyroid hormone triiodothyronine (T3. Our data thus suggest that Fsp27 acts as a novel regulator in vivo to control WAT identity, mitochondrial activity and insulin sensitivity.

  6. Gastric lipase: localization of the enzyme in the stomach

    Isolated gastric glands prepared from human and rabbit stomach secrete lipase in response to secretagogues. They have investigated the localization of this enzyme in three species (rabbit, baboon, guinea pig). Gastric mucosa was sampled from the cardia (C), fundus-smooth (FS), fundus-ruggae (FR) and the antral area (A). Lipase activity was measured in mucosal homogenates using 3H-triolein as substrate and is expressed in units (U) = nmols free fatty acid released/min/mg wet weight. The localization of lipase is compared with that of pepsin (measured by hydrolysis of 2% hemoglobin at pH 1.8 and expressed in I.U.). Lipase is localized in a well defined area in the rabbit and is diffusely distributed in both guinea pig and baboon. The distribution of lipase and pepsin containing cells differs in all three species. The cellular origin of gastric lipase remains to be determined

  7. Screening for lipase activity in the oil palm.

    Sambanthamurthi, R; Rajanaidu, N; Hasnah Parman, S

    2000-12-01

    The oil palm mesocarp contains an endogenous lipase which is strongly activated at low temperature. Lipase activity is thus very conveniently assayed by prior exposure of the fruits to low temperature. More than 100 oil palm samples from the germplasm collection of the Palm Oil Research Institute of Malaysia (now known as the Malaysian Palm Oil Board) were screened for non-esterified fatty acid activity using both the low-temperature activation assay and a radioactivity assay. The results showed good correlation between assay procedures. The different samples had a very wide range of lipase activity. Elaeis oleifera samples had significantly lower lipase activity compared with E. guineensis (var. tenera) samples. Even within E. guineensis (var. tenera), there was a wide range of activity. The results confirmed that lipase activity is genotype-dependent. Selection for lipase genotypes is thus possible and this will have obvious commercial value. PMID:11171201

  8. Rat liver contains a limited number of binding sites for hepatic lipase

    Schoonderwoerd, Kees; Verhoeven, Adrie; Jansen, Hans

    1994-01-01

    textabstractThe binding of hepatic lipase to rat liver was studied in an ex vivo perfusion model. The livers were perfused with media containing partially purified rat hepatic lipase or bovine milk lipoprotein lipase. The activity of the enzymes was determined in the perfusion media before and after passage through the liver. During perfusion with a hepatic-lipase-containing medium the lipase activity in the medium did not change, indicating that there was no net binding of lipase by the live...

  9. Molecular characterization of a proteolysis-resistant lipase from Bacillus pumilus SG2

    Sangeetha, R.; Arulpandi, I.; A Geetha

    2014-01-01

    Proteolysis-resistant lipases can be well exploited by industrial processes which employ both lipase and protease as biocatalysts. A proteolysis resistant lipase from Bacillus pumilus SG2 was isolated, purified and characterized earlier. The lipase was resistant to native and commercial proteases. In the present work, we have characterized the lip gene which encodes the proteolysis-resistant lipase from Bacillus pumilus SG2. The parameters and structural details of lipase were analysed. The l...

  10. Bioengineering Beige Adipose Tissue Therapeutics

    Tharp, Kevin M; Stahl, Andreas

    2015-01-01

    Unlocking the therapeutic potential of brown/beige adipose tissue requires technological advancements that enable the controlled expansion of this uniquely thermogenic tissue. Transplantation of brown fat in small animal model systems has confirmed the expectation that brown fat expansion could possibly provide a novel therapeutic to combat obesity and related disorders. Expansion and/or stimulation of uncoupling protein-1 (UCP1)-positive adipose tissues have repeatedly demonstrated physiolog...

  11. Adipogenic differentiation state-specific gene expression as related to bovine carcass adiposity.

    Pickworth, C L; Loerch, S C; Velleman, S G; Pate, J L; Poole, D H; Fluharty, F L

    2011-02-01

    Genetic regulation of the site of fat deposition is not well defined. The objective of this study was to investigate adipogenic differentiation state-specific gene expression in feedlot cattle (>75% Angus; Simmental parentage) of varying adipose accretion patterns. Four groups of 4 steers were selected via ultrasound for the following adipose tissue characteristics: low subcutaneous-low intramuscular (LSQ-LIM), low subcutaneous-high intramuscular (LSQ-HIM), high subcutaneous-low intramuscular (HSQ-LIM), and high subcutaneous-high intramuscular (HSQ-HIM). Adipose tissue from the subcutaneous (SQ) and intramuscular (IM) depots was collected at slaughter. The relative expression of adipogenic genes was evaluated using quantitative PCR. Data were analyzed using the mixed model of SAS, and gene expression data were analyzed using covariate analysis with ribosomal protein L19 as the covariate. No interactions (P > 0.10) were observed between IM and SQ adipose tissue depots for any of the variables measured. Therefore, only the main effects of high and low accretion within a depot and the effects of depot are reported. Steers with LIM had smaller mean diameter IM adipocytes (P 0.10) in any of the genes measured due to high or low adipose accretion. Preadipogenic delta-like kinase1 mRNA was greater in the IM than the SQ adipose tissue; conversely, differentiating and adipogenic genes, lipoprotein lipase, PPARγ, fatty acid synthetase, and fatty acid binding protein 4 were greater (P < 0.001) in the SQ than the IM depot. Intramuscular adipocytes were smaller than SQ adipocytes and had greater expression of the preadipogenic gene, indicating that more hyperplasia was occurring. Meanwhile, SQ adipose tissue contained much larger (P < 0.001) adipocytes that had a greater expression (P < 0.001) of differentiating and adipogenic genes than did the IM adipose tissue, indicating more cells were undergoing differentiation and hypertrophy. Adipogenic differentiation state

  12. Enhancement of red blood cell aggregation by plasma triglycerides.

    Cicha, I; Suzuki, Y; Tateishi, N; Maeda, N

    2001-01-01

    The effects of plasma triglycerides level on human red blood cells (RBCs) indices, hematological parameters, RBCs aggregation velocity and whole blood viscosity were studied at 2 hours after high-fat or low-fat meal. Proteins, triglycerides and cholesterol levels of plasma were analysed. The RBCs rouleaux formation rate was measured in 70% autologous plasma (with 30% phosphate-buffered saline, PBS) or 1 g/dl dextran T70 solution (with 4 g/dl bovine serum albumin) in PBS, using a low-shear rheoscope. The results were grouped according to triglycerides content in plasma. No significant difference in whole blood viscosity, hematological parameters, RBC indices, protein and cholesterol content was observed between high-fat and low-fat blood samples. There was a significant increase in rouleaux formation rate of samples with high triglyceride levels, when measured in 70% autologous plasma, but it was not significant in dextran T70 containing medium. In conclusion, the results obtained suggest that alteration of plasma lipid levels as well as possible changes in the cell membrane lipid composition lead to enhanced RBC aggregation. PMID:11564913

  13. Triglyceride in plasma: prospective effects on microcirculatory functions.

    Maeda, Nobuji; Cicha, Iwona; Tateishi, Norihiko; Suzuki, Yoji

    2006-01-01

    The effect of triglyceride in plasma on RBC aggregation was examined, and the prospective influence on the flow of RBCs in microcirculation and the O2 release was discussed. To minimize the individual differences, blood samples were collected from one subject 2 hrs after high-fat and low fat meals. Triglyceride content in plasma was measured by an enzymatic method, and the rate of rouleaux formation was measured with a low shear rheoscope. The rate of rouleaux formation was increased with the increase of triglyceride concentration. Our previous findings suggested some functional impairment in microcirculation. (1) The enhanced RBC aggregation tends to reduce flow resistance in arterioles, but results in inhomogeneous flow of RBCs in capillaries. (2) The sclerotic change of microvessels alters flow behavior of RBCs, and thereby flow resistance is increased. (3) The enhanced RBC aggregation reduces O2 release from RBCs flowing in microvessels. In conclusion, high triglyceride level in plasma not only changes flow behavior of RBCs in microcirculation and thus increases flow resistance, but also prevents homogeneous tissue oxygenation. PMID:16543655

  14. Release of endothelial cell lipoprotein lipase by plasma lipoproteins and free fatty acids

    Lipoprotein lipase (LPL) bound to the lumenal surface of vascular endothelial cells is responsible for the hydrolysis of triglycerides in plasma lipoproteins. Studies were performed to investigate whether human plasma lipoproteins and/or free fatty acids would release LPL which was bound to endothelial cells. Purified bovine milk LPL was incubated with cultured porcine aortic endothelial cells resulting in the association of enzyme activity with the cells. When the cells were then incubated with media containing chylomicrons or very low density lipoproteins (VLDL), a concentration-dependent decrease in the cell-associated LPL enzymatic activity was observed. In contrast, incubation with media containing low density lipoproteins or high density lipoproteins produced a much smaller decrease in the cell-associated enzymatic activity. The addition of increasing molar ratios of oleic acid:bovine serum albumin to the media also reduced enzyme activity associated with the endothelial cells. To determine whether the decrease in LPL activity was due to release of the enzyme from the cells or inactivation of the enzyme, studies were performed utilizing radioiodinated bovine LPL. Radiolabeled LPL protein was released from endothelial cells by chylomicrons, VLDL, and by free fatty acids (i.e. oleic acid bound to bovine serum albumin). The release of radiolabeled LPL by VLDL correlated with the generation of free fatty acids from the hydrolysis of VLDL triglyceride by LPL bound to the cells. Inhibition of LPL enzymatic activity by use of a specific monoclonal antibody, reduced the extent of release of 125I-LPL from the endothelial cells by the added VLDL. These results demonstrated that LPL enzymatic activity and protein were removed from endothelial cells by triglyceride-rich lipoproteins (chylomicrons and VLDL) and oleic acid

  15. Associations of Lipoprotein Lipase Gene rs326 with Changes of Lipid Profiles after a High-Carbohydrate and Low-Fat Diet in Healthy Chinese Han Youth

    Xing-chun Zhu; Jia Lin; Qian Wang; Hui Liu; Li Qiu; Ding-zhi Fang

    2014-01-01

    To investigate the effects of a high-carbohydrate and low-fat (HC/LF) diet on plasma lipids and apolipoproteins (Apos) of healthy Chinese Han youth with different genotypes of lipoprotein lipase gene (LPL) rs326, 56 subjects were given a washout diet of 30.1% fat and 54.1% carbohydrate for seven days, followed by the HC/LF diet of 13.8% fat and 70.1% carbohydrate for six days, with no total energy restriction. Plasma glucose, triglyceride (TG), total cholesterol (TC), high density lipoprotein...

  16. Apolipoproteins C-I and C-III Inhibit Lipoprotein Lipase Activity by Displacement of the Enzyme from Lipid Droplets*

    Larsson, Mikael; Vorrsjö, Evelina; Talmud, Philippa; Lookene, Aivar; Olivecrona, Gunilla

    2013-01-01

    Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4. PMID:24121499

  17. Apolipoproteins C-I and C-III inhibit lipoprotein lipase activity by displacement of the enzyme from lipid droplets.

    Larsson, Mikael; Vorrsjö, Evelina; Talmud, Philippa; Lookene, Aivar; Olivecrona, Gunilla

    2013-11-22

    Apolipoproteins (apo) C-I and C-III are known to inhibit lipoprotein lipase (LPL) activity, but the molecular mechanisms for this remain obscure. We present evidence that either apoC-I or apoC-III, when bound to triglyceride-rich lipoproteins, prevent binding of LPL to the lipid/water interface. This results in decreased lipolytic activity of the enzyme. Site-directed mutagenesis revealed that hydrophobic amino acid residues centrally located in the apoC-III molecule are critical for attachment to lipid emulsion particles and consequently inhibition of LPL activity. Triglyceride-rich lipoproteins stabilize LPL and protect the enzyme from inactivating factors such as angiopoietin-like protein 4 (angptl4). The addition of either apoC-I or apoC-III to triglyceride-rich particles severely diminished their protective effect on LPL and rendered the enzyme more susceptible to inactivation by angptl4. These observations were seen using chylomicrons as well as the synthetic lipid emulsion Intralipid. In the presence of the LPL activator protein apoC-II, more of apoC-I or apoC-III was needed for displacement of LPL from the lipid/water interface. In conclusion, we show that apoC-I and apoC-III inhibit lipolysis by displacing LPL from lipid emulsion particles. We also propose a role for these apolipoproteins in the irreversible inactivation of LPL by factors such as angptl4. PMID:24121499

  18. Studies on the incorporation of lipase in synthetic polymerisable vesicles.

    Mosmuller, E.W.J.

    1993-01-01

    This thesis describes studies on the suitability of synthetic polymerisable vesicles for the incorporation and stabilisation of lipase for the bioconversion of organic chemical compounds.In chapter 1 , some characteristics are reviewed of hydrolytic enzymes, and more specific those of lipases. In chapter 2 an overview is presented of the features and properties of surfactants and vesicles.In chapter 3 , the incorporation is described of lipase from Candida cylindracea (CCL) into polymerisable...

  19. Seed lipases: sources, applications and properties - a review

    Barros, M; L. F. Fleuri; G. A. MACEDO

    2010-01-01

    This paper provides an overview regarding the main aspects of seed lipases, such as the reactions catalyzed, physiological functions, specificities, sources and applications. Lipases are ubiquitous in nature and are produced by several plants, animals and microorganisms. These enzymes exhibit several very interesting features, such as low cost and easy purification, which make their commercial exploitation as industrial enzymes a potentially attractive alternative. The applications of lipases...

  20. Serum immunoreactive trypsin and pancreatic lipase in primary biliary cirrhosis.

    Fonseca, V.; Epstein, O; Katrak, A; Junglee, D; Mikhailidis, D P; McIntyre, N; Dandona, P

    1986-01-01

    Immunoreactive trypsin concentration and pancreatic lipase activity were measured in the sera of 33 patients with primary biliary cirrhosis. Immunoreactive trypsin was increased (above the normal range) in 16 (48%) and pancreatic lipase activity in 18 (55%) patients. Both enzymes were increased in 10 (30%) patients. Twenty four patients (73%) had an increase of either one or both enzymes. There was a significant correlation between immunoreactive trypsin and pancreatic lipase activity. This a...

  1. Effects of Deltamethrin on Lipase Activity in Guppies (Poecilia reticulata)

    Güneş, Elif; Sedat V. Yerli

    2011-01-01

    Effect of the deltamethrin, which is extensively used synthetic pyrethroid, was investigated on the lipase activity of Poecilia reticulata in the present study. One control and five experimental groups were exposed to different concentrations of deltamethrin. Three experiments, including 60 guppies each, were conducted. Titration method was used in order to determine the lipase activity. Lipase activity level in control group was 5 U/min, while it was 2.5 U/min in the highest concentration of...

  2. Immobilization of Isolated Lipase From Moldy Copra (Aspergillus Oryzae)

    Seniwati

    2012-01-01

    Enzyme immobilization is a recovery technique that has been studied in several years, using support as a media to help enzyme dissolutions to the reaction substrate. Immobilization method used in this study was adsorption method, using specific lipase from Aspergillus oryzae. Lipase was partially purified from the culture supernatant of Aspergillus oryzae. Enzyme was immobilized by adsorbed on silica gel. Studies on free and immobilized lipase systems for determination of op...

  3. Expression of the Staphylococcus hyicus Lipase in Lactococcus lactis

    Drouault, Sophie; Corthier, Gerard; Ehrlich, S. Dusko; Renault, Pierre

    2000-01-01

    The extracellular Staphylococcus hyicus lipase was expressed under the control of different promoters in Lactococcus lactis and Bacillus subtilis. Its expression at high and moderate levels is toxic for the former and the latter hosts, respectively. In L. lactis, the lipase was expressed at a high level, up to 30% of the total cellular proteins, under the control of the inducible promoter PnisA. About 80% of the lipase remained associated with the cells. Close to half of this amount remained ...

  4. Immobilization of Isolated Lipase From Moldy Copra (Aspergillus Oryzae)

    Seniwati Dali; A. B. D. Rauf Patong; M.Noor Jalaluddin; Pirman; Baharuddin Hamzah

    2011-01-01

    Enzyme immobilization is a recovery technique that has been studied in several years, using support as a media to help enzyme dissolutions to the reaction substrate. Immobilization method used in this study was adsorption method, using specific lipase from Aspergillus oryzae. Lipase was partially purified from the culture supernatant of Aspergillus oryzae. Enzyme was immobilized by adsorbed on silica gel. Studies on free and immobilized lipase systems for determination of optimum pH, optimum ...

  5. Molecular cloning, genomic organization, and expression of a testicular isoform of hormone-sensitive lipase

    Holst, L.S.; Laurell, H.; Holm, C. [Lund Univ. (Sweden)] [and others

    1996-08-01

    By catalyzing the rate-limiting step in adipose tissue lipolysis, hormone-sensitive lipase (HSL) is an important regulator of energy homeostasis. The role and importance of HSL in tissues other than adipose are poorly understood. We report here the cloning and expression of a testicular isoform, designated HSL{sub tes}. Due to an addition of amino acids at the NH{sub 2}-termini, rat and human HSL{sub tes} consist of 1068 and 1076 amino acids, respectively, compared to the 768 and 775 amino acids, respectively, of the adipocyte isoform (HSL{sub adi}). A novel exon of 1.2 kb, encoding the human testis-specific amino acids, was isolated and mapped to the HSL gene, 16 kb upstream of the exons encoding HSL{sub adi}. The transcribed mRNA of 3.9 kb was specifically expressed in testis. No significant similarity with other known proteins was found for the testis-specific sequence. The amino acid composition differs from the HSL{sub adi} sequence, with a notable hydrophilic character and a high content of prolines and glutamines. COS cells, transfected by the 3.9-kb human testis cDNA, expressed a protein of the expected molecular mass (M{sub r} {approximately}120,000) that exhibited catalytic activity similar to that of HSL{sub adi}. Immunocytochemistry localized HSL to elongating spermatids and spermatozoa; HSL was not detected in interstitial cells. 34 refs., 5 figs.

  6. Computational Modeling of the Electrochemical System of Lipase Activity Detection

    Valdemaras Razumas

    2008-06-01

    Full Text Available This paper presents computational modeling of response kinetics of bioelectroanalytical system based on solid supported lipase substrate and lipase interaction. The model assumes that lipase substrate is formed by dripping and drying a small amount of the ethanol solution of 9-(5’-ferrocenylpentanoyloxynonyl disulfide (FPONDS and that lipase is capable of cleaving FPONDS ester bonds via hydrolysis mechanism. Two mathematical models have been developed and evaluated trough computational simulation series by comparing them to experimental data. The results of simulation demonstrate that a good fitting might be obtained only taking into account non-linear substrate wash off process.

  7. Seed lipases: sources, applications and properties - a review

    M. Barros

    2010-03-01

    Full Text Available This paper provides an overview regarding the main aspects of seed lipases, such as the reactions catalyzed, physiological functions, specificities, sources and applications. Lipases are ubiquitous in nature and are produced by several plants, animals and microorganisms. These enzymes exhibit several very interesting features, such as low cost and easy purification, which make their commercial exploitation as industrial enzymes a potentially attractive alternative. The applications of lipases in food, detergents, oils and fats, medicines and fine chemistry, effluent treatment, biodiesel production and in the cellulose pulp industry, as well as the main sources of oilseed and cereal seed lipases, are reviewed.

  8. Lipase Activity among Bacteria Isolated from Amazonian Soils

    André Luis Willerding; Luiz Antonio de Oliveira; Francisco Wesen Moreira; Mariana Gomes Germano; Aloísio Freitas Chagas

    2011-01-01

    The objective of this study was to select lipase-producing bacteria collected from different counties of the Amazon region. Of the 440 bacteria strains, 181 were selected for the lipase assay in qualitative tests at Petri dishes, being 75 (41%) lipase positive. The enzymatic index was determined during fifteen days at different temperatures (30°, 35°, 40°, and 45°C). The highest lipase activity was observed within 72 hours at 30°C. Twelve bacteria strains presented an index equal to or greate...

  9. Covalent functionalization of multi-walled carbon nanotubes by lipase

    Lipase from Candida rugosa was covalently anchored onto acid-treated multi-walled carbon nanotubes (MWNTs) through a self-catalytic mechanism. A variety of characterization techniques including FTIR, Raman spectroscopy, and XPS were employed to demonstrate the formation of the ester linkage between lipase and MWNTs. The MWNTs-lipase biocomposites showed significantly increased solubility in some common-used organic solvents, such as THF, DMF and chloroform. This study may offer a novel and facile route for covalent modification of carbon nanotubes, and expand the potential utilization of both lipases and MWNTs in the fields of biocatalyst and biosensor

  10. The value of immunoreactive lipase in acute pancreatitis.

    1988-01-01

    We have evaluated a new agglutination test for serum immunoreactive lipase in 24 patients with abdominal pain and hyperamylasaemia. On admission all 20 patients with acute pancreatitis had a positive lipase test, 3 of the 4 patients who did not have pancreatitis had a negative lipase test. The sensitivity of the lipase test on day 1 is 100%, the specificity 96% and predictive value of a positive test is 95.2% compared to 83% for amylase. A negative test excludes pancreatitis. In addition, the...

  11. Lipoprotein lipase deficiency with visceral xanthomas

    Servaes, Sabah; Bellah, Richard [Department of Radiology, Philadelphia, PA (United States); Verma, Ritu [Department of Gastroenterology, Philadelphia, PA (United States); Pawel, Bruce [Department of Pathology, Philadelphia, PA (United States)

    2010-08-15

    Lipoprotein lipase deficiency (LLD) is a rare metabolic disorder that typically presents with skin xanthomas and pancreatitis in childhood. We report a case of LLD in an infant who presented with jaundice caused by a pancreatic head mass. Abdominal imaging also incidentally revealed hyperechoic renal masses caused by renal xanthomas. This appearance of the multiple abdominal masses makes this a unique infantile presentation of LLD. (orig.)

  12. Directed evolution of an enantioselective lipase

    Liebeton, Klaus; Zonta, Albin; Schimossek, Klaus; Nardini, Marco; Lang, Dietmar; Dijkstra, Bauke W.; Reetz, Manfred T.; Jaeger, Karl-Erich

    2000-01-01

    Background: The biocatalytic production of enantiopure compounds is of steadily increasing importance to the chemical and biotechnological industry. In most cases, however, it is impossible to identify an enzyme that possesses the desired enantioselectivity. Therefore, there is a strong need to create by molecular biological methods novel enzymes which display high enantioselectivity. Results: A bacterial lipase from Pseudomonas aeruginosa (PAL) was evolved to catalyze with high enantioselect...

  13. Characterization of Cross-Linked Lipase Aggregates

    Prabhavathi Devi, Bethala Lakshmi Anu; Guo, Zheng; Xu, Xuebing

    2009-01-01

    Commercially available microbial lipases from different sources were immobilized as cross-linked enzyme aggregates (CLEAs) using different precipitants and glutaraldehyde as cross-linkers. These CLEAs were assayed based on esterification between lauric acid and n-propanol in solvent-free systems....... change upon CLEA formation. This work presents a characterization of CLEAs based on an esterification activity assay, which is useful for exploring the synthetic application potential of CLEA technology with favorable perspectives....

  14. Dietary Conjugated Linoleic Acid and Hepatic Steatosis: Species-Specific Effects on Liver and Adipose Lipid Metabolism and Gene Expression

    Diwakar Vyas

    2012-01-01

    Full Text Available Objective. To summarize the recent studies on effect of conjugated linoleic acid (CLA on hepatic steatosis and hepatic and adipose lipid metabolism highlighting the potential regulatory mechanisms. Methods. Sixty-four published experiments were summarized in which trans-10, cis-12 CLA was fed either alone or in combination with other CLA isomers to mice, rats, hamsters, and humans were compared. Summary and Conclusions. Dietary trans-10, cis-12 CLA induces a severe hepatic steatosis in mice with a more muted response in other species. Regardless of species, when hepatic steatosis was present, a concurrent decrease in body adiposity was observed, suggesting that hepatic lipid accumulation is a result of uptake of mobilized fatty acids (FA from adipose tissue and the liver's inability to sufficiently increase FA oxidation and export of synthesized triglycerides. The potential role of liver FA composition, insulin secretion and sensitivity, adipokine, and inflammatory responses are discussed as potential mechanisms behind CLA-induced hepatic steatosis.

  15. Cardiac expression of microsomal triglyceride transfer protein is increased in obesity and serves to attenuate cardiac triglyceride accumulation

    Bartels, Emil D; Nielsen, Jan M; Hellgren, Lars I;

    2009-01-01

    secretion of apolipoproteinB-containing (apoB) lipoproteins. Lipoprotein formation depends on expression of microsomal triglyceride transfer protein (MTP); the mouse expresses two isoforms of MTP, A and B. Since many aspects of the link between obesity-induced cardiac disease and cardiac lipid metabolism...

  16. FATTY-ACID COMPOSITION OF HUMAN-MILK TRIGLYCERIDE SPECIES - POSSIBLE CONSEQUENCES FOR OPTIMAL STRUCTURES OF INFANT FORMULA TRIGLYCERIDES

    WINTER, CH; HOVING, EB; MUSKIET, FAJ

    1993-01-01

    Human milk triglycerides (TGs) were separated into 14 fractions by silver ion high-performance liquid chromatography (HPLC) with light-scattering detection (LSD). Subsequent fractionation by reversed-phase HPLC-LSD resulted in 75 subfractions. The major 48 were analysed by gas chromatography for the

  17. Novel Metagenome-Derived, Cold-Adapted Alkaline Phospholipase with Superior Lipase Activity as an Intermediate between Phospholipase and Lipase

    Lee, Mi-Hwa; Oh, Ki-Hoon; Kang, Chul-Hyung; Kim, Ji-Hoon; Oh, Tae-Kwang; Ryu, Choong-Min; Yoon, Jung-Hoon

    2012-01-01

    A novel lipolytic enzyme was isolated from a metagenomic library obtained from tidal flat sediments on the Korean west coast. Its putative functional domain, designated MPlaG, showed the highest similarity to phospholipase A from Grimontia hollisae CIP 101886, though it was screened from an emulsified tricaprylin plate. Phylogenetic analysis showed that MPlaG is far from family I.6 lipases, including Staphylococcus hyicus lipase, a unique lipase which can hydrolyze phospholipids, and is more ...

  18. Potencial de biocatálise enantiosseletiva de lipases microbianas Potential of enantioselective biocatalysis by microbial lipases

    Patrícia de O. Carvalho; Silvana Ap. Calafatti; Maurício Marassi; Daniela M. da Silva; Fabiano J. Contesini; Renato Bizaco; Gabriela Alves Macedo

    2005-01-01

    Microbial lipases have a great potential for commercial applications due to their stability, selectivity and broad substrate specificity because many non-natural acids, alcohols or amines can be used as the substrate. Three microbial lipases isolated from Brazilian soil samples (Aspergillus niger; Geotrichum candidum; Penicillium solitum) were compared in terms of their stability and as biocatalysts in the enantioselective esterification using racemic substrates in organic medium. The lipase ...

  19. Biodiesel production by transesterification using immobilized lipase.

    Narwal, Sunil Kumar; Gupta, Reena

    2013-04-01

    Biodiesel can be produced by transesterification of vegetable or waste oil catalysed by lipases. Biodiesel is an alternative energy source to conventional fuel. It combines environmental friendliness with biodegradability, low toxicity and renewability. Biodiesel transesterification reactions can be broadly classified into two categories: chemical and enzymatic. The production of biodiesel using the enzymatic route eliminates the reactions catalysed under acid or alkali conditions by yielding product of very high purity. The modification of lipases can improve their stability, activity and tolerance to alcohol. The cost of lipases and the relatively slower reaction rate remain the major obstacles for enzymatic production of biodiesel. However, this problem can be solved by immobilizing the enzyme on a suitable matrix or support, which increases the chances of re-usability. The main factors affecting biodiesel production are composition of fatty acids, catalyst, solvents, molar ratio of alcohol and oil, temperature, water content, type of alcohol and reactor configuration. Optimization of these parameters is necessary to reduce the cost of biodiesel production. PMID:23247566

  20. Alkaline lipase of glyoxysomes is a glycoprotein

    In castor bean endosperm, the glyoxysomal alkaline lipase is an intrinsic membrane protein. At four days post-germination, the enzyme is also present in the endoplasmic reticulum where it accounts for approximately 15% of total activity. The active enzyme was purified by Maeshima and Beevers from isolated glyoxysomes. Specific antibodies to the 62 kD subunit were raised in rabbits. The anti-lipase has been used in preliminary experiments to determine the relationship between the lipase of the glyoxysomal membrane and the ER. Results indicate the presence of 3 cross-reacting antigens in carbonate-washed ER and glyoxysomal membranes. The 62 kD subunit, found predominantly in glyoxysomes, was eluted form Con-A Sepharose by 0.5 M α-methylglucoside. An 86kD form present in 2-d ER (but not in 4-d ER) and glyoxysomes did not bind Con-A Sepharose. This form appears to be an unglycosylated precursor or the 62 kD subunit. A 67 kD form was the only species seen in 4-d ER. In a time course experiment, the 67 kD form appeared on the glyoxysomal membrane

  1. Adiposity and Glycemic Control in Children Exposed to Perfluorinated Compounds

    Timmermann, Clara Amalie G.; Rossing, Laura I.; Grontved, Anders;

    2014-01-01

    perfluorooctane sulfonic acid/mL plasma was associated with 16.2% (95% confidence interval [CI], 5.2%-28.3%) higher insulin concentration, 12.0% (95% CI, 2.4%-22.4%) higher β-cell activity, 17.6% (95% CI, 5.8%-30.8%) higher insulin resistance, and 8.6% (95% CI, 1.2%-16.5%) higher triglyceride concentrations, and...... an increase of 10 ng perfluorooctanoic acid/mL plasma was associated with 71.6% (95% CI, 2.4%-187.5%) higher insulin concentration, 67.5% (95% CI, 5.5%-166.0%) higher β-cell function, 73.9% (95% CI, 0.2%-202.0%) higher insulin resistance, and 76.2% (95% CI, 22.8%-153.0%) higher triglyceride......Objective: Our objective was to explore whether childhood exposure to perfluorinated and polyfluorinated compounds (PFCs), widely used stain- and grease-repellent chemicals, is associated with adiposity and markers of glycemic control. Materials and Methods: Body mass index, skinfold thickness...

  2. Lipase immobilization and production of fatty acid methyl esters from canola oil using immobilized lipase

    Lipase enzyme from Aspergillus oryzae (EC 3.1.1.3) was immobilized onto a micro porous polymeric matrix which contains aldehyde functional groups and methyl esters of long chain fatty acids (biodiesel) were synthesized by transesterification of crude canola oil using immobilized lipase. Micro porous polymeric matrix was synthesized from styrene-divinylbenzene (STY-DVB) copolymers by using high internal phase emulsion technique and two different lipases, Lipozyme TL-100L® and Novozym 388®, were used for immobilization by both physical adsorption and covalent attachment. Biodiesel production was carried out with semi-continuous operation. Methanol was added into the reactor by three successive additions of 1:4 M equivalent of methanol to avoid enzyme inhibition. The transesterification reaction conditions were as follows: oil/alcohol molar ratio 1:4; temperature 40 oC and total reaction time 6 h. Lipozyme TL-100L® lipase provided the highest yield of fatty acid methyl esters as 92%. Operational stability was determined with immobilized lipase and it indicated that a small enzyme deactivation occurred after used repeatedly for 10 consecutive batches with each of 24 h. Since the process is yet effective and enzyme does not leak out from the polymer, the method can be proposed for industrial applications. -- Research highlights: → Lipozyme TL-100L and Novozym 388 were immobilized onto micro porous polymeric matrix by both physical adsorption and covalent linking. → Immobilized enzymes were used for synthesis of fatty acid methyl esters by transesterification of canola oil and methanol using semi-continuous operation system. → According to chromatographic analysis, Lipase Lipozyme TL-100L resulted in the highest yield of methyl ester as 92%.

  3. Immobilization of a Commercial Lipase from Penicillium camembertii (Lipase G by Different Strategies

    Adriano A. Mendes

    2011-01-01

    Full Text Available The objective of this work was to select the most suitable procedure to immobilize lipase from Penicillium camembertii (Lipase G. Different techniques and supports were evaluated, including physical adsorption on hydrophobic supports octyl-agarose, poly(hydroxybutyrate and Amberlite resin XAD-4; ionic adsorption on the anionic exchange resin MANAE-agarose and covalent attachment on glyoxyl-agarose, MANAE-agarose cross-linked with glutaraldehyde, MANAE-agarose-glutaraldehyde, and epoxy-silica-polyvinyl alcohol composite. Among the tested protocols, the highest hydrolytic activity (128.2 ± 8.10 IU·g−1 of support was achieved when the lipase was immobilized on epoxy-SiO2-PVA using hexane as coupling medium. Lipase immobilized by ionic adsorption on MANAE-agarose also gave satisfactory result, attaining 55.6 ± 2.60 IU·g−1 of support. In this procedure, the maximum loading of immobilized enzyme was 9.3 mg·g−1 of gel, and the highest activity (68.8 ± 2.70 IU·g−1 of support was obtained when 20 mg of protein·g−1 was offered. Immobilization carried out in aqueous medium by physical adsorption on hydrophobic supports and covalent attachment on MANAE-agarose-glutaraldehyde and glyoxyl-agarose was shown to be unfeasible for Lipase G. Thermal stability tests revealed that the immobilized derivative on epoxy-SiO2-PVA composite using hexane as coupling medium had a slight higher thermal stability than the free lipase.

  4. Immobilization of a Commercial Lipase from Penicillium camembertii (Lipase G) by Different Strategies.

    Mendes, Adriano A; Freitas, Larissa; de Carvalho, Ana Karine F; de Oliveira, Pedro C; de Castro, Heizir F

    2011-01-01

    The objective of this work was to select the most suitable procedure to immobilize lipase from Penicillium camembertii (Lipase G). Different techniques and supports were evaluated, including physical adsorption on hydrophobic supports octyl-agarose, poly(hydroxybutyrate) and Amberlite resin XAD-4; ionic adsorption on the anionic exchange resin MANAE-agarose and covalent attachment on glyoxyl-agarose, MANAE-agarose cross-linked with glutaraldehyde, MANAE-agarose-glutaraldehyde, and epoxy-silica-polyvinyl alcohol composite. Among the tested protocols, the highest hydrolytic activity (128.2 ± 8.10 IU·g(-1) of support) was achieved when the lipase was immobilized on epoxy-SiO(2)-PVA using hexane as coupling medium. Lipase immobilized by ionic adsorption on MANAE-agarose also gave satisfactory result, attaining 55.6 ± 2.60 IU·g(-1) of support. In this procedure, the maximum loading of immobilized enzyme was 9.3 mg·g(-1) of gel, and the highest activity (68.8 ± 2.70 IU·g(-1) of support) was obtained when 20 mg of protein·g(-1) was offered. Immobilization carried out in aqueous medium by physical adsorption on hydrophobic supports and covalent attachment on MANAE-agarose-glutaraldehyde and glyoxyl-agarose was shown to be unfeasible for Lipase G. Thermal stability tests revealed that the immobilized derivative on epoxy-SiO(2)-PVA composite using hexane as coupling medium had a slight higher thermal stability than the free lipase. PMID:21811674

  5. Homologous Expression of the Lipase and ABC Transporter Gene Cluster, tliDEFA, Enhances Lipase Secretion in Pseudomonas spp.

    Ahn, Jung Hoon; Pan, Jae Gu; Rhee, Joon Shick

    2001-01-01

    The ABC transporter TliDEF was found to be an efficient secretory apparatus for extracellular lipase TliA in Pseudomonas fluorescens. For the enhanced secretion of the lipase, we tried to coexpress tliA and tliDEF in various Pseudomonas species. Whereas the coexpression of tliA and tliDEF was required for the lipase secretion in P. fragi, the expression of tliA was sufficient for the lipase secretion in P. fluorescens, P. syringae, and P. putida, indicating the existence of compatible ABC tra...

  6. Adipose tissues and thyroid hormones

    Maria-Jesus eObregon

    2014-12-01

    Full Text Available The maintenance of energy balance is regulated by complex homeostatic mechanisms, including those emanating from adipose tissue. The main function of the adipose tissue is to store the excess of metabolic energy in the form of fat. The energy stored as fat can be mobilized during periods of energy deprivation (hunger, fasting, diseases. The adipose tissue has also a homeostatic role regulating energy balance and functioning as endocrine organ that secretes substances that control body homeostasis. Two adipose tissues have been identified: white and brown adipose tissues (WAT and BAT with different phenotype, function and regulation. WAT stores energy, while BAT dissipates energy as heat. Brown and white adipocytes have different ontogenetic origin and lineage and specific markers of WAT and BAT have been identified. Brite or beige adipose tissue has been identified in WAT with some properties of BAT. Thyroid hormones exert pleiotropic actions, regulating the differentiation process in many tissues including the adipose tissue. Adipogenesis gives raise to mature adipocytes and is regulated by several transcription factors (c/EBPs, PPARs that coordinately activate specific genes, resulting in the adipocyte phenotype. T3 regulates several genes involved in lipid mobilization and storage and in thermogenesis. Both WAT and BAT are targets of thyroid hormones, which regulate genes crucial for their proper function: lipogenesis, lipolysis, thermogenesis, mitochondrial function, transcription factors, the availability of nutrients. T3 acts directly through specific TREs in the gene promoters, regulating transcription factors. The deiodinases D3, D2 and D1 regulate the availability of T3. D3 is activated during proliferation, while D2 is linked to the adipocyte differentiation program, providing T3 needed for lipogenesis and thermogenesis. We examine the differences between BAT, WAT and brite/beige adipocytes and the process that activate UCP1 in WAT and

  7. Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes

    Kern, P.A.; Marshall, S.; Eckel, R.H.

    1985-01-01

    To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific /sup 125/I-insulin binding. In addition, chloroquine induced an increase in cell-associated /sup 125/I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in medium containing 10% fetal bovine serum, there was a marked stimulation of CM and HR. The secretory response to serum (CM) correlated strongly with HR 24 h after preparation. In addition, HR was found to correlate logarithmically and inversely with body mass index. Insulin, at 400 ng/ml only, increased HR by 36 +/- 10%, an effect simulated by lower concentrations of insulin-like growth factor-1 (IGF1). Thus, LPL is produced and regulated in isolated human adipocytes. The degree of adiposity and serum are important regulators of HR activity, whereas insulin is stimulatory only at a pharmacologic concentration. This effect of insulin may be mediated through the IGF1 receptor. Isolated human adipocytes represent a novel and useful system for the study of LPL and lipid metabolism as well as for other aspects of adipocyte biology.

  8. Regulation of lipoprotein lipase in primary cultures of isolated human adipocytes

    To study the regulation of adipose tissue lipoprotein lipase (LPL) in human adipocytes, omental adipose tissue was obtained from healthy subjects and digested in collagenase. The isolated adipocytes thus obtained were suspended in Medium 199 and cultured at 37 degrees C. Cell viability was demonstrated in adipocytes cultured for up to 72 h by constancy of cell number, cell size, trypan-blue exclusion, and specific 125I-insulin binding. In addition, chloroquine induced an increase in cell-associated 125I-insulin at 24, 48, and 72 h after preparation. Thus, isolated adipocytes retained their ability to bind, internalize, and degrade insulin. LPL was measured as activity secreted into the culture medium (CM), released from cells by heparin (HR), and extracted from cell digests. A broad range of heparin concentrations produced a prompt release of LPL from a rapidly replenishable pool of cellular activity. When cells were cultured in medium containing 10% fetal bovine serum, there was a marked stimulation of CM and HR. The secretory response to serum (CM) correlated strongly with HR 24 h after preparation. In addition, HR was found to correlate logarithmically and inversely with body mass index. Insulin, at 400 ng/ml only, increased HR by 36 +/- 10%, an effect simulated by lower concentrations of insulin-like growth factor-1 (IGF1). Thus, LPL is produced and regulated in isolated human adipocytes. The degree of adiposity and serum are important regulators of HR activity, whereas insulin is stimulatory only at a pharmacologic concentration. This effect of insulin may be mediated through the IGF1 receptor. Isolated human adipocytes represent a novel and useful system for the study of LPL and lipid metabolism as well as for other aspects of adipocyte biology

  9. Lipase - Catalyzed glycerolysis of sunflower oil to produce partial glycerides.

    Zaher, F. A.

    1998-12-01

    Full Text Available Partial glycerides were prepared by glycerolysis of sunflower oil in presence of lipase enzyme as catalyst. Six lipases of different origins were used and compared for their catalytic activity. These include Chromobacterium lipase, pancreatic lipase, Rhizopus arrhizus lipase, lyophilized lipase (plant lipase in addition to two lipase preparations derived from Rhizopus japonicas; Lilipase A-10 and Lilipase B-2. Chromobacterium lipase was found to be the most active as glycerolysis catalyst whereas lyophilized lipase; a plant preparation from wheat germ was the least active. The results have also shown that the lipase type affects also the product polarity and hence its field of application as a food emulsifier. Less polar products can be obtained using Chromobacterium lipase whereas the more polar ones using a fungal lipase preparation «Lipase A-10». The product polarity is also influenced by the process temperature but the mode of its effect is different for different lipases.

    Se prepararon glicéridos parciales mediante glicerolisis de aceite de girasol en presencia de lipasa como catalizador. Seis lipasas de orígenes diferentes se utilizaron y compararon en función de su actividad catalítica. Estas incluyeron lipasa de Chromobacterium, lipasa pancreática, lipasa de Rhizopus arrhizus, lipasa liofilizada (lipasa vegetal además de dos preparaciones de lipasa derivadas de Rhizopus japonicus: lilipase A-10 y lilipase B-2. Se encontró que la lipasa de Chromobacterium fue la más activa como catalizador en la glicerolisis mientras que la lipasa liofilizada, preparación vegetal a partir de germen de trigo, fue la menos activa. Los resultados mostraron que los tipos de lipasa afectan también a la polaridad de los productos y por tanto a los rendimientos en su aplicación como emulsificantes alimentarios. Los productos menos polares pueden obtenerse usando lipasa de

  10. New lipase assay using Pomegranate oil coating in microtiter plates.

    Ülker, Serdar; Placidi, Camille; Point, Vanessa; Gadenne, Benoît; Serveau-Avesque, Carole; Canaan, Stéphane; Carrière, Frédéric; Cavalier, Jean-François

    2016-01-01

    Lipases play various roles in fat digestion, lipoprotein metabolism, and in the mobilization of fat stored in lipid bodies in animals, plants and microorganisms. In association with these physiological functions, there is an important field of research for discovering lipase inhibitors and developing new treatments of diseases such as obesity, atherosclerosis, diabetes and tuberculosis. In this context, the development of convenient, specific and sensitive analytical methods for the detection and assay of lipases and/or lipase inhibitors is of major importance. It is shown here that purified triacylglycerols (TAGs) from Punica granatum (Pomegranate) seed oil coated on microtiter plates can be used for the continuous assay of lipase activity by recording the variations with time of the UV absorption spectra at 275 nm. UV absorption is due the release of punicic acid (9Z,11E,13Z-octadeca-9,11,13-trienoic acid), a conjugated triene contained in Pomegranate oil. This new microtiter plate assay allows to accurately measure the activity of a wider range of lipases compared to the similar assay previously developed with Tung oil containing α-eleostearic acid (9Z,11E,13E-octadeca-9,11,13-trienoic acid), including the LipY lipase from Mycobacterium tuberculosis. Although punicic acid is a diastereoisomer of α-eleostearic acid, the Δ(13)cis double bound found in punicic acid gives a different structure to the acyl chain that probably favours the interaction of Pomegranate TAGs with the lipase active site. The microplate lipase assay using Pomegranate TAGs shows high sensitivity, reproducibility and remarkable relevance for the high-speed screening of lipases and/or lipase inhibitors directly from raw culture media without any purification step. PMID:26343557

  11. Butyl acetate synthesis using immobilized lipase in calcium alginate beads

    The esterification reaction of acetic acid and n-butanol using immobilized lipase encapsulated in calcium alginate beads (Lipase - CAB) and in chitosan coated calcium alginate beads (Lipase-CCAB) in n-hexane under mild reaction conditions were studied. Effects of temperature and substrate concentration (acetic acid and n-butanol) using Lipase - CAB, Lipase - CCAB and free lipase on the esterification reaction and their thermal stability towards esterification reaction were investigated. Results of temperature studies showed that the butyl acetate conversion increased with increase of temperature and reached the highest yield of about 70% around 50 degree Celsius for both immobilized systems but the yield of product catalyzed by free enzyme decreased as temperature was increased. Thermal stabilities studies showed that the Lipase-CCAB and Lipase-CAB were stable throughout the temperature range of 30-60 degree Celsius. However, free lipase became less stable at temperatures higher than 50 degree Celsius. The substrates, n-butanol and acetic acid exerted different effects on the esterification reaction and the reaction was favoured by higher acetic acid concentration than butanol. Kinetics parameters, Km and Vmax values for both substrates and the specific activities of the three enzyme system were also determined. The beads morphology was examined using SEM. Batch-wise operational stability studies for both immobilized systems demonstrated that the immobilized lipase performed better in the batch wise reactor system than the continuous bioreactor system and that the immobilized lipase remained active for at least 5 cycles of batch wise esterification reactions. (author)

  12. Direct effects of leptin on brown and white adipose tissue.

    Siegrist-Kaiser, C A; Pauli, V; Juge-Aubry, C E; Boss, O; Pernin, A; Chin, W W; Cusin, I; Rohner-Jeanrenaud, F; Burger, A G; Zapf, J; Meier, C A

    1997-01-01

    Leptin is thought to exert its actions on energy homeostasis through the long form of the leptin receptor (OB-Rb), which is present in the hypothalamus and in certain peripheral organs, including adipose tissue. In this study, we examined whether leptin has direct effects on the function of brown and white adipose tissue (BAT and WAT, respectively) at the metabolic and molecular levels. The chronic peripheral intravenous administration of leptin in vivo for 4 d resulted in a 1.6-fold increase in the in vivo glucose utilization index of BAT, whereas no significant change was found after intracerebroventricular administration compared with pair-fed control rats, compatible with a direct effect of leptin on BAT. The effect of leptin on WAT fat pads from lean Zucker Fa/ fa rats was assessed ex vivo, where a 9- and 16-fold increase in the rate of lipolysis was observed after 2 h of exposure to 0.1 and 10 nM leptin, respectively. In contrast, no increase in lipolysis was observed in the fat pads from obese fa/fa rats, which harbor an inactivating mutation in the OB-Rb. At the level of gene expression, leptin treatment for 24 h increased malic enzyme and lipoprotein lipase RNA 1.8+/-0.17 and 1.9+/-0.14-fold, respectively, while aP2 mRNA levels were unaltered in primary cultures of brown adipocytes from lean Fa/fa rats. Importantly, however, no significant effect of leptin was observed on these genes in brown adipocytes from obese fa/fa animals. The presence of OB-Rb receptors in adipose tissue was substantiated by the detection of its transcripts by RT-PCR, and leptin treatment in vivo and in vitro activated the specific STATs implicated in the signaling pathway of the OB-Rb. Taken together, our data strongly suggest that leptin has direct effects on BAT and WAT, resulting in the activation of the Jak/STAT pathway and the increased expression of certain target genes, which may partially account for the observed increase in glucose utilization and lipolysis in leptin

  13. Combining decellularized human adipose tissue extracellular matrix and adipose-derived stem cells for adipose tissue engineering

    Wang, Lina; Johnson, Joshua A.; Zhang, Qixu; Elisabeth K. Beahm

    2013-01-01

    Repair of soft-tissue defects resulting from lumpectomy or mastectomy has become an important rehabilitation process for breast cancer patients. This study aimed to provide an adipose tissue engineering platform for soft-tissue defect repair by combining decellularized human adipose tissue extracellular matrix (hDAM) and human adipose-derived stem cells (hASCs). To derive hDAM, incised human adipose tissues underwent a decellularization process. Effective cell removal and lipid removal were p...

  14. Resistance to diet-induced adiposity in cannabinoid receptor-1 deficient mice is not due to impaired adipocyte function

    Oosterveer Maaike H

    2011-12-01

    Full Text Available Abstract Background Overactivity and/or dysregulation of the endocannabinoid system (ECS contribute to development of obesity. In vitro studies indicate a regulatory role for the cannabinoid receptor 1 (CB1 in adipocyte function and CB1-receptor deficient (CB1-/- mice are resistant to high fat diet-induced obesity. Whether this phenotype of CB1-/- mice is related to altered fat metabolism in adipose tissue is unknown. Methods We evaluated adipose tissue differentiation/proliferation markers and quantified lipogenic and lipolytic activities in fat tissues of CB1-/- and CB1+/+ mice fed a high-fat (HF or a high-fat/fish oil (HF/FO diet as compared to animals receiving a low-fat chow diet. Comparison between HF diet and HF/FO diet allowed to investigate the influence of dietary fat quality on adipose tissue biology in relation to CB1 functioning. Results The adiposity-resistant phenotype of the CB1-/- mice was characterized by reduced fat mass and adipocyte size in HF and HF/FO-fed CB1-/- mice in parallel to a significant increase in energy expenditure as compared to CB1+/+ mice. The expression levels of adipocyte differentiation and proliferation markers were however maintained in these animals. Consistent with unaltered lipogenic gene expression, the fatty acid synthesis rates in adipose tissues from CB1-/- and CB1+/+ mice were unchanged. Whole-body and adipose-specific lipoprotein lipase (LPL activities were also not altered in CB1-/- mice. Conclusions These findings indicate that protection against diet-induced adiposity in CB1-deficient mice is not related to changes in adipocyte function per se, but rather results from increased energy dissipation by oxidative and non-oxidative pathways.

  15. Minireview: adiposity, inflammation, and atherogenesis.

    Lyon, Christopher J; Law, Ronald E; Hsueh, Willa A

    2003-06-01

    Adipose tissue is a dynamic endocrine organ that secretes a number of factors that are increasingly recognized to contribute to systemic and vascular inflammation. Several of these factors, collectively referred to as adipokines, have now been shown regulate, directly or indirectly, a number of the processes that contribute to the development of atherosclerosis, including hypertension, endothelial dysfunction, insulin resistance, and vascular remodeling. Several adipokines are preferentially expressed in visceral adipose tissue, and the secretion of proinflammatory adipokines is elevated with increasing adiposity. Not surprisingly, approaches that reduce adipose tissue depots, including surgical fat removal, exercise, and reduced caloric intake, improve proinflammatory adipokine levels and reduce the severity of their resultant pathologies. Systemic adipokine levels can also be favorably altered by treatment with several of the existing drug classes used to treat insulin resistance, hypertension, and hypercholesterolemia. Greater understanding of adipokine regulation, however, should result in the design of improved treatment strategies to control disease states associated with increase adiposity, an important outcome in view of the growing worldwide epidemic of obesity. PMID:12746274

  16. Engineering of vascularized adipose constructs.

    Wiggenhauser, Paul S; Müller, Daniel F; Melchels, Ferry P W; Egaña, José T; Storck, Katharina; Mayer, Helena; Leuthner, Peter; Skodacek, Daniel; Hopfner, Ursula; Machens, Hans G; Staudenmaier, Rainer; Schantz, Jan T

    2012-03-01

    Adipose tissue engineering offers a promising alternative to the current surgical techniques for the treatment of soft tissue defects. It is a challenge to find the appropriate scaffold that not only represents a suitable environment for cells but also allows fabrication of customized tissue constructs, particularly in breast surgery. We investigated two different scaffolds for their potential use in adipose tissue regeneration. Sponge-like polyurethane scaffolds were prepared by mold casting with methylal as foaming agent, whereas polycaprolactone scaffolds with highly regular stacked-fiber architecture were fabricated with fused deposition modeling. Both scaffold types were seeded with human adipose tissue-derived precursor cells, cultured and implanted in nude mice using a femoral arteriovenous flow-through vessel loop for angiogenesis. In vitro, cells attached to both scaffolds and differentiated into adipocytes. In vivo, angiogenesis and adipose tissue formation were observed throughout both constructs after 2 and 4 weeks, with angiogenesis being comparable in seeded and unseeded constructs. Fibrous tissue formation and adipogenesis were more pronounced on polyurethane foam scaffolds than on polycaprolactone prototyped scaffolds. In conclusion, both scaffold designs can be effectively used for adipose tissue engineering. PMID:21850493

  17. Effect of prepartal ad libitum feeding of grass silage on transcriptional adaptations of the liver and subcutaneous adipose tissue in dairy cows during the periparturient period.

    Selim, S; Kokkonen, T; Taponen, J; Vanhatalo, A; Elo, K

    2015-08-01

    Prepartal energy overfeeding may predispose cows to a state of increased insulin resistance with greater lipolysis after parturition. The aim of the study was to evaluate the effects of prepartal overfeeding in terms of abundant grass silage ration on the liver and subcutaneous adipose tissue (SAT) gene expression around parturition. Sixteen multiparous Finnish Ayrshire dairy cows were fed ad libitum either grass silage [high energy, HE; 144 MJ/d of metabolizable energy (ME) intake, n=8] or a mixture of grass silage, wheat straw, and rapeseed meal [55:40:5 (CON), 109 MJ/d of ME, n=8] during the dry period (58.2±4.89 d, mean ± standard deviation). Tissue biopsies and blood samples were collected at -14 (±4.98), 1, and 7 d relative to the actual parturition date. The HE cows had greater total dry matter intake, ME intake, and ME balance during the dry period than the CON cows. Compared with CON, the increases in body weight and body condition score were greater in HE during the dry period. Milk yield during the first 2 wk of lactation was not different between the groups. Plasma glucose, nonesterified fatty acids, insulin, glucagon, and β-hydroxybutyrate did not differ between the groups during the transition period. Dietary treatment did not affect hepatic triglyceride content; however, a delayed increase in hepatic total lipid content was observed in the HE cows at d 1 postpartum. Hepatic cytosolic phosphoenolpyruvate carboxykinase 1 mRNA expression was lower in HE than in CON at d 1 and 7 postpartum. Adiponectin receptor 1 and 2 mRNA abundance tended to be lower in SAT of HE than CON. Lower lipoprotein lipase, leptin, and stearoyl-coenzyme A desaturase mRNA abundances were observed at d 7 postpartum in SAT of the HE cows compared with the CON cows. We concluded that prepartal ad libitum feeding of grass silage may decrease insulin sensitivity and lipogenesis in SAT during peripartal period and may attenuate the increase of hepatic gluconeogenic capacity from

  18. Lipolysis in human adipose tissue during exercise

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

    2002-01-01

    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 and...

  19. Clofibrate causes an upregulation of PPAR-{alpha} target genes but does not alter expression of SREBP target genes in liver and adipose tissue of pigs.

    Luci, Sebastian; Giemsa, Beatrice; Kluge, Holger; Eder, Klaus

    2007-07-01

    This study investigated the effect of clofibrate treatment on expression of target genes of peroxisome proliferator-activated receptor (PPAR)-alpha and various genes of the lipid metabolism in liver and adipose tissue of pigs. An experiment with 18 pigs was performed in which pigs were fed either a control diet or the same diet supplemented with 5 g clofibrate/kg for 28 days. Pigs treated with clofibrate had heavier livers, moderately increased mRNA concentrations of various PPAR-alpha target genes in liver and adipose tissue, a higher concentration of 3-hydroxybutyrate, and markedly lower concentrations of triglycerides and cholesterol in plasma and lipoproteins than control pigs (P liver and adipose tissue and mRNA concentrations of apolipoproteins A-I, A-II, and C-III in the liver were not different between both groups of pigs. In conclusion, this study shows that clofibrate treatment activates PPAR-alpha in liver and adipose tissue and has a strong hypotriglyceridemic and hypocholesterolemic effect in pigs. The finding that mRNA concentrations of some proteins responsible for the hypolipidemic action of fibrates in humans were not altered suggests that there were certain differences in the mode of action compared with humans. It is also shown that PPAR-alpha activation by clofibrate does not affect hepatic expression of SREBP target genes involved in synthesis of triglycerides and cholesterol homeostasis in liver and adipose tissue of pigs. PMID:17363680

  20. Adipocyte hypertrophy, inflammation and fibrosis characterize subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes.

    A M Josefin Henninger

    Full Text Available BACKGROUND: The adipose tissue is important for development of insulin resistance and type 2 diabetes and adipose tissue dysfunction has been proposed as an underlying cause. In the present study we investigated presence of adipocyte hypertrophy, and gene expression pattern of adipose tissue dysfunction in the subcutaneous adipose tissue of healthy, non-obese subjects predisposed to type 2 diabetes compared to matched control subjects with no known genetic predisposition for type 2 diabetes. METHOD: Seventeen healthy and non-obese subjects with known genetic predisposition for type 2 diabetes (first-degree relatives, FDRs and 17 control subjects were recruited. The groups were matched for gender and BMI and had similar age. Glucose tolerance was determined by an oral glucose tolerance test and insulin sensitivity was calculated using HOMA-index. Blood samples were collected and subcutaneous abdominal adipose tissue biopsies obtained for gene expression analysis and adipocyte cell size measurement. RESULTS: Our findings show that, in spite of similar age, BMI and percent body fat, FDRs displayed adipocyte hypertrophy, as well as higher waist/hip ratio, fasting insulin levels, HOMA-IR and serum triglycerides. Adipocyte hypertrophy in the FDR group, but not among controls, was associated with measures of impaired insulin sensitivity. The adipocyte hypertrophy was accompanied by increased inflammation and Wnt-signal activation. In addition, signs of tissue remodeling and fibrosis were observed indicating presence of early alterations associated with adipose tissue dysfunction in the FDRs. CONCLUSION: Genetic predisposition for type 2 diabetes is associated with impaired insulin sensitivity, adipocyte hypertrophy and other markers of adipose tissue dysfunction. A dysregulated subcutaneous adipose tissue may be a major susceptibility factor for later development of type 2 diabetes.

  1. Role of Triglyceride-rich Lipoproteins in Renal Injury

    Ng, Kit Fai; AUNG, HNIN HNIN; Rutledge, John C.

    2011-01-01

    Dyslipidemia is implicated as a risk factor for the development of atherosclerosis. Specifically triglyceride-rich lipoproteins (TGRL) and their lipolysis products are shown to be pro-inflammatory and pro-apoptosis in both in vivo and in vitro studies with endothelium. However the role of TGRL in the progression of kidney diseases is not clear. Epidemiology studies demonstrated a correlation between renal disease and blood lipids. Recent evidence suggests that the mechanism may involve cellul...

  2. Surfactant-activated lipase hybrid nanoflowers with enhanced enzymatic performance

    Cui, Jiandong; Zhao, Yamin; Liu, Ronglin; Zhong, Cheng; Jia, Shiru

    2016-01-01

    Increasing numbers of materials have been extensively used as platforms for enzyme immobilization to improve catalytic performance. However, activity of the most of the enzymes was declined after immobilization. Here, we develop a surfactant-activated lipase-inorganic flowerlike hybrid nanomaterials with rational design based on interfacial activation and self-assembly. The resulting surfactant-activated lipase-inorganic hybird nanoflower (activated hNF-lipase) exhibited 460% and 200% higher activity than native lipase and conventional lipase-inorganic hybird nanoflower (hNF-lipase). Furthermore, the activated hNF-lipase displayed good reusability due to its monodispersity and mechanical properties, and had excellent long-time stability. The superior catalytic performances were attributed to both the conformational modulation of surfactants and hierarchical structure of nanoflowers, which not only anchored lipases in an active form, but also decreased the enzyme-support negative interaction and mass-transfer limitations. This new biocatalytic system is promising to find widespread use in applications related to biomedicine, biosensor, and biodiesel. PMID:27297609

  3. Vibrational and structural investigations on adipose tissues

    Giarola, Marco; Guella, G.; Mariotto, G.; Monti, Francesca; Rossi, Barbara; Sanson, Andrea; Sbarbati, Andrea

    2008-01-01

    Abstract Two types of adipose tissue are found in mammals, including humans: the white adipose tissue (WAT) and the brown adipose tissue (BAT). The WAT has a major role in lipid storage and body thermal insulation, while the BAT is a thermogenic tissue that produces heat by oxidizing fatty acids. Both structural characterization and spectroscopic discrimination of these different adipose tissues are matter of current interest, also in view of possible medical and ...

  4. Adiposity, type 2 diabetes and Alzheimer's disease

    Luchsinger, José A.; Gustafson, Deborah R

    2009-01-01

    This manuscript provides a comprehensive review of the epidemiologic evidence linking the continuum of adiposity and type 2 diabetes (T2D) with Alzheimer's disease (AD). The mechanisms relating adiposity and T2D to AD may include hyperinsulinemia, advanced products of glycosilation, cerebrovascular disease, and products of adipose tissue metabolism. Elevated adiposity in middle age is related to a higher risk of AD but the data on this association in old age is conflicting. Several studies ha...

  5. Relationship of glycemic and triglycerides with BMI in diabetic patients

    Background: Diabetes mellitus (DM) is a metabolic disorder characterised by chronic hyperglycaemia with disturbances in carbohydrate, fat and protein metabolism arising from defect in insulin secretion or action or both. The clinical guidelines recommend measurement of BMI as vital signs for evaluating the obese and diabetic patients. Methods: This study was carried out on 160 diabetics, which were divided on the basis of BMI into obese (120) and non-obese (40) diabetics from Peshawar district. All patients had their triglycerides and glucose checked after over night fast. Results: The serum triglyceride in diabetics having BMI >30 (obese) was increased as compared to patients having BMI <30 (non-obese). The comparison of serum glucose level in obese diabetics was found to be significantly raised as compared to non-obese diabetics. Conclusions and Recommendations: It was concluded that dyslipidemia is common in all diabetics. The abnormal triglyceride level can improve with good glycemic control, but do not reach the normal state. Good glycaemic control, Reducing BMI, periodic checkups of lipids and blood glucose are recommended for all diabetics in order to avoid complications. (author)

  6. Skeletal muscle apolipoprotein B expression reduces muscular triglyceride accumulation

    Bartels, Emil D; Ploug, Thorkil; Størling, Joachim;

    2014-01-01

    Abstract Background. Lipid accumulation in skeletal muscle is associated with impaired insulin sensitivity in type 2 diabetes. In cardiac myocytes, lipoprotein secretion controlled by apolipoproteinB (apoB) and microsomal triglyceride transfer protein (MTP) affects lipid homeostasis. Design....... In this study, we investigated whether expression of a human apoB transgene affects triglyceride accumulation and insulin sensitivity in skeletal muscle in fat fed obese mice. Results. Expression of apoB and MTP mRNA and the human apoB transgene was seen in skeletal muscle of the transgene mice. Human apo......B transgenic mice accumulated 28% less triglycerides in skeletal myocytes after one year of fat-feeding as compared with WT mice (32 ± 5, n = 10 vs. 44 ± 4 nmol/mg ww, n = 13, p = 0.04). Moreover, expression of human apoB in fat-fed mice was associated with 32% (p = 0.02) and 37% (p = 0.01) lower plasma...

  7. Lowering triglycerides to modify cardiovascular risk: will icosapent deliver?

    Scherer DJ

    2015-03-01

    Full Text Available Daniel J Scherer,1 Stephen J Nicholls2 1Cardiovascular Investigation Unit, Royal Adelaide Hospital, 2South Australian Health and Medical Research Institute, University of Adelaide, Adelaide, SA, Australia Abstract: Despite the clinical benefits of lowering levels of low-density lipoprotein cholesterol, many patients continue to experience cardiovascular events. This residual risk suggests that additional risk factors require aggressive modification to result in more effective prevention of cardiovascular disease. Hypertriglyceridemia has presented a considerable challenge with regard to understanding its role in the promotion of cardiovascular risk. Increasing evidence has established a clear causal role for elevated triglyceride levels in vascular risk. As a result, there is increasing interest in the development of specific therapeutic strategies that directly target hypertriglyceridemia. This has seen a resurgence in the use of omega-3 fatty acids for the therapeutic lowering of triglyceride levels. The role of these agents and other emerging strategies to reduce triglyceride levels in order to decrease vascular risk are reviewed. Keywords: hypertriglyceridemia, omega-3 fatty acid, fish oil, cardiovascular risk, lipids

  8. Triglyceride-mediated pathways and coronary disease: collaborative analysis of 101 studies

    Sarwar, Nadeem; Sandhu, Manjinder S; Ricketts, Sally L;

    2010-01-01

    Whether triglyceride-mediated pathways are causally relevant to coronary heart disease is uncertain. We studied a genetic variant that regulates triglyceride concentration to help judge likelihood of causality....

  9. Tenomodulin promotes human adipocyte differentiation and beneficial visceral adipose tissue expansion

    Senol-Cosar, Ozlem; Flach, Rachel J. Roth; DiStefano, Marina; Chawla, Anil; Nicoloro, Sarah; Straubhaar, Juerg; Hardy, Olga T.; Noh, Hye Lim; Kim, Jason K.; Wabitsch, Martin; Scherer, Philipp E.; Czech, Michael P.

    2016-01-01

    Proper regulation of energy storage in adipose tissue is crucial for maintaining insulin sensitivity and molecules contributing to this process have not been fully revealed. Here we show that type II transmembrane protein tenomodulin (TNMD) is upregulated in adipose tissue of insulin-resistant versus insulin-sensitive individuals, who were matched for body mass index (BMI). TNMD expression increases in human preadipocytes during differentiation, whereas silencing TNMD blocks adipogenesis. Upon high-fat diet feeding, transgenic mice overexpressing Tnmd develop increased epididymal white adipose tissue (eWAT) mass, and preadipocytes derived from Tnmd transgenic mice display greater proliferation, consistent with elevated adipogenesis. In Tnmd transgenic mice, lipogenic genes are upregulated in eWAT, as is Ucp1 in brown fat, while liver triglyceride accumulation is attenuated. Despite expanded eWAT, transgenic animals display improved systemic insulin sensitivity, decreased collagen deposition and inflammation in eWAT, and increased insulin stimulation of Akt phosphorylation. Our data suggest that TNMD acts as a protective factor in visceral adipose tissue to alleviate insulin resistance in obesity. PMID:26880110

  10. Activation of mTORC1 is essential for β-adrenergic stimulation of adipose browning.

    Liu, Dianxin; Bordicchia, Marica; Zhang, Chaoying; Fang, Huafeng; Wei, Wan; Li, Jian-Liang; Guilherme, Adilson; Guntur, Kalyani; Czech, Michael P; Collins, Sheila

    2016-05-01

    A classic metabolic concept posits that insulin promotes energy storage and adipose expansion, while catecholamines stimulate release of adipose energy stores by hydrolysis of triglycerides through β-adrenergic receptor (βARs) and protein kinase A (PKA) signaling. Here, we have shown that a key hub in the insulin signaling pathway, activation of p70 ribosomal S6 kinase (S6K1) through mTORC1, is also triggered by PKA activation in both mouse and human adipocytes. Mice with mTORC1 impairment, either through adipocyte-specific deletion of Raptor or pharmacologic rapamycin treatment, were refractory to the well-known βAR-dependent increase of uncoupling protein UCP1 expression and expansion of beige/brite adipocytes (so-called browning) in white adipose tissue (WAT). Mechanistically, PKA directly phosphorylated mTOR and RAPTOR on unique serine residues, an effect that was independent of insulin/AKT signaling. Abrogation of the PKA site within RAPTOR disrupted βAR/mTORC1 activation of S6K1 without affecting mTORC1 activation by insulin. Conversely, a phosphomimetic RAPTOR augmented S6K1 activity. Together, these studies reveal a signaling pathway from βARs and PKA through mTORC1 that is required for adipose browning by catecholamines and provides potential therapeutic strategies to enhance energy expenditure and combat metabolic disease. PMID:27018708

  11. Radioisotopic method for the measurement of lipolysis in small samples of human adipose tissue

    To facilitate the study of adrenoreceptor response in small needle biopsy samples of human subcutaneous adipose tissue, we developed a dual radioisotopic technique for measuring lipolysis rate. Aliquots (20-75 mg) of adipose tissue fragments were incubated in a buffered albumin medium containing [3H]palmitate and [14C]glucose, each of high specific activity. In neutral glycerides synthesized in this system, [14C]glucose is incorporated exclusively into the glyceride-glycerol moiety and 3H appears solely in the esterified fatty acid. Alpha-2 and beta-1 adrenoreceptor activation of tissue incubated in this system does not alter rates of 14C-labeled glyceride accumulation, but does produce a respective increase or decrease in the specific activity of fatty acids esterified into newly synthesized glycerides. This alteration in esterified fatty acid specific activity is reflected in the ratio of 14C:3H in newly synthesized triglycerides extracted from the incubated adipose tissue. There is a high correlation (r . 0.90) between the 14C:3H ratio in triglycerides and the rate of lipolysis as reflected in glycerol release into the incubation medium. The degree of adrenoreceptor activation by various concentrations of lipolytic and anti-lipolytic substances can be assessed by comparing this ratio in stimulated tissue to that characterizing unstimulated tissue or the incubation medium. This technique permits the study of very small, unweighed tissue biopsy fragments, the only limitation on sensitivity being the specific activity of the medium glucose and palmitate. It is, therefore, useful for serial examinations of adipose tissue adrenoreceptor dose-response characteristics under a variety of clinical circumstances

  12. Lipase-catalyzed synthesis of ascorbyl oleate in acetone: optimization of reaction conditions and lipase reusability.

    Stojanović, Marija; Velićković, Dušan; Dimitrijević, Aleksandra; Milosavić, Nenad; Knežević-Jugović, Zorica; Bezbradica, Dejan

    2013-01-01

    Lipase-catalyzed ascorbyl oleate synthesis is eco-friendly and selective way of production of liposoluble biocompatible antioxidants, but still not present on an industrial level due to the high biocatalyst costs. In this study, response surface methodology was applied in order to estimate influence of individual experimental factors, identify interactions among them, and to determine optimum conditions for enzymatic synthesis of ascorbyl oleate in acetone, in terms of limiting substrate conversion, product yield, and yield per mass of consumed enzyme. As a biocatalyst, commercial immobilized preparation of lipase B from Candida antarctica, Novozym 435, was used. In order to develop cost-effective process, at reaction conditions at which maximum amount of product per mass of biocatalyst was produced (60°C, 0.018 % (v/v) of water, 0.135 M of vitamin C, substrates molar ratio 1:8, and 0.2 % (w/v) of lipase), possibilities for further increase of ester yield were investigated. Addition of molecular sieves at 4(th) hour of reaction enabled increase of yield from 16.7 mmol g⁻¹ to 19.3 mmol g⁻¹. Operational stability study revealed that after ten reaction cycles enzyme retained 48 % of its initial activity. Optimized synthesis with well-timed molecular sieves addition and repeated use of lipase provided production of 153 mmol per gram of enzyme. Further improvement of productivity was achieved using procedure for the enzyme reactivation. PMID:23985489

  13. Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues

    Chen, Yu-Jen; Liu, Hui-Yu; Chang, Yun-Tsui; Cheng, Ying-Hung; Harry J. Mersmann; Kuo, Wen-Hung; Ding, Shih-Torng

    2016-01-01

    Obesity is an unconstrained worldwide epidemic. Unraveling molecular controls in adipose tissue development holds promise to treat obesity or diabetes. Although numerous immortalized adipogenic cell lines have been established, adipose-derived stem cells from the stromal vascular fraction of subcutaneous white adipose tissues provide a reliable cellular system ex vivo much closer to adipose development in vivo. Pig adipose-derived stem cells (pADSC) are isolated from 7- to 9-day old piglets. ...

  14. Beneficial effects of adding lipase enzyme to broiler diet

    A total number of 300 Ross broiler chicks were obtained from commercial hatchery at one day of age. The chicks were divided into three groups (50 males and 50 females in each). The first and second groups were supplemented with 3000 and 2000 lU/kg diet of lipase enzyme, respectively, while the third group served as control and fed on basal diet. Birds fed on diets that supplemented with lipase enzyme showed significant increase in body weight and dry matter intake, as well as fats and protein content dry matters. The serum lipase activity showed significant increase in treated groups compared to the control. Non-significant changes were determined in serum total lipids, T3, T4 and ash content. Birds supplemented with lipase showed significant decrease in cholesterol concentration. It could be concluded that birds fed diets containing 2000 or 3000 lU/kg diet of lipase enzyme exhibited improvement in broiler performance

  15. Characteristic properties of lipase from cowpea (vigna unguiculata) seedlings

    Lipase activity was assayed in 4 days old cowpea seedlings using olive oil emulsion stabilized with 10% gum acacia as a substrate. The maximum lipase activity was observed at pH 8.0 with Tris-HCI buffer and at 30 degree C. The pH stability was found in between 7.5-8.5. Lipase activity was fairly stable up to 60 degree C and retaining 80% activity whereas, 26% lipase activity was remaining at 100 degree C within 15 minutes. Lipase activity was slightly increased in the presence of MnC/sub 2/ and decreased by the addition of Triton X 100, Tween 80, ZnCI/sub 2/ and mercaptoethanol. (author)

  16. Raman Spectroscopic Analysis of Biochemical Changes in Individual Triglyceride-Rich Lipoproteins in the Pre- and Postprandial State

    Chan, J; Motton, D; Rutledge, J; Keim, N; Huser, T

    2004-09-13

    Individual triglyceride-rich lipoprotein (TGRL) particles derived from human volunteers are non-destructively analyzed by laser tweezers Raman microspectroscopy and information on their composition and distribution is obtained. The Raman signature of single optically trapped very low-density lipoproteins (VLDL), a subclass of TGRL, which play an important role in cardiovascular disease, exhibits distinct peaks associated with molecular vibrations of fatty acids, proteins, lipids, and structural rearrangements of lipids. Our analysis of pre- and postprandial VLDL exhibits the signature of biochemical changes in individual lipoprotein particles following the consumption of meals. Interaction of VLDL with endothelium leads to the breakdown of complex triacylglycerols and the formation of a highly ordered core of free saturated fatty acids in the particle. A particle distribution analysis reveals trends in the degree to which this process has occurred in particles at different times during the postprandial period. Differences in particle distributions based on the different ratios of polyunsaturated to saturated fats in the consumed meals are also easily discerned. Individual lipoprotein particles hydrolyzed in-vitro through addition of lipoprotein lipase (LpL) exhibit strikingly similar changes in their Raman spectra. These results demonstrate the feasibility of monitoring the dynamics of lipid metabolism of individual TGRL particles as they interact with LpL in the endothelial cell wall using Raman spectroscopy.

  17. Disulfide Bond in Pseudomonas aeruginosa Lipase Stabilizes the Structure but Is Not Required for Interaction with Its Foldase

    Liebeton, Klaus; Zacharias, Annette; Jaeger, Karl-Erich

    2001-01-01

    Pseudomonas aeruginosa secretes a 29-kDa lipase which is dependent for folding on the presence of the lipase-specific foldase Lif. The lipase contains two cysteine residues which form an intramolecular disulfide bond. Variant lipases with either one or both cysteines replaced by serines showed severely reduced levels of extracellular lipase activity, indicating the importance of the disulfide bond for secretion of lipase through the outer membrane. Wild-type and variant lipase genes fused to ...

  18. Profile Triglycerides Japanese Quail (Coturnix coturnix japonica) After Giving Turmeric (Curcuma longa) Powder

    Sukarman Hadi jaya Putra; Tyas Rini Saraswati; Sri Isdadiyanto

    2015-01-01

    The purpose of this study was to determine the triglyceride profile of Japanese quail (Coturnix coturnix japonica) after being given the parameters of turmeric (Curcuma longa) powder; feed intake, profiles of liver triglycerides, profiles of serum triglycerides and profiles of meat triglycerides. This study uses an experimental method with A Completely Randomized Design Pattern. Test animals used were 45 female Japanese quails were divided into 3 groups, namely; P0: quail were not given turme...

  19. Adipose-Derived Stem Cells

    Toyserkani, Navid Mohamadpour; Quaade, Marlene Louise; Sheikh, Søren Paludan;

    2015-01-01

    Emerging evidence has shown that adipose tissue is the richest and most accessible source of mesenchymal stem cells. Many different therapies for chronic wounds exist with varying success rates. The capacity of adipose-derived stem cells (ASCs) to promote angiogenesis, secrete growth factors......, regulate the inflammatory process, and differentiate into multiple cell types makes them a potential ideal therapy for chronic wounds. The aim of this article was to review all preclinical trials using ASCs in problem wound models. A systematic search was performed and 12 studies were found where different...

  20. Enzymatic interesterification of palm stearin and coconut oil by a dual lipase system

    Ibrahim, Nuzul Amri Bin; Guo, Zheng; Xu, Xuebing

    2008-01-01

    Enzymatic interesterification of palm stearin with coconut oil was conducted by applying a dual lipase system in comparison with individual lipase-catalyzed reactions. The results indicated that a synergistic effect occurred for many lipase combinations, but largely depending on the lipase species...

  1. Mechanism of acetaldehyde-induced deactivation of microbial lipases

    Jaeger Karl E

    2011-02-01

    Full Text Available Abstract Background Microbial lipases represent the most important class of biocatalysts used for a wealth of applications in organic synthesis. An often applied reaction is the lipase-catalyzed transesterification of vinyl esters and alcohols resulting in the formation of acetaldehyde which is known to deactivate microbial lipases, presumably by structural changes caused by initial Schiff-base formation at solvent accessible lysine residues. Previous studies showed that several lipases were sensitive toward acetaldehyde deactivation whereas others were insensitive; however, a general explanation of the acetaldehyde-induced inactivation mechanism is missing. Results Based on five microbial lipases from Candida rugosa, Rhizopus oryzae, Pseudomonas fluorescens and Bacillus subtilis we demonstrate that the protonation state of lysine ε-amino groups is decisive for their sensitivity toward acetaldehyde. Analysis of the diverse modification products of Bacillus subtilis lipases in the presence of acetaldehyde revealed several stable products such as α,β-unsaturated polyenals, which result from base and/or amino acid catalyzed aldol condensation of acetaldehyde. Our studies indicate that these products induce the formation of stable Michael-adducts at solvent-accessible amino acids and thus lead to enzyme deactivation. Further, our results indicate Schiff-base formation with acetaldehyde to be involved in crosslinking of lipase molecules. Conclusions Differences in stability observed with various commercially available microbial lipases most probably result from different purification procedures carried out by the respective manufacturers. We observed that the pH of the buffer used prior to lyophilization of the enzyme sample is of utmost importance. The mechanism of acetaldehyde-induced deactivation of microbial lipases involves the generation of α,β-unsaturated polyenals from acetaldehyde which subsequently form stable Michael-adducts with the

  2. La lipase de Candida rugosa : caractérisation biochimique

    Mtibaa Hounaida

    2002-01-01

    Full Text Available Les lipases ou triacylglycérols hydrolases (EC 3.1.1.3 sont des enzymes qui agissent en milieu hétérogène. Ces enzymes catalysent l’hydrolyse des liaisons esters des triacylglycérols à l’interface huile/eau [1]. Leur particularité vient du fait que ces enzymes sont plus actives sur les lipides qui sont sous forme agrégée [2]. Les lipases sont présentes dans la plupart des tissus animaux et végétaux ainsi que chez les microorganismes qui constituent une source importante de production de lipases à grande échelle. À ce jour, de nombreuses lipases de microorganismes ont été purifiées et caractérisées et certaines d’entres elles ont été cristallisées (lipase de Pseudomonas glumae [3], lipase de Rhizomucor miehei [4], lipase Geotrichum candidum [5], lipase de Candida rugosa [6].... La lipase de Candida cylindracea (qui est l’ancien nom de Candida rugosa a été cristallisée en présence et en l’absence d’inhibiteurs [7]. Il s’agit d’une alpha/beta hydrolase comprenant 11 brins beta entourés par 8 hélices alpha [6]. La triade catalytique est cachée sous un flap constitué de 26 résidus d’aminoacides. Dans le présent travail, nous avons cherché à étudier quelques caractéristiques biochimiques de la lipase de Candida rugosa (CRL qui a été purifiée dans notre laboratoire à partir de la poudre commercialisée.

  3. Isolation of lipase producing thermophilic bacteria: optimization of production and reaction conditions for lipase from Geobacillus sp.

    Mehta, Akshita; Kumar, Rakesh; Gupta, Reena

    2012-12-01

    Lipases catalyze the hydrolysis and the synthesis of esters formed from glycerol and long chain fatty acids. Lipases occur widely in nature, but only microbial lipases are commercially significant. In the present study, thirty-two bacterial strains, isolated from soil sample of a hot spring were screened for lipase production. The strain TS-4, which gave maximum activity, was identified as Geobacillus sp. at MTCC, IMTECH, Chandigarh. The isolated lipase producing bacteria were grown on minimal salt medium containing olive oil. Maximal quantities of lipase were produced when 30 h old inoculum was used at 10% (v/v) in production medium and incubated in shaking conditions (150 rpm) for 72 h. The optimal temperature and pH for the bacterial growth and lipase production were found to be 60°C and 9.5, respectively. Maximal enzyme production resulted when mustard oil was used as carbon source and yeast extract as sole nitrogen source at a concentration of 1% (v/v) and 0.15% (w/v), respectively. The different optimized reaction parameters were temperature 65°C, pH 8.5, incubation time 10 min and substrate p-nitrophenyl palmitate. The Km and Vmax values of enzyme were found to be 14 mM and 17.86 μmol ml-1min-1, respectively, with p-nitrophenyl palmitate as substrate. All metal ions studied (1 mM) increased the lipase activity. PMID:23195552

  4. Relationship of adiposity to the population distribution of plasma triglyceride concentrations in vigorously active men and women

    Williams, Paul T.

    2002-01-01

    Context and Objective: Vigorous exercise, alcohol and weight loss are all known to increase HDL-cholesterol, however, it is not known whether these interventions raise low HDL as effectively as has been demonstrated for normal HDL. Design: Physican-supplied medical data from 7,288 male and 2,359 female runners were divided into five strata according to their self-reported usual running distance, reported alcohol intake, body mass index (BMI) or waist circumference. Within each stratum, ...

  5. Lipases as Tools in the Synthesis of Prodrugs from Racemic 9-(2,3-Dihydroxypropyladenine

    Marcela Krečmerová

    2012-11-01

    Full Text Available Lipases from Geotrichum candidum 4013 (extracellular lipase and cell-bound lipase were immobilized by adsorption on chitosan beads. The enzyme preparations were tested in the synthesis of ester prodrugs from racemic 9-(2,3-dihydroxypropyladenine in dimethylformamide with different vinyl esters (acetate, butyrate, decanoate, laurate, palmitate. The transesterification activities of these immobilized enzymes were compared with commercially available lipases (lipase from hog pancreas, Aspergillus niger, Candida antarctica, Pseudomonas fluorescens. Lipase from Candida antarctica was found to be the most efficient enzyme regarding chemical yield of the desired products, while transesterification by lipase from Aspergillus niger resulted in lower yields.

  6. Modeling of an immobilized lipase tubular reactor for the production of glycerol and fatty acids from oils

    Advances in the design of a bioreactor in the fats and oils industry have permitted the hydrolysis of triglycerides in mild conditions and improved productivity while avoiding the formation of unwanted byproducts. The present work develops a mathematical model that describes the hydrolytic activity of a tubular reactor with immobilized lipases for the production of glycerol and fatty acids from the oil trade. Runge Kuttas numerical method of high order has been applied, considering that there is no accumulation of the substratum in the surface of the membrane, where the enzyme is. At the same time, different equations based on the kinetic model of Michaelis Mentens and the Ping-Pong bi-bi mechanism were examined. Experimental data in discontinuous systems are the basis for the development of the quantitative mathematical model that was used to simulate the process computationally. The obtained results allow for optimizing both the operative variables and the economic aspects of industrial processes. (Author)

  7. Effects of Regioselectivity and Lipid Class Specificity of Lipases on Transesterification, Exemplified by Biodiesel Production.

    Sinkūnienė, Dovilė; Adlercreutz, Patrick

    2014-01-01

    Lipase-catalyzed ethanolysis of triolein was studied as a model for biodiesel production. Four lipases were immobilized on porous polypropylene, and ethanolysis reactions were carried out in methyl t-butyl ether. The reaction products were analyzed using gas chromatography. Three of the four lipases studied were efficient in the conversion of triolein to 2-monoolein, but slow in the final step of producing glycerol. However, Candida antarctica lipase B was slow in the conversion of triolein, but more efficient in the subsequent two steps than the other lipases. The 1,3-selectivity of the lipases was less pronounced for the monooleins than for triolein. Silica gel was investigated as a catalyst for acyl migration, showing an increase in biodiesel yield with three of the lipases, but a reduction in yield when C. antarctica lipase B was used. The highest biodiesel yield (96 %) was obtained with a combination of Rhizopus arrhizus lipase and C. antarctica lipase B. PMID:25045169

  8. Molecular characterization of a proteolysis-resistant lipase from Bacillus pumilus SG2

    R. Sangeetha

    2014-06-01

    Full Text Available Proteolysis-resistant lipases can be well exploited by industrial processes which employ both lipase and protease as biocatalysts. A proteolysis resistant lipase from Bacillus pumilus SG2 was isolated, purified and characterized earlier. The lipase was resistant to native and commercial proteases. In the present work, we have characterized the lip gene which encodes the proteolysis-resistant lipase from Bacillus pumilus SG2. The parameters and structural details of lipase were analysed. The lip gene consisted of 650 bp. The experimental molecular weight of SG2 lipase was nearly double that of its theoretical molecular weight, thus suggesting the existence of the functional lipase as a covalent dimer. The proteolytic cleavage sites of the lipase would have been made inaccessible by dimerisation, thus rendering the lipase resistant to protease.

  9. Clinical efficacy of serum lipase subtype analysis for the differential diagnosis of pancreatic and non-pancreatic lipase elevation

    Bang, Chang Seok; Kim, Jin Bong; Park, Sang Hyun; Baik, Gwang Ho; Su, Ki Tae; Yoon, Jai Hoon; Kim, Yeon Soo; Kim, Dong Joon

    2016-01-01

    Background/Aims: Non-pancreatic elevations of serum lipase have been reported, and differential diagnosis is necessary for clinical practice. This study aimed to evaluate the clinical efficacy of serum lipase subtype analysis for the differential diagnosis of pancreatic and non-pancreatic lipase elevation. Methods: Patients who were referred for the serum lipase elevation were prospectively enrolled. Clinical findings and serum lipase subtypes were analyzed and compared by dividing the patients into pancreatitis and non-pancreatitis groups. Results: A total of 34 patients (12 pancreatitis vs. 22 non-pancreatitis cases) were enrolled. In univariate analysis, the fraction of pancreatic lipase (FPL) in the total amount of serum lipase subtypes was statistically higher in patients with pancreatitis ([median, 0.004; interquartile range [IQR], 0.003 to 0.011] vs. [median, 0.002; IQR, 0.001 to 0.004], p = 0.04). Based on receiver operating characteristic curve analysis for the prediction of acute pancreatitis, FPL was the most valuable predictor (area under the receiver-operating characteristic curve [AUROC], 0.72; 95% confidence interval [CI], 0.54 to 0.86; sensitivity, 83.3%; specificity, 63.6%; positive predictive value, 55.6%; negative predictive value, 97.5%). In multivariate analysis, a cut-off value higher than 0.0027 for the FPL was associated with acute pancreatitis (odds ratio, 8.3; 95% CI, 1.3 to 51.7; p = 0.02). Conclusions: The results did not support that serum lipase subtype analysis could replace standard lipase measurement for the diagnosis of acute pancreatitis. However, the test demonstrated adequate sensitivity for use in triage or as an add-on test for serum lipase elevation. PMID:27243230

  10. SIFAT-SIFAT BIOKIMIAWI EKSTRAK KASAR LIPASE EKSTRASELULER DARI BAKTERI Azospirillum sp. JG3

    Puji Lestari; Santi Nur Handayani; Oedjijono

    2009-01-01

    Lipases are valuable biocatalysts because they act under extremely mild conditions, are stable in organic solvents, show broad substrate specificity and exhibit high stereoselectivity. Lipases play important role in various industries such as detergent, cosmetics, flavor, pharmacy and synthesis of organic compounds. The increasing of lipases requirements in industries is goading research to get new lipases resources commited. One of potential lipase resource is Azospirillum sp.JG3 bacteria fr...

  11. Role of adipocyte-derived lipoprotein lipase in adipocyte hypertrophy

    Orlando Robert A

    2007-10-01

    Full Text Available Abstract Background A major portion of available fatty acids for adipocyte uptake is derived from lipoprotein lipase (LPL-mediated hydrolysis of circulating lipoprotein particles. In vivo studies aimed at identifying the precise role of adipocyte-derived LPL in fat storage function of adipose tissue have been unable to provide conclusive evidence due to compensatory mechanisms that activate endogenous fatty acid synthesis. To address this gap in knowledge, we have measured the effect of reducing adipocyte LPL expression on intracellular lipid accumulation using a well-established cultured model of adipocyte differentiation. Methods siRNA specific for mouse LPL was transfected into 3T3-L1 adipocytes. Expression of LPL was measured by quantitative real-time PCR and cell surface-associated LPL enzymatic activity was measured by colorimetric detection following substrate (p-nitrophenyl butyrate hydrolysis. Apolipoprotein CII and CIII expression ratios were also measured by qRT-PCR. Intracellular lipid accumulation was quantified by Nile Red staining. Results During differentiation of 3T3-L1 pre-adipocytes, LPL mRNA expression increases 6-fold resulting in a 2-fold increase in cell surface-associated LPL enzymatic activity. Parallel to this increase in LPL expression, we found that intracellular lipids increased ~10-fold demonstrating a direct correlation between adipocyte-derived LPL expression and lipid storage. We next reduced LPL expression in adipocytes using siRNA transfections to directly quantify the contributions of adipocyte-derived LPL to lipid storage, This treatment reduced LPL mRNA expression and cell surface-associated LPL enzymatic activity to ~50% of non-treated controls while intracellular lipid levels were reduced by 80%. Exogenous addition of purified LPL (to restore extracellular lipolytic activity or palmitate (as a source of free fatty acids to siRNA-treated cells restored intracellular lipid levels to those measured for non

  12. Exercise regulation of adipose tissue.

    Stanford, Kristin I; Goodyear, Laurie J

    2016-01-01

    Exercise training results in adaptations to numerous organ systems and offers protection against metabolic disorders including obesity and type 2 diabetes, and recent reports suggest that adipose tissue may play a role in these beneficial effects of exercise on overall health. Multiple studies have investigated the effects of exercise training on both white adipose tissue (WAT) and brown adipose tissue (BAT), as well as the induction of beige adipocytes. Studies from both rodents and humans show that there are exercise training-induced changes in WAT including decreased cell size and lipid content, and increased mitochondrial activity. In rodents, exercise training causes an increased beiging of WAT. Whether exercise training causes a beiging of human scWAT, as well as which factors contribute to the exercise-induced beiging of WAT are areas of current investigation. Studies investigating the effects of exercise training on BAT mass and function have yielded conflicting data, and hence, is another area of intensive investigation. This review will focus on studies aimed at elucidating the mechanisms regulating exercise training induced-adaptations to adipose tissue. PMID:27386159

  13. Adipose tissue macrophages: amicus adipem?

    Odegaard, Justin I.; Ganeshan, Kirthana; Chawla, Ajay

    2013-01-01

    Chronic overnutrition drives complex adaptations within both professional metabolic and bystander tissues that, despite intense investigation, are still poorly understood. Xu et al. (2013) now describe the unexpected ability of adipose tissue macrophages to buffer lipids released from obese adipocytes in a manner independent of inflammatory macrophage activation.

  14. Quantification of adipose tissue insulin sensitivity

    Søndergaard, Esben; Jensen, Michael D

    2016-01-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute...... to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible...... quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and...

  15. Quantification of adipose tissue insulin sensitivity.

    Søndergaard, Esben; Jensen, Michael D

    2016-06-01

    In metabolically healthy humans, adipose tissue is exquisitely sensitive to insulin. Similar to muscle and liver, adipose tissue lipolysis is insulin resistant in adults with central obesity and type 2 diabetes. Perhaps uniquely, however, insulin resistance in adipose tissue may directly contribute to development of insulin resistance in muscle and liver because of the increased delivery of free fatty acids to those tissues. It has been hypothesized that insulin adipose tissue resistance may precede other metabolic defects in obesity and type 2 diabetes. Therefore, precise and reproducible quantification of adipose tissue insulin sensitivity, in vivo, in humans, is an important measure. Unfortunately, no consensus exists on how to determine adipose tissue insulin sensitivity. We review the methods available to quantitate adipose tissue insulin sensitivity and will discuss their strengths and weaknesses. PMID:27073214

  16. A cold-adapted and organic solvent-tolerant lipase from a psychrotrophic bacterium Pseudomonas sp. strain YY31: identification, cloning, and characterization.

    Yamashiro, Yoko; Sakatoku, Akihiro; Tanaka, Daisuke; Nakamura, Shogo

    2013-10-01

    A novel cold-adapted lipase (designated as LipYY31) was obtained from a psychrotrophic Pseudomonas sp. YY31. The strain YY31 was gram-negative, rod shaped, motile by means of one polar flagellum, and exhibited chemotaxis toward oil droplets under a microscope. The strain displayed remarkable degradation of edible oil and fat even at 5 °C. The LipYY31 DNA fragment contains an open reading frame of 1,410 bp which encoded a protein of 470 amino acids with an estimated molecular mass of 49,584 Da. LipYY31 showed high sequence similarity to those of subfamily Ι.3 lipase and had a conserved GXSXG motif around the catalytic Ser residue. Its optimal temperature was 25-30 °C, and it retained 20-40 % of its activity at 0-5 °C. The optimal pH value was 8.0. The activity was strongly inhibited by Cd(2+), Zn(2+), EDTA and was highly dependent on Ca(2+). Tricaprin and p-nitrophenyl caprate were the most favorable substrates among the triglycerides and p-nitrophenyl esters, respectively. LipYY31 also had high activity towards natural substrates including edible vegetable oils and animal fat. Furthermore, LipYY31 was very active and stable in the presence of several detergents and organic solvents. In particular, the lipase exhibited high stability against organic solvents such as methanol, ethanol, and isopropanol. PMID:23918082

  17. Application of immobilized lipase in nonaqueous synthesis%固定化脂肪酶在非水相合成中的应用

    孙月娥; 王卫东

    2011-01-01

    Lipase can catalyse the hydrolysis of triglycerides at the oil/water interface, but their ability to form ester bonds under reverse hydrolytic conditions enables them to catalyse various other types of reactions such as esterification and transesterification in organic solvents. Now it has been widely used in food, pharmaceutical,cosmetic and detergent industries. As a consequence of their versatility in application, lipases are regarded as enzymes of high commercial potential. Here we reviewed the reaction system, factors influencing the synthesis in non-aqueous media and application of lipase,which provided a promising prospect for further study lipasecatalysed synthesis in non-aqueous media.%脂肪酶是分解脂肪的酶,非水体系可促使反应平衡逆向进行,因而脂肪酶又具有合成功能.目前非水相脂肪酶催化合成技术在食品、医药、化妆品等多个领域中都有广泛的应用.本文对非水相中脂肪酶的反应体系、影响非水相酶促反应的因素以及其应用领域进行了综述,对于深入研究非水体系中脂肪酶催化的合成反应具有较强的参考价值.

  18. The Lp_3561 and Lp_3562 Enzymes Support a Functional Divergence Process in the Lipase/Esterase Toolkit from Lactobacillus plantarum

    Esteban-Torres, María; Reverón, Inés; Santamaría, Laura; Mancheño, José M.; de las Rivas, Blanca; Muñoz, Rosario

    2016-01-01

    Lactobacillus plantarum species is a good source of esterases since both lipolytic and esterase activities have been described for strains of this species. No fundamental biochemical difference exists among esterases and lipases since both share a common catalytic mechanism. L. plantarum WCFS1 possesses a protein, Lp_3561, which is 44% identical to a previously described lipase, Lp_3562. In contrast to Lp_3562, Lp_3561 was unable to degrade esters possessing a chain length higher than C4 and the triglyceride tributyrin. As in other L. plantarum esterases, the electrostatic potential surface around the active site in Lp_3561 is predicted to be basic, whereas it is essentially neutral in the Lp_3562 lipase. The fact that the genes encoding both proteins were located contiguously in the L. plantarum WCFS1 genome, suggests that they originated by tandem duplication, and therefore are paralogs as new functions have arisen during evolution. The presence of the contiguous lp_3561 and lp_3562 genes was studied among L. plantarum strains. They are located in a 8,903 bp DNA fragment that encodes proteins involved in the catabolism of sialic acid and are predicted to increase bacterial adaptability under certain growth conditions. PMID:27486450

  19. Expression and properties of three novel fungal lipases/sterol esterases predicted in silico: comparison with other enzymes of the Candida rugosa-like family.

    Vaquero, María Eugenia; Prieto, Alicia; Barriuso, Jorge; Martínez, María Jesús

    2015-12-01

    Lipases from the Candida rugosa-like family are enzymes with great biotechnological interest. In a previous work, several enzymes from this family were identified by in silico mining of fungal genomes. Here, we describe the cloning, expression, and characterization of putative lipases from the genomes of Nectria haematococca, Trichoderma reesei, and Aspergillus niger and compared their catalytic properties with those of OPE, a well-characterized sterol esterase/lipase from Ophiostoma piceae. All of them hydrolyzed p-nitrophenol esters and triglycerides with different efficiency, but their activity against sterol esters was dissimilar, and the enzyme from A. niger was unable of hydrolyzing these substrates while OPE showed the best k cat values, which in general leads to an improved catalytic efficiency. Similarly, OPE was the best catalyst in the synthesis of β-sitostanyl oleate, followed by the commercial CRL from C. rugosa, while the A. niger enzyme was unable to produce this compound. When the enzymes were evaluated for caprolactone oligomerization, the A. niger enzyme gave similar results than CRL, being OPE slightly more efficient. The expression of the putative selected proteins allowed their functional validation, suggesting that the hydrophobicity of the lid region may be an important factor, although the enzymatic efficiency is also influenced by other parameters, as the aggregation state and the size and morphology of the tunnel, where substrate recognition and catalysis takes place. PMID:26272094

  20. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  1. Fetal and neonatal exposure to nicotine leads to augmented hepatic and circulating triglycerides in adult male offspring due to increased expression of fatty acid synthase

    Ma, Noelle [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Nicholson, Catherine J. [Department of Obstetrics and Gynecology, McMaster University (Canada); Wong, Michael [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada); Holloway, Alison C. [Department of Obstetrics and Gynecology, McMaster University (Canada); Hardy, Daniel B., E-mail: Daniel.Hardy@schulich.uwo.ca [Department of Physiology and Pharmacology, The University of Western Ontario (Canada); Department of Obstetrics and Gynecology, The University of Western Ontario (Canada); The Children' s Health Research Institute, The University of Western Ontario (Canada); The Lawson Health Research Institute, The University of Western Ontario (Canada)

    2014-02-15

    While nicotine replacement therapy is assumed to be a safer alternative to smoking during pregnancy, the long-term consequences for the offspring remain elusive. Animal studies now suggest that maternal nicotine exposure during perinatal life leads to a wide range of adverse outcomes for the offspring including increased adiposity. The focus of this study was to investigate if nicotine exposure during pregnancy and lactation leads to alterations in hepatic triglyceride synthesis. Female Wistar rats were randomly assigned to receive daily subcutaneous injections of saline (vehicle) or nicotine bitartrate (1 mg/kg/day) for two weeks prior to mating until weaning. At postnatal day 180 (PND 180), nicotine exposed offspring exhibited significantly elevated levels of circulating and hepatic triglycerides in the male offspring. This was concomitant with increased expression of fatty acid synthase (FAS), the critical hepatic enzyme in de novo triglyceride synthesis. Given that FAS is regulated by the nuclear receptor Liver X receptor (LXRα), we measured LXRα expression in both control and nicotine-exposed offspring. Nicotine exposure during pregnancy and lactation led to an increase in hepatic LXRα protein expression and enriched binding to the putative LXRE element on the FAS promoter in PND 180 male offspring. This was also associated with significantly enhanced acetylation of histone H3 [K9,14] surrounding the FAS promoter, a hallmark of chromatin activation. Collectively, these findings suggest that nicotine exposure during pregnancy and lactation leads to an increase in circulating and hepatic triglycerides long-term via changes in the transcriptional and epigenetic regulation of the hepatic lipogenic pathway. - Highlights: • Our data reveals the links nicotine exposure in utero and long-term hypertriglyceridemia. • It is due to nicotine-induced augmented expression of hepatic FAS and LXRα activity. • Moreover, this involves nicotine-induced enhanced

  2. Enzymatic activity of lipase in post-metamorphic phase bullfrogs

    Braga Luís Gustavo Tavares

    2006-01-01

    Full Text Available The knowledge of the digestive system of bullfrogs is an important step for the determination of their nutritional requirements throughout growth phases. With the objective of evaluating the enzymatic activity of lipase in the intestinal content of bullfrogs (Rana catesbeiana Shaw, 1802, 100 animals with median weight of 3.6 g were distributed in stalls under controlled temperature and photoperiod. The frogs, selected at the post-metamorphic phase, received commercial extruded diet ad libitum throughout the 87-day experiment. The collections of the intestinal content were performed by the desensitization of the frogs in ice and water at 0ºC and subsequent isolation of the small intestine. Determination of lipase activity was performed with a commercial enzymatic kit (Lipase-Bioclin, MG, Brazil, first measured in samples taken at day three (3.46 UI. During the initial phase the bullfrog possesses low lipase hydrolysis capacity was found, having a specific activity of 217 UI mg-1. In the subsequent period both lipase activity and specific lipase activity continuously increased. Lipase activity as a function of bullfrog weight fell after day twenty and reached 0.33 UI g-1, for frogs of medium weight (179 g. Feed for bullfrogs at the post-metamorphic phase weighing more than 10 g can have larger amounts of ingredients containg lipids, due to the increased digestive capacity of these frogs.

  3. Parenteral use of medium-chain triglycerides: a reappraisal.

    Ulrich, H; Pastores, S M; Katz, D P; Kvetan, V

    1996-04-01

    Over the last two decades, the clinical use of intravenous fat emulsions for the nutritional support of hospitalized patients has become routine. During this time long-chain triglycerides (LCT) derived from soybean and/or safflower oils were the exclusive lipid source for these emulsions, providing both a safe calorically dense alternative to dextrose and essential fatty acids needed for biologic membranes and the maintenance of immune function. During the past decade, the availability of novel experimental triglycerides for parenteral use has generated interest in the use of these substrates for nutritional and metabolic support. Medium-chain triglycerides (MCT), long advocated as a superior substrate for parenteral use, possess many unique physiochemical and metabolic properties that make them theoretically advantageous over their LCT counterparts. Although not yet approved in the United States, preparations containing MCT have been widely available in Europe. Intravenous MCT preparations, either as physical mixtures or structured lipids, have been used clinically in patients with immunosuppresion, critical illness, liver and pulmonary disease and in premature infants. Despite great promise, the clinical data comparing the efficacy of MCT-based lipid emulsions to their LCT counterparts has been equivocal. This may be due in part to the limited nature of the published clinical trials. Measures of efficacy for parenteral or enteral nutritional products has taken on new meaning, in light of the reported experience using immunomodulatory nutrients. Current concerns about cost of medical care and resource use warrant careful deliberation about the utility of any new and expensive therapy. Until clinical data can fulfill expectations derived from animal studies, it is difficult to advocate the general use of MCT-based lipid emulsions. Future clinical studies with MCT-based emulsions should have clear outcome objectives sufficient to prove their theorized metabolic

  4. Triglyceride profile in dyslipidemia of type 2 diabetes mellitus

    To evaluate ratios of serum triglycerides and cholesterol levels which may indicate postprandial lipid handling and to assess their role as prospective markers of dyslipidaemia in type 2 diabetes mellitus. The study comprised 160 subjects, including 83 known type 2 diabetics (45 males, 38 females) and 77 age-matched controls (45 males, 32 females). Fasting blood samples were analysed for serum triglycerides and total cholesterol, using automated chemistry analyzer. HDL-C was determined by precipitation method and LDL-C and VLDL-C were estimated by Friedewalds formula. LDL/HDL ratio and TG/HDL ratios were also calculated. The mean values for male and female diabetics were compared with that for the male and female non-diabetics respectively and tested for significance by paired t-test. Serum triglycerides and VLDL were raised in both male and female diabetics. No significant differences were observed in levels of serum total cholesterol, LDL, HDL and the LDL/HDL ratio. The mean value of the TG/HDL ratio for male diabetics was higher than that for the male non-diabetics (p=0.39). A statistically significant difference was found in the TG/HDL ratios for the female diabetics and non-diabetics (p<0.05). In this study, type 2 diabetics showed marked hypertriglyceridaemia and raised TG/HDL ratio. The dyslipidaemia of diabetes predisposes to development of coronary heart disease and therefore, evaluation of the TG:HDL ratio may provide a good tool to monitor and manage the lipid abnormalities in diabetics. (author)

  5. Pancreatic Lipase Inhibitory Effects of Mangosteen Pericarps

    Xinjie Lin

    2014-03-01

    Full Text Available Pancreatic lipase plays a key role in the digestion and absorption of lipids, inhibition of Pancreatic Lipase (PL is considered as a new approach to obesity treatment. The objective of the present study was to find PL inhibitors from natural food sources. Eighteen natural food products sampled from local supermarkets in Zhuhai were tested for PL inhibitory activity using a copper-soap photometric method. Among the samples tested, the crude extracts from mangosteen pericarp, lemon pulp, celery, cucumber and dry longan were found to be able to suppress the PL activity to different extents, while dry red chili, fresh green chili and dry clove exhibited a promotion effect on the PL. Shiitake mushroom, green bell pepper, lemon peel and spices (ginger, oregano leaf, bay leaf, cinnamon and dry tangerine showed no significant influence either on the inhibition or promotion. The crude extract of mangosteen pericarp was further fractioned to trace active fractions. It was found that the n-butanol fraction was the major contributor to the PL-inhibitory effect of mangosteen pericarp and the inhibition rate was 43.9% at the concentration of 1 mg/mL, the IC50 value was 0.918 mg/mL. Mangosteen pericarp is worthy of utilization as functional food constituents for the prevention and treatment of obesity.

  6. The role of porous nanostructure in controlling lipase-mediated digestion of lipid loaded into silica particles.

    Joyce, Paul; Tan, Angel; Whitby, Catherine P; Prestidge, Clive A

    2014-03-18

    The rate and extent of lipolysis, the breakdown of fat into molecules that can be absorbed into the bloodstream, depend on the interfacial composition and structure of lipid (fat) particles. A novel method for controlling the interfacial properties is to load the lipid into porous colloidal particles. We report on the role of pore nanostructure and surface coverage in controlling the digestion kinetics of medium-chain and long-chain triglycerides loaded into porous silica powders of different particle size, porosity, and hydrophobicity/hydrophilicity. An in vitro lipolysis model was used to measure digestion kinetics of lipid by pancreatic lipase, a digestive enzyme. The rate and extent of lipid digestion were significantly enhanced when a partial monolayer of lipid was loaded in porous hydrophilic silica particles compared to a submicrometer lipid-in-water emulsion or a coarse emulsion. The inhibitory effect of digestion products was clearly evident for digestion from a submicrometer emulsion and coarse emulsion. This effect was minimal, however, in the two silica-lipid systems. Lipase action was inhibited for lipid loaded in the hydrophobic silica and considered due to the orientation of lipase adsorption on the methylated silica surface. Thus, hydrophilic silica promotes enhanced digestion kinetics, whereas hydrophobic silica exerts an inhibitory effect on hydrolysis. Evaluation of digestion kinetics enabled the mechanism for enhanced rate of lipolysis in silica-lipid systems to be derived and detailed. These investigations provide valuable insights for the optimization of smart food microparticles and lipid-based drug delivery systems based on lipid excipients and porous nanoparticles. PMID:24552363

  7. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    Yang, Yanbo; Thyagarajan, Narmadaa; Coady, Breanne M.; Brown, Robert J., E-mail: rbrown@mun.ca

    2014-09-05

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL.

  8. Cholesterol efflux from THP-1 macrophages is impaired by the fatty acid component from lipoprotein hydrolysis by lipoprotein lipase

    Highlights: • Lipoprotein hydrolysis products were produced by lipoprotein lipase. • Hydrolysis products lowers expression of macrophage cholesterol transporters. • Hydrolysis products reduces expression of select nuclear receptors. • Fatty acid products lowers cholesterol transporters and select nuclear receptors. • Fatty acid products reduces cholesterol efflux from macrophages. - Abstract: Lipoprotein lipase (LPL) is an extracellular lipase that primarily hydrolyzes triglycerides within circulating lipoproteins. Macrophage LPL contributes to atherogenesis, but the mechanisms behind it are poorly understood. We hypothesized that the products of lipoprotein hydrolysis generated by LPL promote atherogenesis by inhibiting the cholesterol efflux ability by macrophages. To test this hypothesis, we treated human THP-1 macrophages with total lipoproteins that were hydrolyzed by LPL and we found significantly reduced transcript levels for the cholesterol transporters ATP binding cassette transporter A1 (ABCA1), ABCG1, and scavenger receptor BI. These decreases were likely due to significant reductions for the nuclear receptors liver-X-receptor-α, peroxisome proliferator activated receptor (PPAR)-α, and PPAR-γ. We prepared a mixture of free fatty acids (FFA) that represented the ratios of FFA species within lipoprotein hydrolysis products, and we found that the FFA mixture also significantly reduced cholesterol transporters and nuclear receptors. Finally, we tested the efflux of cholesterol from THP-1 macrophages to apolipoprotein A-I, and we found that the treatment of THP-1 macrophages with the FFA mixture significantly attenuated cholesterol efflux. Overall, these data show that the FFA component of lipoprotein hydrolysis products generated by LPL may promote atherogenesis by inhibiting cholesterol efflux, which partially explains the pro-atherogenic role of macrophage LPL

  9. Triglyceride-Rich Lipoproteins and Atherosclerotic Cardiovascular Disease

    Nordestgaard, Børge G

    2016-01-01

    Scientific interest in triglyceride-rich lipoproteins has fluctuated over the past many years, ranging from beliefs that these lipoproteins cause atherosclerotic cardiovascular disease (ASCVD) to being innocent bystanders. Correspondingly, clinical recommendations have fluctuated from a need.......1-fold for myocardial infarction, 3.2-fold for ischemic heart disease, 3.2-fold for ischemic stroke, and 2.2-fold for all-cause mortality. Also, genetic studies using the Mendelian randomization design, an approach that minimizes problems with confounding and reverse causation, now demonstrate...

  10. Synthesis and characterization of triglyceride based thermosetting polymers

    Can, Erde

    2005-07-01

    Plant oils, which are found in abundance in all parts of the world and are easily replenished annually, have the potential to replace petroleum as a chemical feedstock for making polymers. Within the past few years, there has been growing interest to use triglycerides as the basic constituent of thermosetting polymers with the necessary rigidity, strength and glass transition temperatures required for engineering applications. Plant oils are not polymerizable in their natural form, however various functional groups that can polymerize can easily be attached to the triglyceride structure making them ideal cross-linking monomers for thermosetting liquid molding resins. Through this research project a number of thermosetting liquid molding resins based on soybean and castor oil, which is a specialty oil with hydroxyls on its fatty acids, have been developed. The triglyceride based monomers were prepared via the malination of the alcoholysis products of soybean and castor oil with various polyols, such as pentaerythritol, glycerol, and Bisphenol A propoxylate. The malinated glycerides were then cured in the presence of a reactive diluent, such as styrene, to form rigid glassy materials with a wide range of properties. In addition to maleate half-esters, methacrylates were also introduced to the glyceride structure via methacrylation of the soybean oil glycerolysis product with methacrylic anhydride. This product, which contains methacrylic acid as by-product, and its blends with styrene also gave rigid materials when cured. The triglyceride based monomers were characterized via conventional spectroscopic techniques. Time resolved FTIR analysis was used to determine the curing kinetics and the final conversions of polymerization of the malinated glyceride-styrene blends. Dynamic Mechanical Analysis (DMA) was used to determine the thermomechanical behavior of these polymers and other mechanical properties were determined via standard mechanical tests. The use of lignin

  11. A Newly Isolated Thermostable Lipase from Bacillus sp.

    Abu Bakar Salleh

    2011-05-01

    Full Text Available A thermophilic lipolytic bacterium identified as Bacillus sp. L2 via 16S rDNA was previously isolated from a hot spring in Perak, Malaysia. Bacillus sp. L2 was confirmed to be in Group 5 of bacterial classification, a phylogenically and phenotypically coherent group of thermophilic bacilli displaying very high similarity among their 16S rRNA sequences (98.5–99.2%. Polymerase chain reaction (PCR cloning of L2 lipase gene was conducted by using five different primers. Sequence analysis of the L2 lipase gene revealed an open reading frame (ORF of 1251 bp that codes for 417 amino acids. The signal peptides consist of 28 amino acids. The mature protein is made of 388 amino acid residues. Recombinant lipase was successfully overexpressed with a 178-fold increase in activity compared to crude native L2 lipase. The recombinant L2 lipase (43.2 kDa was purified to homogeneity in a single chromatography step. The purified lipase was found to be reactive at a temperature range of 55–80 °C and at a pH of 6–10. The L2 lipase had a melting temperature (Tm of 59.04 °C when analyzed by circular dichroism (CD spectroscopy studies. The optimum activity was found to be at 70 °C and pH 9. Lipase L2 was strongly inhibited by ethylenediaminetetraacetic acid (EDTA (100%, whereas phenylmethylsulfonyl fluoride (PMSF, pepstatin-A, 2-mercaptoethanol and dithiothreitol (DTT inhibited the enzyme by over 40%. The CD spectra of secondary structure analysis showed that the L2 lipase structure contained 38.6% α-helices, 2.2% ß-strands, 23.6% turns and 35.6% random conformations.

  12. 脂蛋白脂酶缺失症基因治疗载体的构建及功能验证%Construction and Verification of Gene Therapy Vector for Lipoprotein Lipase Deficiency Disease

    王恺龙; 郑李彬; 张帆; 沈良才; Libby Andrew; 李旭丽; 张瑾

    2013-01-01

    脂蛋白脂酶(lipoprotein lipase,LPL)是甘油三酯分解的限速酶,LPL基因缺失会引起高血脂症,虽然发病率低,但到目前为止,尚无有效治疗手段.该文构建了用于纠正LPL缺失基因型的逆转录病毒载体MSCV-hLPL,结果表明,MSCV-hLPL可以高效侵染体外培养的细胞系C2C12、HEK293和3T3-L1,并且都可以产生具有活性的脂蛋白脂酶.利用MSCV-hLPL侵染后的C2C12、HEK293和3T3-L1,分别注射到裸鼠皮下组织,发现C2C12和3T3-L1可以分泌脂蛋白脂酶到临近的肌肉组织中,显著提高LPL活性.以上工作证明,基因治疗载体可以纠正脂蛋白脂酶缺失的基因型,而脂肪细胞和肌肉细胞移植入裸鼠体内后,均可以作为生物反应器产生具有活性的LPL.这是该领域中的一次开拓性尝试,为脂蛋白脂酶缺失症治疗方法的开发打下了坚实的基础.%Lipoprotein lipase (LPL) is the rate limiting enzyme for triglycerides hydrolysis,which catalyses the hydrolysis of the triacylglycerol component of chylomicrons and very low density lipoproteins,thereby providing fatty acids and monoacylglycerol for tissue utilization.LPL gene mutation or deletion may affect the activity of LPL,and result in lipid metabolism disorder.Although the LPL deficiency disease is rare,no cure method is developed till now.In this study,the gene therapy construct MSCV-hLPL was made,which could infect muscle cell line (C2C12),kidney cell line (HEK293T) and pre-adipocyte cell line (3T3-L1) with over 80% efficiency.Nevertheless,active LPL could be detected at the surface of all these three kinds of cells.Then,three types of cells were injected into nude mice,LPL activity increased significantly in the muscle tissues under the injection sites of the 3T3-L1 line.Our results show that MSCV-hLPL could correct the LPL-/-genotype and the adipose tissue may be the best tissue for transplantation in the future.This is a ground-breaking test in LPL deficiency treatment field

  13. Endothelial and lipoprotein lipases in human and mouse placenta

    Lindegaard, Marie Louise Skakkebæk; Olivecrona, Gunilla; Christoffersen, Christina;

    2005-01-01

    protein associated with both cell types. In mouse placentas, lack of LPL expression resulted in increased EL mRNA expression. These results suggest that the cellular expression of EL and LPL in human placenta is different. Nevertheless, the two lipases might have overlapping functions in the mouse......Placenta expresses various lipase activities. However, a detailed characterization of the involved genes and proteins is lacking. In this study, we compared the expression of endothelial lipase (EL) and LPL in human term placenta. When placental protein extracts were separated by heparin...... placenta. Our data also suggest that the major portions of both proteins are stored in an inactive form in human term placenta....

  14. Gamma-irradiation sterilization of lipases for cheese making

    The possibility of sterilizing the enzyme compounds of lipases from Oospora fragrans strains by gamma irradiation was studied. The enzyme compounds were exposed to gamma irradiation at the doses from 0.1 to 0.8 Mrad with the discreteness of 0.1 Mrad and at the dose of 2.0 Mrad. After the radiation treatment the lipases were investigated for bacterial invasion by the cultivation method and for the lipolytic activity by the titrometrical method. It is shown that the sterilization effect is achieved without losses of lipase activity and the radiation dose necessary for sterilization depends on initial invasion levels in the enzyme compounds

  15. Stability of Surfactant—coated Candida Rugosa Lipase in Isooctane

    宋宝东; 邢爱华; 吴金川; 王世昌

    2003-01-01

    The stability of Candida rugosa lipase coated with glutamic acid didodecyl ester ribitol amide was investigated taking esterification of lauryl alcohol and lauric acid in isooctane as a model reaction.At 30℃,the half-life of the activity of the coated lipase was ca 10h,the enzyme activity became less changed after 12h and the residual activity was 39% of the initial value ,The coated lipase obeyed a first-order deactivation model with a deactivation energy of 29.9 J.mol-1.

  16. Acute Pancreatitis with Normal Serum Lipase: A Case Series

    Anish M Shah

    2010-07-01

    Full Text Available Context Acute pancreatitis is diagnosed on the basis of clinical features, biochemical tests and imaging studies. Normal serum amylase level has been reported in the setting of acute pancreatitis but normal serum lipase level in acute pancreatitis is extremely rare. Case report Herein, we present a case series of acute pancreatitis with normal serum lipase levels along with a review of the topic. Conclusion In appropriate clinical setting, the diagnosis of acute pancreatitis should be entertained even with normal serum amylase and lipase levels.

  17. Mechanism of bacteriophage conversion of lipase activity in Staphylococcus aureus.

    Lee, C Y; Iandolo, J J

    1985-01-01

    Staphylococcus aureus PS54 harbors two temperate bacteriophages and manifests no lipase activity on egg yolk agar. Curing of one of the resident prophages (L54a) restores lipase activity. To study the mechanism of bacteriophage conversion, the prophage was cured, and the gene encoding lipase activity was cloned into pBR322 in Escherichia coli on a 2.9-kilobase DNA fragment of the chromosome. The fragment was subcloned into a shuttle vector and subsequently transformed into S. aureus and Bacil...

  18. Superparamagnetic nanotraps containing MIP based mimic lipase for biotransformations uses

    The nanoparticle comprises a superparamagnetic iron oxide nanoparticle core conjugated with trimethoxylsilyl propylmethacrylate (TMSPM) and methacryloylamido serine (MASE), methacryloylamido histidine (MAH), methacryloylamido glutamic acid (MAGA) monomers, and p-nitrophenyl palmitate (p-NPP) which is a substrate of lipase as a template molecule, which enables the creation of lipase active region. The resulting hybrid superparamagnetic nanotraps are magnetically separable, highly active, and stable under harsh conditions. In this study, the advantages of high selectivity of molecular imprinting technique have used to get mimic lipase for the synthesis of methyl jasmonate and methyl oleate.

  19. The Role of Adiposity in Cardiometabolic Traits: A Mendelian Randomization Analysis

    Ploner, Alexander; Fischer, Krista; Horikoshi, Momoko; Sarin, Antti-Pekka; Thorleifsson, Gudmar; Ladenvall, Claes; Kals, Mart; Kuningas, Maris; Draisma, Harmen H. M.; Ried, Janina S.; van Zuydam, Natalie R.; Huikari, Ville; Mangino, Massimo; Sonestedt, Emily; Benyamin, Beben; Nelson, Christopher P.; Rivera, Natalia V.; Kristiansson, Kati; Shen, Huei-yi; Havulinna, Aki S.; Dehghan, Abbas; Donnelly, Louise A.; Kaakinen, Marika; Nuotio, Marja-Liisa; Robertson, Neil; de Bruijn, Renée F. A. G.; Ikram, M. Arfan; Amin, Najaf; Balmforth, Anthony J.; Braund, Peter S.; Doney, Alexander S. F.; Döring, Angela; Elliott, Paul; Esko, Tõnu; Franco, Oscar H.; Gretarsdottir, Solveig; Hartikainen, Anna-Liisa; Heikkilä, Kauko; Herzig, Karl-Heinz; Holm, Hilma; Hottenga, Jouke Jan; Hyppönen, Elina; Illig, Thomas; Isaacs, Aaron; Isomaa, Bo; Karssen, Lennart C.; Kettunen, Johannes; Koenig, Wolfgang; Kuulasmaa, Kari; Laatikainen, Tiina; Laitinen, Jaana; Lindgren, Cecilia; Lyssenko, Valeriya; Läärä, Esa; Rayner, Nigel W.; Männistö, Satu; Pouta, Anneli; Rathmann, Wolfgang; Rivadeneira, Fernando; Ruokonen, Aimo; Savolainen, Markku J.; Sijbrands, Eric J. G.; Small, Kerrin S.; Smit, Jan H.; Steinthorsdottir, Valgerdur; Syvänen, Ann-Christine; Taanila, Anja; Tobin, Martin D.; Uitterlinden, Andre G.; Willems, Sara M.; Willemsen, Gonneke; Witteman, Jacqueline; Perola, Markus; Evans, Alun; Ferrières, Jean; Virtamo, Jarmo; Kee, Frank; Tregouet, David-Alexandre; Arveiler, Dominique; Amouyel, Philippe; Ferrario, Marco M.; Brambilla, Paolo; Hall, Alistair S.; Heath, Andrew C.; Madden, Pamela A. F.; Martin, Nicholas G.; Montgomery, Grant W.; Whitfield, John B.; Jula, Antti; Knekt, Paul; Oostra, Ben; van Duijn, Cornelia M.; Penninx, Brenda W. J. H.; Davey Smith, George; Kaprio, Jaakko; Samani, Nilesh J.; Gieger, Christian; Peters, Annette; Wichmann, H.-Erich; Boomsma, Dorret I.; de Geus, Eco J. C.; Tuomi, TiinaMaija; Power, Chris; Hammond, Christopher J.; Spector, Tim D.; Lind, Lars; Orho-Melander, Marju; Palmer, Colin Neil Alexander; Morris, Andrew D.; Groop, Leif; Järvelin, Marjo-Riitta; Salomaa, Veikko; Vartiainen, Erkki; Hofman, Albert; Ripatti, Samuli; Metspalu, Andres; Thorsteinsdottir, Unnur; Stefansson, Kari; Pedersen, Nancy L.; McCarthy, Mark I.; Ingelsson, Erik; Prokopenko, Inga

    2013-01-01

    Background The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach. Methods and Findings We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV) for body mass index (BMI) in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i) rs9939609 and BMI (n = 198,502), (ii) rs9939609 and 24 traits, and (iii) BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI–trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03–1.39) and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1–1.4; all p<0.05). For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p<0.05). The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational

  20. The role of adiposity in cardiometabolic traits: a Mendelian randomization analysis.

    Tove Fall

    Full Text Available The association between adiposity and cardiometabolic traits is well known from epidemiological studies. Whilst the causal relationship is clear for some of these traits, for others it is not. We aimed to determine whether adiposity is causally related to various cardiometabolic traits using the Mendelian randomization approach.We used the adiposity-associated variant rs9939609 at the FTO locus as an instrumental variable (IV for body mass index (BMI in a Mendelian randomization design. Thirty-six population-based studies of individuals of European descent contributed to the analyses. Age- and sex-adjusted regression models were fitted to test for association between (i rs9939609 and BMI (n  =  198,502, (ii rs9939609 and 24 traits, and (iii BMI and 24 traits. The causal effect of BMI on the outcome measures was quantified by IV estimators. The estimators were compared to the BMI-trait associations derived from the same individuals. In the IV analysis, we demonstrated novel evidence for a causal relationship between adiposity and incident heart failure (hazard ratio, 1.19 per BMI-unit increase; 95% CI, 1.03-1.39 and replicated earlier reports of a causal association with type 2 diabetes, metabolic syndrome, dyslipidemia, and hypertension (odds ratio for IV estimator, 1.1-1.4; all p < 0.05. For quantitative traits, our results provide novel evidence for a causal effect of adiposity on the liver enzymes alanine aminotransferase and gamma-glutamyl transferase and confirm previous reports of a causal effect of adiposity on systolic and diastolic blood pressure, fasting insulin, 2-h post-load glucose from the oral glucose tolerance test, C-reactive protein, triglycerides, and high-density lipoprotein cholesterol levels (all p < 0.05. The estimated causal effects were in agreement with traditional observational measures in all instances except for type 2 diabetes, where the causal estimate was larger than the observational estimate (p  =  0

  1. Monoglyceride and diglyceride production through lipase-catalyzed glycerolysis and molecular distillation.

    Fregolente, Patricia Bogalhos Lucente; Pinto, Gláucia Maria F; Wolf-Maciel, Maria Regina; Filho, Rubens Maciel

    2010-04-01

    Distilled glycerides are obtained through distillation of the system mono-diglycerides which is produced from the esterification reaction between a triglyceride with glycerol. In this work, monoglycerides (MG) and diglycerides (DG) are produced through lipase-catalyzed glycerolysis of soybean oil using Candida antarctica B in a solvent-free system. To separate the products of the reaction in order to obtain essentially MG and an oil of DG, it is necessary to use a suitable process in order to preserve the stability of the components and to keep the products free of inappropriate solvents. So, after 24 h of enzymatic reaction, the mixture of acylglycerols and fatty acids was distilled into a centrifugal molecular distiller, since it provides a free solvent and lower temperature environment to increase the desired product concentration. Starting from a material with 25.06% of triglycerides (TG), 46.63% of DG, 21.72% of MG, 5.38% of free fatty acids (FFA), and 1.21% of glycerol, the MG purity in the distillate stream was 80% at evaporator temperature (T (E)) equal to 250 degrees C and feed flow rate (Q) equal to 10.0 mL/min. At these conditions, the MG recovery was 35%. The material collected in the residue stream presented DG-enriched oil with TG unhydrolyzed, residual MG, and low acidity (29.83% of TG, 53.20% of DG, 15.64% of MG, and 1.33% of FFA), which is suitable to replace TG oil in the human diet. PMID:19862491

  2. Maternal exposure to di-(2-ethylhexyl) phthalate exposure deregulates blood pressure, adiposity, cholesterol metabolism and social interaction in mouse offspring.

    Lee, Kuan-I; Chiang, Chin-Wei; Lin, Hui-Ching; Zhao, Jin-Feng; Li, Cheng-Ta; Shyue, Song-Kun; Lee, Tzong-Shyuan

    2016-05-01

    Long-term exposure to di-(2-ethylhexyl) phthalate (DEHP) is highly associated with carcinogenicity, fetotoxicity, psychological disorders and metabolic diseases, but the detrimental effects and mechanisms are not fully understood. We investigated the effect of exposing mouse mothers to DEHP, and the underlying mechanism, on blood pressure, obesity and cholesterol metabolism as well as psychological and learning behaviors in offspring. Tail-cuff plethysmography was used for blood pressure measurement; Western blot used was for phosphorylation and expression of protein; hematoxylin and eosin staining, Nissl staining and Golgi staining were used for histological examination. The serum levels of cholesterol, triglycerides and glucose were measured by blood biochemical analysis. Hepatic cholesterol and triglyceride levels were assessed by colorimetric assay kits. Offspring behaviors were evaluated by open-field activity, elevated plus maze, social preference test and Morris water maze. Maternal DEHP exposure deregulated the phosphorylation of endothelial nitric oxide synthase and upregulated angiotensin type 1 receptor in offspring, which led to increased blood pressure. It led to obesity in offspring by increasing the size of adipocytes in white adipose tissue and number of adipocytes in brown adipose tissue. It increased the serum level of cholesterol in offspring by decreasing the hepatic capacity for cholesterol clearance. The impaired social interaction ability induced by maternal DEHP exposure might be due to abnormal neuronal development. Collectively, our findings provide new evidence that maternal exposure to DEHP has a lasting effect on the physiological functions of the vascular system, adipose tissue and nerve system in offspring. PMID:25995009

  3. CT-demonstration of adipose tissue of the sinus cavernosus

    Adipose bodies of the sinus cavernosus - the only genuine intracranial adipose tissue - can be demonstrated well by CT. They appear as polymorph well defined hypodense objects in unilateral or bilateral manifestation. Adipose bodies most frequently show a size between 4 and 9 mm and densities about -20 to -40 HE. Occasionally the adipose bodies directly lead into the adipose tissue of the orbit. (orig.)

  4. Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction

    Marco Calogero Amato

    2014-01-01

    Full Text Available The Visceral Adiposity Index (VAI has recently proven to be an indicator of adipose distribution and function that indirectly expresses cardiometabolic risk. In addition, VAI has been proposed as a useful tool for early detection of a condition of cardiometabolic risk before it develops into an overt metabolic syndrome. The application of the VAI in particular populations of patients (women with polycystic ovary syndrome, patients with acromegaly, patients with NAFLD/NASH, patients with HCV hepatitis, patients with type 2 diabetes, and general population has produced interesting results, which have led to the hypothesis that the VAI could be considered a marker of adipose tissue dysfunction. Unfortunately, in some cases, on the same patient population, there is conflicting evidence. We think that this could be mainly due to a lack of knowledge of the application limits of the index, on the part of various authors, and to having applied the VAI in non-Caucasian populations. Future prospective studies could certainly better define the possible usefulness of the VAI as a predictor of cardiometabolic risk.

  5. Influence of the dietary intake of medium chain triglycerides on body composition, energy expenditure and satiety: a systematic review Influencia de la ingesta dietética de los triglicéridos de cadena media sobre la composición corporal, el gasto energético y la saciedad: una revisión sistemática

    A. C. Rego Costa; E. L. Rosado; M. Soares-Mota

    2012-01-01

    Increased prevalence of obesity is associated with the growth of chronic degenerative diseases. One of the main factors associated with this increase is the change in nutritional status of individuals. Medium chain triglycerides (MCT) are rapidly metabolized and less stored in the adipose tissue, being a possible tool for weight control. In order to analyze the influence of consumption of this lipid on satiety, body composition and energy expenditure (EE), a literature review was performed of...

  6. Spontaneous hypertension occurs with adipose tissue dysfunction in perilipin-1 null mice.

    Zou, Liangqiang; Wang, Weiyi; Liu, Shangxin; Zhao, Xiaojing; Lyv, Ying; Du, Congkuo; Su, Xueying; Geng, Bin; Xu, Guoheng

    2016-02-01

    Perilipin-1 (Plin1) coats lipid droplets exclusively in adipocytes and regulates two principle functions of adipose tissue, triglyceride storage and hydrolysis, which are disrupted upon Plin1 deficiency. In the present study, we investigated the alterations in systemic metabolites and hormones, vascular function and adipose function in spontaneous hypertensive mice lacking perilipin-1 (Plin1-/-). Plin1-/- mice developed spontaneous hypertension without obvious alterations in systemic metabolites and hormones. Plin1 expressed only in adipose cells but not in vascular cells, so its ablation would have no direct effect in situ on blood vessels. Instead, Plin1-/- mice showed dysfunctions of perivascular adipose tissue (PVAT), a fat depot that anatomically surrounds systemic arteries and has an anticontractile effect. In Plin1-/- mice, aortic and mesenteric PVAT were reduced in mass and adipocyte derived relaxing factor secretion, but increased in basal lipolysis, angiotensin II secretion, macrophage infiltration and oxidative stress. Such multiple culprits impaired the anticontractile effect of PVAT to promote vasoconstriction of aortic and mesenteric arteries of Plin1-/- mice. Furthermore, arterial vessels of Plin1-/- mice showed increasing angiotensin II receptor type 1, monocyte chemotactic protein-1 and interlukin-6 expression, structural damage of endothelial and smooth muscle cells, along with impaired endothelium-dependent relaxation. Hypertension in Plin1-/- mice might occur as a deleterious consequence of PVAT dysfunction. This finding provides the direct evidence that links dysfunctional PVAT to vascular dysfunction and hypertension, particularly in pathophysiological states. This hypertensive mouse model might mimic and explain the hypertension occurring in patients with adipose tissue dysfunction, particularly with Plin1 mutations. PMID:26521150

  7. Stability of immobilized candida sp. 99-125 Lipase for biodiesel production

    Lu, J. [Beijing Bioprocess Key Laboratory, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing (China); Bioengineering Department, Zhengzhou University, Zhengzhou (China); Deng, L.; Nie, K.; Wang, F.; Tan, T. [Beijing Bioprocess Key Laboratory, College of Life Science and Technology, Beijing University of Chemical Technology, Beijing (China)

    2012-12-15

    The stability of the immobilized lipase from Candida sp. 99-125 during biodiesel production was investigated. The lipase was separately incubated in the presence of various reaction components such as soybean oil, oleic acid methyl ester, n-hexane, water, methanol, and glycerol, or the lipase was stored at 60, 80, 100 and 120 C. Thereafter the residual lipase activity was determined by methanolysis reaction. The results showed that the lipase was rather stable in the reaction media, except for methanol and glycerol. The stability study performed in a reciprocal shaker indicated that enzyme desorption from the immobilized lipase mainly contributed to the lipase inactivation in the water system. So the methanol and glycerol contents should be controlled more precisely to avoid lipase inactivation, and the immobilization method should be improved with regard to lipase desorption. (Copyright copyright 2012 WILEY-VCH Verlag GmbH and Co. KGaA, Weinheim)

  8. Immobilization of Yarrowia lipolytica Lipase on Macroporous Resin Using Different Methods: Characterization of the Biocatalysts in Hydrolysis Reaction

    Jingjing Sun

    2015-01-01

    Full Text Available To improve the reusability and organic solvent tolerance of microbial lipase and expand the application of lipase (hydrolysis, esterification, and transesterification, we immobilized marine microbial lipase using different methods and determined the properties of immobilized lipases. Considering the activity and cost of immobilized lipase, the concentration of lipase was fixed at 2 mg/mL. The optimal temperature of immobilized lipases was 40°C and 5°C higher than free lipase. The activities of immobilized lipases were much higher than free lipase at alkaline pH (more than 50% at pH 12. The free lipase lost most activity (35.3% and immobilized lipases retained more than 46.4% of their initial activity after 3 h heat treatment at 70°C. At alkaline pH, immobilized lipases were more stable than free lipase (more than 60% residue activity at pH 11 for 3 h. Immobilized lipases retained 80% of their activity after 5 cycles and increased enzyme activity (more than 108.7% after 3 h treatment in tert-butanol. Immobilization of lipase which improved reusability of lipase and provided a chance to expand the application of marine microbial lipase in organic system expanded the application range of lipase to catalyze hydrolysis and esterification in harsh condition.

  9. JTT-130, a microsomal triglyceride transfer protein (MTP inhibitor lowers plasma triglycerides and LDL cholesterol concentrations without increasing hepatic triglycerides in guinea pigs

    Shrestha Sudeep

    2005-09-01

    Full Text Available Abstract Background Microsomal transfer protein inhibitors (MTPi have the potential to be used as a drug to lower plasma lipids, mainly plasma triglycerides (TG. However, studies with animal models have indicated that MTPi treatment results in the accumulation of hepatic TG. The purpose of this study was to evaluate whether JTT-130, a unique MTPi, targeted to the intestine, would effectively reduce plasma lipids without inducing a fatty liver. Methods Male guinea pigs (n = 10 per group were used for this experiment. Initially all guinea pigs were fed a hypercholesterolemic diet containing 0.08 g/100 g dietary cholesterol for 3 wk. After this period, animals were randomly assigned to diets containing 0 (control, 0.0005 or 0.0015 g/100 g of MTPi for 4 wk. A diet containing 0.05 g/100 g of atorvastatin, an HMG-CoA reductase inhibitor was used as the positive control. At the end of the 7th week, guinea pigs were sacrificed to assess drug effects on plasma and hepatic lipids, composition of LDL and VLDL, hepatic cholesterol and lipoprotein metabolism. Results Plasma LDL cholesterol and TG were 25 and 30% lower in guinea pigs treated with MTPi compared to controls (P Conclusion These results suggest that JTT-130 could have potential clinical applications due to its plasma lipid lowering effects with no alterations in hepatic lipid concentrations.

  10. Medium-chain triglyceride and n-3 polyunsaturated fatty acid-containing emulsions in intravenous nutrition.

    Chan, S; McCowen, K C; Bistrian, B

    1998-03-01

    Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions as a physical mixture have attracted increasing interest for use in parenteral nutrition and may play an important role in the development of structured triglycerides in a future generation of new lipids. Over the past two decades, the clinical use of intravenous emulsion for the nutritional support of hospitalized patients has relied exclusively on long-chain triglycerides providing both a safe, calorically dense alternative to dextrose and a source of essential fatty acids needed for biological membranes and maintenance of the immune function. During the past decade, the development of new triglycerides (medium- and long-chain triglyceride emulsions and structured triglyceride emulsions) for parenteral use have provided useful advances and opportunities to enhance nutritional and metabolic support. Medium-chain triglycerides and n-3 polyunsaturated fatty acid emulsions possess unique physical, chemical, and metabolic properties that make them theoretically advantageous over the conventional long-chain triglycerides. The physical mixture of medium- and long-chain triglycerides have been used clinically in patients with critical illness, liver disease, immunosuppression, pulmonary disease, and in premature infants, with good tolerance and the avoidance of some of the problems encountered with long-chain triglycerides alone. PMID:10565343

  11. Lipase catalyzed synthesis of epoxy-fatty acids

    CHEN, Qian; LI, Zu-Yi

    2000-01-01

    Lipase catalyzed synthesis of epoxy-fatty acidas from unsaturated carboxylic acids was investigated.Under mild conditions unsaturated arboxylic acids were convcveed to peroxide,then the unsaturated peroxycarboxylic acids epoxidised the C=C bond of themselves

  12. Preparation of 3-deacetyl cephalosporins by Aspergillus niger lipase.

    Carrea, G; Corcelli, A; Palmisano, G; Riva, S

    1996-12-20

    Lipase from Aspergillus niger was used for the selective hydrolysis of the 3-O-acetate of cephalosporin C to give an intermediate useful for further chemical elaborations. This lipase was purified to homogeneity and its properties compared with previously published data that present some discrepancies. The lipase proved to be very effective in catalyzing 3-O-acetate hydrolysis and versatile toward substitution on the beta-lactamic ring. In fact, as an example, two other cephalosporinic derivatives, cephalotin and cefotaxime, were efficiently deacetylated. The lipase was immobilized on Eupergit C and employed continuously in either a column or a batch reactor for 2 months without appreciable loss of activity. (c) 1996 John Wiley & Sons, Inc. PMID:18629943

  13. Normal lipase drug-induced pancreatitis: a novel finding.

    Shafqet, Muhammad A; Brown, Teresa V; Sharma, Ranita

    2015-03-01

    Acute pancreatitis (AP) in the setting of a normal serum amylase has been previously reported in the literature. Serum lipase on the other hand has a negative predictive value approaching 100% and therefore is an excellent test to rule out AP in the emergency department. The occurrence of AP with a normal lipase is extremely rare and has never been reported in the setting of drug-induced pancreatitis. Thiazide diuretics have been implicated as a cause of pancreatic injury via a number of proposed mechanisms. However, all such cases have been in the setting of elevated serum amylase or lipase. We report the first case of radiographically proven hydrochlorothiazide-induced pancreatitis with a normal lipase. PMID:25227976

  14. Lipase Activity among Bacteria Isolated from Amazonian Soils.

    Willerding, André Luis; de Oliveira, Luiz Antonio; Moreira, Francisco Wesen; Germano, Mariana Gomes; Chagas, Aloísio Freitas

    2011-01-01

    The objective of this study was to select lipase-producing bacteria collected from different counties of the Amazon region. Of the 440 bacteria strains, 181 were selected for the lipase assay in qualitative tests at Petri dishes, being 75 (41%) lipase positive. The enzymatic index was determined during fifteen days at different temperatures (30°, 35°, 40°, and 45°C). The highest lipase activity was observed within 72 hours at 30°C. Twelve bacteria strains presented an index equal to or greater than the standard used like reference, demonstrating the potential of microbial resource. After the bioassay in Petri dishes, the selected bacteria strains were analyzed in quantitative tests on p-nitrophenyl palmitate (p-NPP). A group of the strains was selected for other phases of study with the use in oleaginous substrates of the Amazonian flora, aiming for the application in processes like oil biotransformation. PMID:22007294

  15. Lipase Activity among Bacteria Isolated from Amazonian Soils

    André Luis Willerding

    2011-01-01

    Full Text Available The objective of this study was to select lipase-producing bacteria collected from different counties of the Amazon region. Of the 440 bacteria strains, 181 were selected for the lipase assay in qualitative tests at Petri dishes, being 75 (41% lipase positive. The enzymatic index was determined during fifteen days at different temperatures (30°, 35°, 40°, and 45°C. The highest lipase activity was observed within 72 hours at 30°C. Twelve bacteria strains presented an index equal to or greater than the standard used like reference, demonstrating the potential of microbial resource. After the bioassay in Petri dishes, the selected bacteria strains were analyzed in quantitative tests on p-nitrophenyl palmitate (p-NPP. A group of the strains was selected for other phases of study with the use in oleaginous substrates of the Amazonian flora, aiming for the application in processes like oil biotransformation.

  16. Lipase inactivation in wheat germ by gamma irradiation

    An attempt was made to improve the shelf life of wheat germ by optimizing processing conditions involving γ-irradiation. Studies were carried out to investigate the effect of γ-irradiation (0–30 kGy doses) on the chemical composition of wheat germ with respect to variation in moisture, total ash, crude fat, free fatty acid, protein and lipase activity. The results demonstrate that shelf stability of wheat germ was achieved by inactivation of lipase at doses of γ-irradiation greater than 12 kGy. - Highlights: Ø γ-irradiation was found to inactivate Lipase present in Wheat Germ. Ø The treatment did not result in significant changes in Total Ash, Moisture and Protein Content of Wheat Germ. Ø The irradiation at 30 kGy resulted in 31.2 % inactivation of Lipase in Wheat Germ

  17. Inhibition of Gastric Lipase as a Mechanism for Body Weight and Plasma Lipids Reduction in Zucker Rats Fed a Rosemary Extract Rich in Carnosic Acid

    Romo Vaquero, María; Yáñez-Gascón, María-Josefa; García Villalba, Rocío; Larrosa, Mar; Fromentin, Emilie; Ibarra, Alvin; Roller, Marc; Tomás-Barberán, Francisco; Espín de Gea, Juan Carlos; García-Conesa, María-Teresa

    2012-01-01

    Background Rosemary (Rosmarinus officinalis L.) extracts (REs) exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA) and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40%) modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. Methods and Principal Findings RE was administered for 64 days to lean (fa/+) and obese (fa/fa) female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate) was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. Conclusions Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption. PMID:22745826

  18. Inhibition of gastric lipase as a mechanism for body weight and plasma lipids reduction in Zucker rats fed a rosemary extract rich in carnosic acid.

    María Romo Vaquero

    Full Text Available BACKGROUND: Rosemary (Rosmarinus officinalis L. extracts (REs exhibit hepatoprotective, anti-obesity and anti-inflammatory properties and are widely used in the food industry. REs are rich in carnosic acid (CA and carnosol which may be responsible for some of the biological activities of REs. The aim of this study was to investigate whether inhibition of lipase activity in the gut may be a mechanism by which a RE enriched in CA (40% modulates body weight and lipids levels in a rat model of metabolic disorders and obesity. METHODS AND PRINCIPAL FINDINGS: RE was administered for 64 days to lean (fa/+ and obese (fa/fa female Zucker rats and body weight, food intake, feces weight and blood biochemical parameters were monitored throughout the study. Lipase activity (hydrolysis of p-nitrophenylbutyrate was measured in the gastrointestinal tract at the end of the study and the contents of CA, carnosol and methyl carnosate were also determined. Sub-chronic administration of RE moderately reduced body weight gain in both lean and obese animals but did not affect food intake. Serum triglycerides, cholesterol and insulin levels were also markedly decreased in the lean animals supplemented with RE. Importantly, lipase activity was significantly inhibited in the stomach of the RE-supplemented animals where the highest content of intact CA and carnosol was detected. CONCLUSIONS: Our results confirm that long-term administration of RE enriched in CA moderates weight gain and improves the plasma lipids profile, primarily in the lean animals. Our data also suggest that these effects may be caused, at least in part, by a significant inhibition of gastric lipase and subsequent reduction in fat absorption.

  19. The adipose organ at a glance

    Saverio Cinti

    2012-09-01

    Full Text Available The main parenchymal cells of the adipose organ are adipocytes. White adipocytes store energy, whereas brown adipocytes dissipate energy for thermogenesis. These two cell types with opposing functions can both originate from endothelial cells, and co-exist in the multiple fat depots of the adipose organ – a feature that I propose is crucial for this organ’s plasticity. This poster review provides an overview of the adipose organ, describing its anatomy, cytology, physiological function and histopathology in obesity. It also highlights the remarkable plasticity of the adipose organ, explaining theories of adipocyte transdifferentiation during chronic cold exposure, physical exercise or lactation, as well as in obesity. White-to-brown adipocyte transdifferentiation is of particular medical relevance, because animal data indicate that higher amounts of brown adipose tissue are positively associated with resistance to obesity and its co-morbidities, and that ‘browning’ of the adipose organ curbs these disorders.

  20. The Adipose Tissue in Farm Animals

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura;

    2014-01-01

    and immune cells. The scientific interest in adipose tissue is largely based on the worldwide increasing prevalence of obesity in humans; in contrast, obesity is hardly an issue for farmed animals that are fed according to their well-defined needs. Adipose tissue is nevertheless of major importance...... in these animals, as the adipose percentage of the bodyweight is a major determinant for the efficiency of transferring nutrients from feed into food products and thus for the economic value from meat producing animals. In dairy animals, the importance of adipose tissue is based on its function as stromal...... and metabolic disorders. We herein provide a general overview of adipose tissue functions and its importance in farm animals. This review will summarize recent achievements in farm animal adipose tissue proteomics, mainly in cattle and pigs, but also in poultry, i.e. chicken and in farmed fish. Proteomics...

  1. KINETICS OF HYDROLYSIS OF TRIBUTYRIN BY LIPASE

    SULAIMAN AL-ZUHAIR

    2006-06-01

    Full Text Available Kinetics of the enzymatic hydrolysis of tributyrin using lipase has been investigated. The initial rate of reaction was determined experimentally at different substrate concentration by measuring the rate of butyric acid produced. Michaels-Menten kinetic model has been proposed to predict the initial rate of hydrolysis of tributyrin in micro-emulsion system. The kinetic parameters were estimated by fitting the data to the model using three methods, namely, the Lineweaver-Burk, Edie-Hofstee and Hanes methods. The Michaels-Menten model with the constant predicted by Edie-Hofstee and Hanes methods predicted the initial rate of reaction at various substrate concentrations better than the model with the constant predicted Lineweaver-Burk method, especially at high substrate concentrations.

  2. Applications of immobilized Thermomyces lanuginosa lipase in interesterification

    Yang, Tiankui; Fruekilde, Maj-Britt; Xu, Xuebing

    2003-01-01

    new immobilized T. lanuginosa lipase was used to produce HMFS from PPP by interesterification with EE. The optimization of major parameters was conducted with the assistance of RSM. The optimal conditions generated were a substrate molar ratio of 5 (EE/PPP), a lipase load of 20 wt% (on substrates......), and a reaction time of 20 h, with acyl incorporation up to 42%. The model generated significantly represented real relationships between the response (incorporation) and reaction parameters....

  3. Hounsfield unit dynamics of adipose tissue and non-adipose soft tissue in growing pigs

    Mcevoy, Fintan; Madsen, Mads T.; Strathe, Anders Bjerring;

    2008-01-01

    Changes in the Hounsfield Unit value of adipose tissue and of no-adipose soft tissue during growth are poorly documented. This study examines the HU of these tissues in growing pigs.......Changes in the Hounsfield Unit value of adipose tissue and of no-adipose soft tissue during growth are poorly documented. This study examines the HU of these tissues in growing pigs....

  4. Gene expression of the zinc transporter ZIP14 (SLC39a14) is affected by weight loss and metabolic status and associates with PPARγ in human adipose tissue and 3T3-L1 pre-adipocytes

    Juul, Trine Maxel; Smidt, Kamille; Larsen, Agnete;

    2015-01-01

    BACKGROUND: The expansion and function of adipose tissue are important during the development of insulin resistance and inflammation in obesity. Zinc dyshomeostasis is common in obese individuals. In the liver, zinc influx transporter ZIP14, affects proliferation and glucose metabolism but the role...... of clinical importance, including body mass index, triglyceride, and insulin resistance, were inversely correlated with ZIP14. During early adipogensis an up-regulation of ZIP14 gene expression was found. PPARγ gene expression was positively correlated with the ZIP14 gene expression in both adipose...... of ZIP14 in adipose tissue is still unknown. This study investigates ZIP14 gene expression in human adipose tissue before and after weight loss as well as the regulation of ZIP14 during early adipogenesis. METHODS: Fourteen obese individuals were investigated before and after a 10 week weight loss...

  5. Biochemistry of adipose tissue: an endocrine organ

    Coelho, Marisa; Oliveira, Teresa; Fernandes, Rúben

    2013-01-01

    Adipose tissue is no longer considered to be an inert tissue that stores fat. This tissue is capable of expanding to accommodate increased lipids through hypertrophy of existing adipocytes and by initiating differentiation of pre-adipocytes. Adipose tissue metabolism exerts an impact on whole-body metabolism. As an endocrine organ, adipose tissue is responsible for the synthesis and secretion of several hormones. These are active in a range of processes, such as control of n...

  6. Adipose Inflammation, Insulin Resistance, and Cardiovascular Disease

    Shah, Arti; Mehta, Nehal; Reilly, Muredach P.

    2008-01-01

    Adiposity-associated inflammation and insulin resistance are strongly implicated in the development of type 2 diabetes and atherosclerotic cardiovascular disease. This article reviews the mechanisms of adipose inflammation, because these may represent therapeutic targets for insulin resistance and for prevention of metabolic and cardiovascular consequences of obesity. The initial insult in adipose inflammation and insulin resistance, mediated by macrophage recruitment and endogenous ligand ac...

  7. Immobilization of Candida cylindracea lipase on PVC, chitin and agarose

    Chang, R.C.; Shaw, J.F.

    1987-01-01

    Candida cylindracea lipase was covalently coupled to PVC, chitin and agarose, which are abundant in Taiwan by several different methods. The agarose-dodecylene-diamine-glutaraldehyde (A-DDA-GA) system showed the highest relative loading enzyme activity, 118 mg soluble lipase per gram support. The chitosan-carbodiimide glutaraldehyde (CN-EDC-GA) systems immobilized 67 mg soluble lipase per gram support. The optimal pH of immobilized lipase was 8.5, which was one pH unit higher than that of soluble lipase. The optimal temperatures were in the range between 52-64/sup 0/C. The CN-EDC-GA system was the highest (64/sup 0/C), which was 27/sup 0/C higher than soluble lipase. The CH-EDC-GA system also had the best thermal stability (the half life at 55/sup 0/C was 29 h.) and operational stability at higher temperature (the half life at 40/sup 0/C was 495 h). However, the PVC-ethylenediamine-GA system appeared to have the best stability at lower temperature, the projected half life at 20/sup 0/C from Arrhenius plot was 31,802 h.

  8. The role of active brown adipose tissue in human metabolism

    Ozguven, Salih; Turoglu, H.T. [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Ones, Tunc [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Nuclear Medicine, Istanbul (Turkey); Kozyatagi/Kadikoy, Istanbul (Turkey); Yilmaz, Yusuf; Imeryuz, Nese [S.B. Marmara Universitesi Pendik Egitim ve Arastirma Hastanesi, Department of Internal Medicine, Division of Gastroenterology, Istanbul (Turkey)

    2016-02-15

    The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing {sup 18}F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the {sup 18}F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

  9. The role of active brown adipose tissue in human metabolism

    The presence of activated brown adipose tissue (ABAT) has been associated with a reduced risk of obesity in adults. We aimed to investigate whether the presence of ABAT in patients undergoing 18F-FDG PET/CT examinations was related to blood lipid profiles, liver function, and the prevalence of non-alcoholic fatty liver disease (NAFLD). We retrospectively and prospectively analysed the 18F-FDG PET/CT scans from 5,907 consecutive patients who were referred to the Nuclear Medicine Department of the Marmara University School of Medicine from outpatient oncology clinics between July 2008 and June 2014 for a variety of diagnostic reasons. Attenuation coefficients for the liver and spleen were determined for at least five different areas. Blood samples were obtained before PET/CT to assess the blood lipid profiles and liver function. A total of 25 of the 5,907 screened individuals fulfilling the inclusion criteria for the study demonstrated brown fat tissue uptake [ABAT(+) subjects]. After adjustment for potential confounders, 75 individuals without evidence of ABAT on PET [ABAT(-) subjects] were enrolled for comparison purposes. The ABAT(+) group had lower total cholesterol, low-density lipoprotein cholesterol, alanine aminotransferase, and aspartate transaminase levels (p < 0.01), whereas we found no significant differences in the serum triglyceride and high-density lipoprotein cholesterol levels between the two groups. The prevalence of NAFLD was significantly lower in ABAT(+) than in ABAT(-) subjects (p < 0.01). Our study showed that the presence of ABAT in adults had a positive effect on their blood lipid profiles and liver function and was associated with reduced prevalence of NAFLD. Thus, our data suggest that activating brown adipose tissue may be a potential target for preventing and treating dyslipidaemia and NAFLD. (orig.)

  10. The lipoprotein lipase gene in combined hyperlipidemia: evidence of a protective allele depletion

    Malloy Mary J

    2006-07-01

    Full Text Available Abstract Background Lipoprotein Lipase (LPL, a key enzyme in lipid metabolism, catalyzes the hydrolysis of triglycerides (TG from TG-rich lipoproteins, and serves a bridging function that enhances the cellular uptake of lipoproteins. Abnormalities in LPL function are associated with pathophysiological conditions, including familial combined hyperlipidemia (FCH. Whereas two LPL susceptibility alleles were found to co-segregate in a few FCH kindred, a role for common, protective alleles remains unexplored. The LPL Ser447Stop (S447X allele is associated with anti-atherogenic lipid profiles and a modest reduction in risk for coronary disease. We hypothesize that significant depletion of the 447X allele exists in combined hyperlipidemia cases versus controls. A case-control design was employed. The polymorphism was assessed by restriction assay in 212 cases and 161 controls. Genotypic, allelic, and phenotypic associations were examined. Results We found evidence of significant allelic (447Xcontrol: 0.130 vs. 447Xcase: 0.031, χ2 = 29.085; 1df; p 2 = 26.09; 1df; p Conclusion These findings suggest a role for the S447X polymorphism in combined hyperlipidemia and demonstrate the importance of evaluating both susceptibility and protective genetic risk factors.

  11. Lysosomal acid lipase deficiency: diagnosis and treatment of Wolman and Cholesteryl Ester Storage Diseases.

    Porto, Anthony F

    2014-09-01

    Lysosomal acid lipase (LAL) is responsible for the hydrolysis of cholesterol esters and triglycerides. LAL is coded by the LIPA gene on chromosome 10q23.31. Its deficiency leads to two autosomal recessive disorders, Wolman disease (WD) and Cholesteryl Ester Storage Disease (CESD). WD has an estimated incidence of 1 in 500,000 live births and is the result of a complete loss of LAL and presents in infancy with vomiting, diarrhea, poor weight gain and hepatomegaly subsequently leading to death. CESD is the result of partial loss of LAL and its presentation is more variable. Patients may be asymptomatic or present with nonspecific gastrointestinal symptoms, hepatomegaly, elevated transaminases and dystipidemia which may be confused with the diagnosis of Non-alcoholic Fatty Liver Disease. CESD is currently underdiagnosed and has an estimated prevalence as high as I in 40,000 individuals. Radiologic findings in WD is calcification of the adrenal glands. Hepatomegaly is noted on CT scan in both WD and CESD. MRI may demonstrate accumulation of cholesterol esters and may be useful to study effects of potential medical therapies. The diagnosis of WD and CESD is based on LIPA gene sequencing and the measurement of LAL levels in peripheral blood leukocytes. Treatment of LAL deficiency is currently limited to control of cholesterol levels and to prevent premature atherosclerosis. Use of enzyme replacement therapy with recombinant human LAL in short-term studies has shown to be safe and effective. PMID:25345094

  12. SINGLE NUCLEOTIDE POLYMORPHISMS OF LIPOPROTEIN LIPASE GENE AND ITS ASSOCIATION WITH MARBLING QUALITY IN LOCAL SHEEPS

    H. Hidayati

    2015-09-01

    Full Text Available Lipoprotein lipase (LPL is a key enzyme that plays in metabolism and transport lipoprotein andtherefore has an influence on blood triglyceride levels. LPL controls triacylglycerol partitioning betweenadipose tissue and muscle that increases fat storage or provides energy in the form of fatty acids formuscle growth. The research was aimed to explore Single Nucleotide Polymorphisms of LPL gene andto associate SNP with marbling quality. A total of 66 genomic DNAs consisted of sumatera thin-tail edsheep (50 heads and garut sheep (16 heads were used in this study. Polymerase Chain Reaction wasused to amplify genomic DNA and direct sequencing method was to identify polymorphism sequences.The sequences were analyzed with Bio Edit and MEGA 5.2. The BLAST sequence was obtained fromgene bank X.68308.1. The association between the genotype and marbling quality was analyze by oneway ANOVA and further between mean differences were tested using least sgnificant difference. Theresults showed that 3 novel SNPs i.e. insertion g.26>C; insertion g.27> G and c.192T>C on garut sheepand a SNP insertion g.26>C/G on sumatera thin-tail ed sheep. The diversity of LPL gene at c.192T>Cwas associated with heneicosanoic acid, whereas TT genotype (0.04% was higher than CC (0.03% andCT (0.02%.

  13. Does Lysosomial Acid Lipase Reduction Play a Role in Adult Non-Alcoholic Fatty Liver Disease?

    Francesco Baratta

    2015-11-01

    Full Text Available Lysosomal Acid Lipase (LAL is a key enzyme involved in lipid metabolism, responsible for hydrolysing the cholesteryl esters and triglycerides. Wolman Disease represents the early onset phenotype of LAL deficiency rapidly leading to death. Cholesterol Ester Storage Disease is a late onset phenotype that occurs with fatty liver, elevated aminotransferase levels, hepatomegaly and dyslipidaemia, the latter characterized by elevated LDL-C and low HDL-C. The natural history and the clinical manifestations of the LAL deficiency in adults are not well defined, and the diagnosis is often incidental. LAL deficiency has been suggested as an under-recognized cause of dyslipidaemia and fatty liver. Therefore, LAL activity may be reduced also in non-obese patients presenting non-alcoholic fatty liver disease (NAFLD, unexplained persistently elevated liver transaminases or with elevation in LDL cholesterol. In these patients, it could be indicated to test LAL activity. So far, very few studies have been performed to assess LAL activity in representative samples of normal subjects or patients with NAFLD. Moreover, no large study has been carried out in adult subjects with NAFLD or cryptogenic cirrhosis.

  14. Common variants associated with plasma triglycerides and risk for coronary artery disease

    Do, R.; Willer, C. J.; Schmidt, E. M.;

    2013-01-01

    Triglycerides are transported in plasma by specific triglyceride-rich lipoproteins; in epidemiological studies, increased triglyceride levels correlate with higher risk for coronary artery disease (CAD). However, it is unclear whether this association reflects causal processes. We used 185 common...... both traits are factors in determining CAD risk. Second, we consider loci with only a strong association with triglycerides and show that these loci are also associated with CAD. Finally, in a model accounting for effects on LDL-C and/or high-density lipoprotein cholesterol (HDL-C) levels, the strength...... of a polymorphism's effect on triglyceride levels is correlated with the magnitude of its effect on CAD risk. These results suggest that triglyceride-rich lipoproteins causally influence risk for CAD....

  15. Triglyceride kinetics in fasted and fed E. coli septic rats

    Lanza-Jacoby, S.; Tabares, A. (Jefferson Medical Coll., Philadelphia, PA (United States))

    1990-02-26

    The mechanism for the development of hypertriglyceridemia during gram-negative sepsis was studies by examining the liver production and clearance of very-low-density lipoprotein (VLDL) triglyceride (TG). To assess the liver output and peripheral clearance the kinetics of VLDL-TG were determined by a constant intravenous infusion of (2-{sup 3}H) glycerol-labeled VLDL in fasted control, fasted E. coli-treated, fed control, and fed E.coli-treated rats. Lewis inbred rats, 275-300 g, were made septic with 8 {times} 10{sup 7} live E.coli colonies per 100 g body weight. Twenty-four hours following E.coli injection serum TG of fasted E.coli-treated rats was elevated by 170% which was attributed to a 67% decrease in the clearance rate of VLDL-TG in fasted E.coli-treated rats compared with their fasted controls. The secretion of VLDL-TG declined by 31% in the livers of the fasted E.coli-treated rats which was accompanied by a 2-fold increase in the composition of liver TG. In a second series of experiments control and E.coli-treated rats were fed intragastrically (IG) a balanced solution containing glucose plus fat as the sources of nonprotein calories. Serum TG were 26% lower in the fed E.coli-treated rats because the clearance rate increased by 86%. The secretion of TG in the fed septic rats increased by 40% but this difference was not significant. In the septic rat the ability to clear triglycerides from the plasma depends upon the nutritional state.

  16. Acquisition of Triacylglycerol Transfer Activity by Microsomal Triglyceride Transfer Protein During Evolution

    Rava, Paul; Hussain, M. Mahmood

    2007-01-01

    Microsomal triglyceride transfer protein (MTP) is essential for the assembly of neutral lipid rich apolipoprotein B (apoB)-lipoproteins. Previously we reported that the Drosophila MTP transfers phospholipids but does not transfer triglycerides. In contrast, human MTP transfers both lipids. To explore the acquisition of triglyceride transfer activity by MTP, we evaluated amino acid sequences, protein structures, as well as the biochemical and cellular properties of various MTP orthologs obtain...

  17. Inflammation and adipose tissue: effects of progressive load training in rats

    Oyama Lila M

    2010-10-01

    Full Text Available Abstract Introduction Cytokines (IL-6, IL-10 and TNF-α are increased after exhaustive exercise in the rat retroperitoneal (RPAT and mesenteric adipose tissue (MEAT pads. On the other hand, these cytokines show decreased expression in these depots in response to a chronic exercise protocol. However, the effect of exercise with overload combined with a short recovery period on pro- and anti-inflammatory cytokine expression is unknown. In the present study, we investigated the regulation of cytokine production in the adipose tissue of rats after an overtraining-inducing exercise protocol. Methods Male Wistar rats were divided into four groups: Control (C, Trained (Tr, Overtrained (OT and recovered overtrained (R. Cytokines (IL-6, TNF-α and IL-10 levels and Toll Like Receptor 4 (TLR4, Nuclear Factor kBp65 (NF-kBp65, Hormone Sensitive Lipase (HSL and, Perilipin protein expression were assessed in the adipose tissue. Furthermore, we analysed plasma lipid profile, insulin, testosterone, corticosterone and endotoxin levels, and liver triacylglycerol, cytokine content, as well as apolipoprotein B (apoB and TLR4 expression in the liver. Results OT and R groups exhibited reduced performance accompanied by lower testosterone and increased corticosterone and endotoxin levels when compared with the control and trained groups. IL-6 and IL-10 protein levels were increased in the adipose tissue of the group allowed to recover, in comparison with all the other studied groups. TLR-4 and NF-kBp65 were increased in this same group when compared with both control and trained groups. The protein expression of HSL was increased and that of Perilipin, decreased in the adipose in R in relation to the control. In addition, we found increased liver and serum TAG, along with reduced apoB protein expression and IL-6 and IL-10 levels in the of R in relation to the control and trained groups. Conclusion In conclusion, we have shown that increases in pro

  18. Soy Isoflavones in Nutritionally Relevant Amounts Have Varied Nutrigenomic Effects on Adipose Tissue

    Elena Giordano

    2015-01-01

    Full Text Available Soy consumption has been suggested to afford protection from cardiovascular disease (CVD. Indeed, accumulated albeit controversial evidence suggests that daily consumption of ≥25 g of soy protein with its associated phytochemicals intact can improve lipid profiles in hypercholesterolemic humans. However, the belief that soy foods and supplements positively impact human health has become increasingly controversial among the general public because of the reported estrogenic activities of soy isoflavones. In this study, we investigated the nutrigenomic actions of soy isoflavones (in nutritionally-relevant amounts with a specific focus on the adipose tissue, due to its pivotal role in cardiometabolism. Young C57BL/6 mice were maintained for eight weeks under two different diet regimes: (1 purified control diet; or (2 purified control diet supplemented with 0.45 g% soybean dry purified extract (a genistein/daidzein mix. Soy isoflavones increased plasma total cholesterol concentrations and decreased triglyceride ones. Circulating leptin levels was also increased by soy consumption. Differentially expressed genes in adipose tissue were classified according to their role(s in cellular or metabolic pathways. Our data show that soy isoflavones, administered in nutritionally-relevant amounts, have diverse nutrigenomic effects on adipose tissue. Taking into account the moderate average exposure to such molecules, their impact on cardiovascular health needs to be further investigated to resolve the issue of whether soy consumption does indeed increase or decrease cardiovascular risk.

  19. Heritability of phenotypes associated with glucose homeostasis and adiposity in a rural area of Brazil.

    Pena, Geórgia G; Dutra, Míriam Santos; Gazzinelli, Andrea; Corrêa-Oliveira, Rodrigo; Velasquez-Melendez, Gustavo

    2014-01-01

    We aimed to estimate the heritability and genetic correlation between glucose homeostasis and adiposity traits in a population in a rural community in Brazil. The Jequitinhonha Community Family Study cohort consists of subjects aged ≥18 years residing in rural areas in Brazil. The data on the following traits were assembled for 280 individuals (51.7% women): body mass index (BMI), body fat percentage, waist and mid-upper arm circumferences, triceps skinfold, conicity index, insulin, glucose, high-density lipoprotein cholesterol (HDLc), triglycerides and C-reactive protein. Extended pedigrees were constructed up to the third generation of individuals using the data management software PEDSYS. The heritability and genetic correlations were estimated using a variance component method. The age- and sex-adjusted heritability values estimated for insulin (h(2) = 52%), glucose (h(2) = 51%), HDLc (h(2) = 58%), and waist circumference (WC; h(2) = 49%) were high. Significantly adjusted genetic correlations were observed between insulin paired with each of the following phenotypes; (BMI; ρg = 0.48), WC (ρg = 0.47) and HDLc (ρg = -0.47). The homeostasis model assessment of insulin resistance (HOMA-IR) was genetically correlated with BMI (ρg = 0.53) and HDLc (ρg = -0.58). The adjusted genetic correlations between traits were consistently higher compared with the environmental correlations. In conclusion, glucose metabolism and adiposity traits are highly heritable and share common genetic effects with body adiposity traits. PMID:24359477

  20. Potencial de biocatálise enantiosseletiva de lipases microbianas Potential of enantioselective biocatalysis by microbial lipases

    Patrícia de O. Carvalho

    2005-08-01

    Full Text Available Microbial lipases have a great potential for commercial applications due to their stability, selectivity and broad substrate specificity because many non-natural acids, alcohols or amines can be used as the substrate. Three microbial lipases isolated from Brazilian soil samples (Aspergillus niger; Geotrichum candidum; Penicillium solitum were compared in terms of their stability and as biocatalysts in the enantioselective esterification using racemic substrates in organic medium. The lipase from Aspergillus niger showed the highest activity (18.2 U/mL and was highly thermostable, retaining 90% and 60% activity at 50 ºC and 60 ºC after 1 hour, respectively. In organic medium, this lipase provided the best results in terms of enantiomeric excess of the (S-active acid (ee = 6.1% and conversion value (c = 20% in the esterification of (R,S-ibuprofen with 1-propanol in isooctane. The esterification reaction of the racemic mixture of (R,S-2-octanol with decanoic acid proceeded with high enantioselectivity when lipase from Aspergillus niger (E = 13.2 and commercial lipase from Candida antarctica (E = 20 were employed.