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Sample records for adipose tissue treatment

  1. Benefits of healthy adipose tissue in the treatment of diabetes.

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    Gunawardana, Subhadra C

    2014-08-15

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin. Insulin deficiency is either absolute due to destruction or failure of pancreatic β cells, or relative due to decreased sensitivity of peripheral tissues to insulin. The primary lesion being related to insulin, treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin. These therapies have their own limitations and complications, some of which can be life-threatening. For example, exogenous insulin administration can lead to fatal hypoglycemic episodes; islet/pancreas transplantation requires life-long immunosuppressive therapy; and anti-diabetic drugs have dangerous side effects including edema, heart failure and lactic acidosis. Thus the need remains for better safer long term treatments for diabetes. The ultimate goal in treating diabetes is to re-establish glucose homeostasis, preferably through endogenously generated hormones. Recent studies increasingly show that extra-pancreatic hormones, particularly those arising from adipose tissue, can compensate for insulin, or entirely replace the function of insulin under appropriate circumstances. Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism. While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines, healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties, which can complement and/or compensate for the function of insulin. Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes, and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin. Although specific adipokines may correct diabetes, administration of individual adipokines still carries risks similar to those of insulin monotherapy. Thus a

  2. Adipose tissue fibrosis

    Institute of Scientific and Technical Information of China (English)

    2015-01-01

    The increasing prevalence of obesity causes a majorinterest in white adipose tissue biology. Adipose tissuecells are surrounded by extracellular matrix proteinswhose composition and remodeling is of crucial importancefor cell function. The expansion of adipose tissue inobesity is linked to an inappropriate supply with oxygenand hypoxia development. Subsequent activation ofhypoxia inducible factor 1 (HIF-1) inhibits preadipocytedifferentiation and initiates adipose tissue fibrosis. Therebyadipose tissue growth is limited and excess triglyceridesare stored in ectopic tissues. Stressed adipocytes andhypoxia contribute to immune cell immigration andactivation which further aggravates adipose tissuefibrosis. There is substantial evidence that adipose tissuefibrosis is linked to metabolic dysfunction,both in rodentmodels and in the clinical setting. Peroxisome proliferatoractivated receptor gamma agonists and adiponectin bothreduce adipose tissue fibrosis, inflammation and insulinresistance. Current knowledge suggests that antifibroticdrugs, increasing adipose tissue oxygen supply or HIF-1antagonists will improve adipose tissue function andthereby ameliorate metabolic diseases.

  3. Short-term oleoyl-estrone treatment affects capacity to manage lipids in rat adipose tissue

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    Remesar Xavier

    2007-08-01

    Full Text Available Abstract Background Short-term OE (oleoyl-estrone treatment causes significant decreases in rat weight mainly due to adipose tissue loss. The aim of this work was to determine if OE treatment affects the expression of genes that regulate lipid metabolism in white adipose tissue. Results Gene expression in adipose tissue from female treated rats (48 hours was analysed by hybridization to cDNA arrays and levels of specific mRNAs were determined by real-time PCR. Treatment with OE decreased the expression of 232 genes and up-regulated 75 other genes in mesenteric white adipose tissue. The use of real-time PCR validate that, in mesenteric white adipose tissue, mRNA levels for Lipoprotein Lipase (LPL were decreased by 52%, those of Fatty Acid Synthase (FAS by 95%, those of Hormone Sensible Lipase (HSL by 32%, those of Acetyl CoA Carboxylase (ACC by 92%, those of Carnitine Palmitoyltransferase 1b (CPT1b by 45%, and those of Fatty Acid Transport Protein 1 (FATP1 and Adipocyte Fatty Acid Binding Protein (FABP4 by 52% and 49%, respectively. Conversely, Tumour Necrosis Factor (TNFα values showed overexpression (198%. Conclusion Short-term treatment with OE affects adipose tissue capacity to extract fatty acids from lipoproteins and to deal with fatty acid transport and metabolism.

  4. Targeting adipose tissue

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    Haas Bodo

    2012-10-01

    Full Text Available Abstract Two different types of adipose tissues can be found in humans enabling them to respond to starvation and cold: white adipose tissue (WAT is generally known and stores excess energy in the form of triacylglycerol (TG, insulates against cold, and serves as a mechanical cushion. Brown adipose tissue (BAT helps newborns to cope with cold. BAT has the capacity to uncouple the mitochondrial respiratory chain, thereby generating heat rather than adenosine triphosphate (ATP. The previously widely held view was that BAT disappears rapidly after birth and is no longer present in adult humans. Using positron emission tomography (PET, however, it was recently shown that metabolically active BAT occurs in defined regions and scattered in WAT of the adult and possibly has an influence on whole-body energy homeostasis. In obese individuals adipose tissue is at the center of metabolic syndrome. Targeting of WAT by thiazolidinediones (TZDs, activators of peroxisome proliferator-activated receptor γ (PPARγ a ‘master’ regulator of fat cell biology, is a current therapy for the treatment of type 2 diabetes. Since its unique capacity to increase energy consumption of the body and to dissipate surplus energy as heat, BAT offers new perspectives as a therapeutic target for the treatment of obesity and associated diseases such as type 2 diabetes and metabolic syndrome. Recent discoveries of new signaling pathways of BAT development give rise to new therapeutic possibilities in order to influence BAT content and activity.

  5. Salsalate treatment improves glycemia without altering adipose tissue in nondiabetic obese hispanics.

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    Alderete, Tanya L; Sattler, Fred R; Richey, Joyce M; Allayee, Hooman; Mittelman, Steven D; Sheng, Xia; Tucci, Jonathan; Gyllenhammer, Lauren E; Grant, Edward G; Goran, Michael I

    2015-03-01

    Salsalate treatment has well-known effects on improving glycemia, and the objective of this study was to examine whether the mechanism of this effect was related to changes in adipose tissue. A randomized double-blind and placebo-controlled trial in obese Hispanics (18-35 years) was conducted. The intervention consisted of 4 g day(-1) of salsalate (n = 11) versus placebo (n = 13) for 4 weeks. Outcome measures included glycemia, adiposity, ectopic fat, and adipose tissue gene expression and inflammation. In those receiving salsalate, plasma fasting glucose decreased by 3.4% (P < 0.01), free fatty acids decreased by 42.5% (P = 0.06), and adiponectin increased by 27.7% (P < 0.01). Salsalate increased insulin AUC by 38% (P = 0.01) and HOMA-B by 47.2% (P < 0.01) while estimates of insulin sensitivity/resistance were unaffected. These metabolic improvements occurred without changes in total, abdominal, visceral, or liver fat. Plasma markers of inflammation/immune activation were unchanged following salsalate. Salsalate had no effects on adipose tissue including adipocyte size, presence of crown-like structures, or gene expression of adipokines, immune cell markers, or cytokines downstream of NF-κB with the exception of downregulation of IL-1β (P < 0.01). Findings suggest that metabolic improvements in response to salsalate occurred without alterations in adiposity, ectopic fat, or adipose tissue gene expression and inflammation. © 2015 The Obesity Society.

  6. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

  7. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically foc

  8. Adipose tissue macrophages

    NARCIS (Netherlands)

    Boutens, Lily; Stienstra, Rinke

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically foc

  9. Multiple effects of a short-term dexamethasone treatment in human skeletal muscle and adipose tissue.

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    Viguerie, Nathalie; Picard, Flora; Hul, Gabby; Roussel, Balbine; Barbe, Pierre; Iacovoni, Jason S; Valle, Carine; Langin, Dominique; Saris, Wim H M

    2012-02-01

    Glucocorticoids are frequently prescribed drugs with important side-effects such as glucose intolerance and tissue remodeling. The goal was to explore the molecular basis of the response of skeletal muscle and adipose tissue during a short-term dexamethasone treatment to better understand the induction of side-effects of glucocorticoids on these metabolic tissues. Fifteen healthy male subjects were assigned to a 4-day treatment with dexamethasone at 4 mg/day. The primary outcome measures were changes in gene expression profiling of subcutaneous skeletal muscle and adipose tissue. Urinary cortisol, plasma, and metabolic biochemistry were also assessed. In both tissues the prominent observation was a response to stress and increased inflammatory responses. An upregulation of the serum amyloid A was detected in skeletal muscle, adipose tissue, and plasma, whereas circulating levels of C reactive protein, another acute phase protein, decreased along with a worsened insulin sensitivity index. As tissue-specific features, tissue remodeling was shown in skeletal muscle while the adipose tissue exhibited a decreased energy metabolism. Several limitations might be raised due to the small number of subjects investigated: a possible cross talk with the mineralocorticoid receptor, and a single time point may not identify regulations occurring during longitudinal treatment. In line with the known physiological effect of glucocorticoids the early modulation of stress response genes was observed. An unexpected feature was the upregulation of the inflammatory and immune pathways. The identification of novel impact on two glucocorticoid target tissues provides a molecular basis for the design of more specific glucocorticoids devoid of adverse effects.

  10. [Human brown adipose tissue].

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    Virtanen, Kirsi A; Nuutila, Pirjo

    2015-01-01

    Adult humans have heat-producing and energy-consuming brown adipose tissue in the clavicular region of the neck. There are two types of brown adipose cells, the so-called classic and beige adipose cells. Brown adipose cells produce heat by means of uncoupler protein 1 (UCP1) from fatty acids and sugar. By applying positron emission tomography (PET) measuring the utilization of sugar, the metabolism of brown fat has been shown to multiply in the cold, presumably influencing energy consumption. Active brown fat is most likely present in young adults, persons of normal weight and women, least likely in obese persons.

  11. Investigations of the endocannabinoid system in adipose tissue: effects of obesity/ weight loss and treatment options.

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    Bennetzen, Marianne Faurholt

    2011-04-01

    Obesity is a world wide epidemic; it is becoming more usual to be overweight or obese than to be normal weight. Obesity increases the risk of an extensive range of diseases such as cardiovascular disease, diabetes mellitus type 2, hypertension, depression and some types of cancer. Adipose tissue is more than a storage organ for surplus energy - it is also a setting for complex metabolic processes and adipose tissue releases substances that interact with other parts of the body to influence several systems including food intake and energy metabolism. The endocannabinoid system (ECS) is one of the signalling systems that control feeding behaviour. The ECS is implicated in many functions, such as pain, memory, addiction, inflammation, and feeding, and could be considered a stress recovery system. It also seems to integrate nutrient intake, metabolism and storage maintaining homeostatic balance. The ECS is a recently discovered system, and research indicates hyperactivity in obesity. The aim of this thesis is to elaborate on the relationships of this widespread system and its elements in adipose tissue in obesity. Study I is a 4 weeks rat intervention study to investigate whether weight independent effect of Rimonabant treatment exists. We found that food intake-tolerance development could be circumvented by cyclic administration of Rimonabant and implications of weight independent effects of treatment. Study II is a cross-sectional study to establish the expression of cannabinoid receptor 1 from various adipose tissue depots of lean and obese persons. In this study we conclude, that the subcutaneous adipose tissue express more CBR1 than the visceral depot in lean, but comparable levels in obese. Study III is a 10 weeks human intervention study to asses the effects on the ECS of 10% weight loss. We found reduction in the ECS in obesity that normalised with weight loss. Our results clearly show the presence of all the components of the ECS in human adipose tissue, and

  12. [Adipose tissue hormones].

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    Haluzík, M; Trachta, P; Haluzíková, D

    2010-10-01

    Adipose tissue had been traditionally considered a passive energy storage site without direct influence on energy homeostasis regulation. This view has been principally changed during early nineties by the discovery of hormonal production of adipose tissue. At present, the list of hormonally active substances of adipose tissue includes more than one hundred factors with paracrine or endocrine activity that play an important role in metabolic, food intake a inflammatory regulations and many other processes. Only minority of adipose tissue-derived hormones is produced exclusively in fat. Most of these factors is primarily put out by other tissues and organs. Adipose tissue-derived hormones are produced not only by adipocytes but also by preadipocytes, immunocompetent and endothelial cells and other cell types residing in fat. This paper summarizes current knowledge about endocrine function of adipose tissue with special respect to its changes in obesity. It also describes its possible role in the ethiopathogenesis of insulin resistance, atherosclerosis and other obesity-related pathologies.

  13. The role of adipose tissue and obesity in causing treatment resistance of acute lymphoblastic leukemia

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    Xia eSheng

    2014-06-01

    Full Text Available Obesity is responsible for ~90,000 cancer deaths per year, increasing cancer incidence and impairing its treatment. Obesity has also been shown to impact hematological malignancies, through as yet unknown mechanisms. Adipocytes are present in bone marrow and the microenvironments of many types of cancer, and have been found to promote cancer cell survival. In this review, we explore several ways in which obesity might cause leukemia treatment resistance. Obese patients may be at a treatment disadvantage due to altered pharmacokinetics of chemotherapy and dosage capping based on ideal body weight. The adipose tissue provides fuel to cancer cells in the form of amino acids and free fatty acids. Adipocytes have been shown to cause cancer cells to resist chemotherapy-induced apoptosis. In addition, obese adipose tissue is phenotypically altered, producing a milieu of pro-inflammatory adipokines and cytokines, some of which have been linked to cancer progression. Given the prevalence of obesity, understanding its role and adipose tissue in ALL treatment is necessary for evaluating current treatment regimen and revealing new therapeutic targets.

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

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    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.

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

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    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.

  16. Secretory function of adipose tissue.

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    Kuryszko, J; Sławuta, P; Sapikowski, G

    2016-01-01

    inflammatory condition, which favours the development of insulin resistance and Type 2 diabetes. Obesity is a systemic illness caused by energy transformation homeostasis disorder which results in an increase in the amount of body fat mass. It effects approximately 40% of dogs and 20% of cats. Illnesses which accompany obesity result, to a great extent, from the secretive role of adipose tissue, which is still little known, which should be included when planning treatment of an obese animal.

  17. Adipose Tissue Metabolism During Hypobaria

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    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.

  18. Foraging at wastewater treatment works affects brown adipose tissue fatty acid profiles in banana bats.

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    Hill, Kate; van Aswegen, Sunet; Schoeman, M Corrie; Claassens, Sarina; Jansen van Rensburg, Peet; Naidoo, Samantha; Vosloo, Dalene

    2016-01-06

    In this study we tested the hypothesis that the decrease in habitat quality at wastewater treatment works (WWTW), such as limited prey diversity and exposure to the toxic cocktail of pollutants, affect fatty acid profiles of interscapular brown adipose tissue (iBrAT) in bats. Further, the antioxidant capacity of oxidative tissues such as pectoral and cardiac muscle may not be adequate to protect those tissues against reactive molecules resulting from polyunsaturated fatty acid auto-oxidation in the WWTW bats. Bats were sampled at two urban WWTW, and two unpolluted reference sites in KwaZulu-Natal, South Africa. Brown adipose tissue (BrAT) mass was lower in WWTW bats than in reference site bats. We found lower levels of saturated phospholipid fatty acids and higher levels of mono- and polyunsaturated fatty acids in WWTW bats than in reference site bats, while C18 desaturation and n-6 to n-3 ratios were higher in the WWTW bats. This was not associated with high lipid peroxidation levels in pectoral and cardiac muscle. Combined, these results indicate that WWTW bats rely on iBrAT as an energy source, and opportunistic foraging on abundant, pollutant-tolerant prey may change fatty acid profiles in their tissue, with possible effects on mitochondrial functioning, torpor and energy usage.

  19. Foraging at wastewater treatment works affects brown adipose tissue fatty acid profiles in banana bats

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    Kate Hill

    2016-02-01

    Full Text Available In this study we tested the hypothesis that the decrease in habitat quality at wastewater treatment works (WWTW, such as limited prey diversity and exposure to the toxic cocktail of pollutants, affect fatty acid profiles of interscapular brown adipose tissue (iBrAT in bats. Further, the antioxidant capacity of oxidative tissues such as pectoral and cardiac muscle may not be adequate to protect those tissues against reactive molecules resulting from polyunsaturated fatty acid auto-oxidation in the WWTW bats. Bats were sampled at two urban WWTW, and two unpolluted reference sites in KwaZulu-Natal, South Africa. Brown adipose tissue (BrAT mass was lower in WWTW bats than in reference site bats. We found lower levels of saturated phospholipid fatty acids and higher levels of mono- and polyunsaturated fatty acids in WWTW bats than in reference site bats, while C18 desaturation and n-6 to n-3 ratios were higher in the WWTW bats. This was not associated with high lipid peroxidation levels in pectoral and cardiac muscle. Combined, these results indicate that WWTW bats rely on iBrAT as an energy source, and opportunistic foraging on abundant, pollutant-tolerant prey may change fatty acid profiles in their tissue, with possible effects on mitochondrial functioning, torpor and energy usage.

  20. Subcutaneous adipose tissue classification

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    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

  1. Renin dynamics in adipose tissue: adipose tissue control of local renin concentrations.

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    Fowler, Jason D; Krueth, Stacy B; Bernlohr, David A; Katz, Stephen A

    2009-02-01

    The renin-angiotensin system (RAS) has been implicated in a variety of adipose tissue functions, including tissue growth, differentiation, metabolism, and inflammation. Although expression of all components necessary for a locally derived adipose tissue RAS has been demonstrated within adipose tissue, independence of local adipose RAS component concentrations from corresponding plasma RAS fluctuations has not been addressed. To analyze this, we varied in vivo rat plasma concentrations of two RAS components, renin and angiotensinogen (AGT), to determine the influence of their plasma concentrations on adipose and cardiac tissue levels in both perfused (plasma removed) and nonperfused samples. Variation of plasma RAS components was accomplished by four treatment groups: normal, DOCA salt, bilateral nephrectomy, and losartan. Adipose and cardiac tissue AGT concentrations correlated positively with plasma values. Perfusion of adipose tissue decreased AGT concentrations by 11.1%, indicating that adipose tissue AGT was in equilibrium with plasma. Cardiac tissue renin levels positively correlated with plasma renin concentration for all treatments. In contrast, adipose tissue renin levels did not correlate with plasma renin, with the exception of extremely high plasma renin concentrations achieved in the losartan-treated group. These results suggest that adipose tissue may control its own local renin concentration independently of plasma renin as a potential mechanism for maintaining a functional local adipose RAS.

  2. Steroid biosynthesis in adipose tissue.

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    Li, Jiehan; Papadopoulos, Vassilios; Vihma, Veera

    2015-11-01

    Tissue-specific expression of steroidogenic enzymes allows the modulation of active steroid levels in a local manner. Thus, the measurement of local steroid concentrations, rather than the circulating levels, has been recognized as a more accurate indicator of the steroid action within a specific tissue. Adipose tissue, one of the largest endocrine tissues in the human body, has been established as an important site for steroid storage and metabolism. Locally produced steroids, through the enzymatic conversion from steroid precursors delivered to adipose tissue, have been proven to either functionally regulate adipose tissue metabolism, or quantitatively contribute to the whole body's steroid levels. Most recently, it has been suggested that adipose tissue may contain the steroidogenic machinery necessary for the initiation of steroid biosynthesis de novo from cholesterol. This review summarizes the evidence indicating the presence of the entire steroidogenic apparatus in adipose tissue and discusses the potential roles of local steroid products in modulating adipose tissue activity and other metabolic parameters.

  3. Lipid droplet remodeling and interaction with mitochondria in mouse brown adipose tissue during cold treatment.

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    Yu, Jinhai; Zhang, Shuyan; Cui, Liujuan; Wang, Weiyi; Na, Huimin; Zhu, Xiaotong; Li, Linghai; Xu, Guoheng; Yang, Fuquan; Christian, Mark; Liu, Pingsheng

    2015-05-01

    Brown adipose tissue (BAT) maintains animal body temperature by non-shivering thermogenesis, which is through uncoupling protein 1 (UCP1) that uncouples oxidative phosphorylation and utilizes β-oxidation of fatty acids released from triacylglycerol (TAG) in lipid droplets (LDs). Increasing BAT activity and "browning" other tissues such as white adipose tissue (WAT) can enhance the expenditure of excess stored energy, and in turn reduce prevalence of metabolic diseases. Although many studies have characterized the biology of BAT and brown adipocytes, BAT LDs especially their activation induced by cold exposure remain to be explored. We have isolated LDs from mouse interscapular BAT and characterized the full proteome using mass spectrometry. Both morphological and biochemical experiments showed that the LDs could tightly associate with mitochondria. Under cold treatment mouse BAT started expressing LD structure protein PLIN-2/ADRP and increased expression of PLIN1. Both hormone sensitive lipase (HSL) and adipose TAG lipase (ATGL) were increased in LDs. In addition, isolated BAT LDs showed increased levels of the mitochondrial protein UCP1, and prolonged cold exposure could stimulate BAT mitochondrial cristae biogenesis. These changes were in agreement with the data from transcriptional analysis. Our results provide the BAT LD proteome for the first time and show that BAT LDs facilitate heat production by coupling increasing TAG hydrolysis through recruitment of ATGL and HSL to the organelle and expression of another LD resident protein PLIN2/ADRP, as well as by tightly associating with activated mitochondria. These findings will benefit the study of BAT activation and the interaction between LDs and mitochondria.

  4. The effect of pheochromocytoma treatment on subclinical inflammation and endocrine function of adipose tissue

    National Research Council Canada - National Science Library

    BOSANSKA, L; PETRAK, O; ZELINKA, T; MRAZ, M; WIDIMSKY, Jr, J; HALUZIK, M

    2009-01-01

    The aim of our study was to evaluate the influence of surgical removal of pheochromocytoma on the endocrine function of adipose tissue and subclinical inflammation as measured by circulating C-reactive protein (CRP) levels...

  5. Adipose tissue plasticity from WAT to BAT and in between.

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    Lee, Yun-Hee; Mottillo, Emilio P; Granneman, James G

    2014-03-01

    Adipose tissue plays an essential role in regulating energy balance through its metabolic, cellular and endocrine functions. Adipose tissue has been historically classified into anabolic white adipose tissue and catabolic brown adipose tissue. An explosion of new data, however, points to the remarkable heterogeneity among the cells types that can become adipocytes, as well as the inherent metabolic plasticity of mature cells. These data indicate that targeting cellular and metabolic plasticity of adipose tissue might provide new avenues for treatment of obesity-related diseases. This review will discuss the developmental origins of adipose tissue, the cellular complexity of adipose tissues, and the identification of progenitors that contribute to adipogenesis throughout development. We will touch upon the pathological remodeling of adipose tissue and discuss how our understanding of adipose tissue remodeling can uncover new therapeutic targets. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  6. Improvement of Liquid Fructose-Induced Adipose Tissue Insulin Resistance by Ginger Treatment in Rats Is Associated with Suppression of Adipose Macrophage-Related Proinflammatory Cytokines

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    Jianwei Wang

    2013-01-01

    Full Text Available Adipose tissue insulin resistance (Adipo-IR results in excessive release of free fatty acids from adipose tissue, which plays a key role in the development of “lipotoxicity.” Therefore, amelioration of Adipo-IR may benefit the treatment of other metabolic abnormalities. Here we found that treatment with the alcoholic extract of ginger (50 mg/kg/day, by oral gavage for five weeks attenuated liquid fructose-induced hyperinsulinemia and an increase in the homeostasis model assessment of insulin resistance (HOMA-IR index in rats. More importantly, ginger reversed the increases in the Adipo-IR index and plasma nonesterified fatty acid concentrations during the oral glucose tolerance test assessment. Adipose gene/protein expression profiles revealed that ginger treatment suppressed CD68 and F4/80, two important macrophage accumulation markers. Consistently, the macrophage-associated cytokines tissue necrosis factor alpha and interleukin-6 were also downregulated. In contrast, insulin receptor substrate (IRS-1, but not IRS-2, was upregulated. Moreover, monocyte chemotactic protein (MCP-1 and its receptor chemokine (C-C motif receptor-2 were also suppressed. Thus these results suggest that amelioration of fructose-induced Adipo-IR by ginger treatment in rats is associated with suppression of adipose macrophage-related proinflammatory cytokines.

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

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    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.

  8. Bioengineering Beige Adipose Tissue Therapeutics.

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    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

  9. Adipose tissue lipolysis.

    Science.gov (United States)

    Kolditz, Catherine-Ines; Langin, Dominique

    2010-07-01

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

  10. Pioglitazone treatment reduces adipose tissue inflammation through reduction of mast cell and macrophage number and by improving vascularity.

    Directory of Open Access Journals (Sweden)

    Michael Spencer

    Full Text Available Adipose tissue in insulin resistant subjects contains inflammatory cells and extracellular matrix components. This study examined adipose pathology of insulin resistant subjects who were treated with pioglitazone or fish oil.Adipose biopsies were examined from nine insulin resistant subjects before/after treatment with pioglitazone 45 mg/day for 12 weeks and also from 19 subjects who were treated with fish oil (1,860 mg EPA, 1,500 mg DHA daily. These studies were performed in a clinical research center setting.Pioglitazone treatment increased the cross-sectional area of adipocytes by 18% (p = 0.01, and also increased capillary density without affecting larger vessels. Pioglitazone treatment decreased total adipose macrophage number by 26%, with a 56% decrease in M1 macrophages and an increase in M2 macrophages. Mast cells were more abundant in obese versus lean subjects, and were decreased from 24 to 13 cells/mm(2 (p = 0.02 in patients treated with pioglitazone, but not in subjects treated with FO. Although there were no changes in total collagen protein, pioglitazone increased the amount of elastin protein in adipose by 6-fold.The PPARγ agonist pioglitazone increased adipocyte size yet improved other features of adipose, increasing capillary number and reducing mast cells and inflammatory macrophages. The increase in elastin may better permit adipocyte expansion without triggering cell necrosis and an inflammatory reaction.

  11. WJD 5th Anniversary Special Issues(1): Insulin Benefits of healthy adipose tissue in the treatment of diabetes

    Institute of Scientific and Technical Information of China (English)

    Subhadra; C; Gunawardana

    2014-01-01

    The major malfunction in diabetes mellitus is severe perturbation of glucose homeostasis caused by deficiency of insulin.Insulin deficiency is either absolute due to destruction or failure of pancreaticβcells,or relative due to decreased sensitivity of peripheral tissues to insulin.The primary lesion being related to insulin,treatments for diabetes focus on insulin replacement and/or increasing sensitivity to insulin.These therapies have their own limitations and complications,some of which can be life-threatening.For example,exogenous insulin administration can lead to fatal hypoglycemic episodes;islet/pancreas transplantation requires life-long immunosuppressive therapy;and anti-diabetic drugs have dangerous side effects including edema,heart failure and lactic acidosis.Thus the need remains for better safer long term treatments for diabetes.The ultimate goal in treating diabetes is to re-establish glucose homeostasis,preferably through endogenously generated hormones.Recent studies increasingly show that extra-pancreatic hormones,particularly those arising from adipose tissue,can compensate for insulin,or entirely replace the function of insulin under appropriate circumstances.Adipose tissue is a versatile endocrine organ that secretes a variety of hormones with far-reaching effects on overall metabolism.While unhealthy adipose tissue can exacerbate diabetes through limiting circulation and secreting of pro-inflammatory cytokines,healthy uninflamed adipose tissue secretes beneficial adipokines with hypoglycemic and anti-inflammatory properties,which can complement and/or compensate for the function of insulin.Administration of specific adipokines is known to alleviate both type 1 and 2 diabetes,and leptin mono-therapy is reported to reverse type 1 diabetes independent of insulin.Although specific adipokines may correct diabetes,administration of individual adipokines still carries risks similar to those of insulin monotherapy.Thus a better approach is to

  12. Changes in the before and after thyroxine treatment levels of adipose tissue, leptin, and resistin in subclinical hypothyroid patients.

    Science.gov (United States)

    Akbaba, Gulhan; Berker, Dilek; Isık, Serhat; Tuna, Mazhar Muslum; Koparal, Suha; Vural, Murat; Yılmaz, Fatma Meric; Topcuoglu, Canan; Guler, Serdar

    2016-08-01

    Subclinical hypothyroidism (SH) occurs when serum thyroid stimulating hormone (TSH) concentrations are raised and serum thyroid hormone concentrations are normal. The effect of SH on the proinflammatory adipose cytokine releasing visceral adipose tissue (VAT) is not clear. The aim of this study is to identify the difference between the pre and posttreatment levels of VAT, leptin, and resistin in SH patients. There were 51 SH patients and 43 age- and gender-matched healthy subjects included in the study. Thyroid functions, biochemical tests, leptin, resistin, and visceral and subcutaneous fat measurements were made. The measurements were repeated in the SH group in the third month following L-thyroxin treatment. Initially, high sensitivity C-reactive protein, carotid artery intima-media thickness (mm), leptin, and resistin levels were significantly higher in the SH group compared to the controls, while the other parameters were similar. While no correlation was observed between TSH levels and adipokines, a positive correlation was detected between waist circumference and leptin levels (r = 0.549, p adipose tissue was positively correlated to age, waist circumference, and leptin levels, but negatively correlated to free thyroxin (T4) levels (r = 0.419, p = 0.009; r = 0.794, p leptin, and resistin levels of SH patients following levothyroxine treatment. Conclusion The reduced VAT volume, leptin, and resistin levels in SH patients following treatment may support the idea that TSH affects adipose tissue functions.

  13. Adipose tissue as mesenchymal stem cells source in equine tendinitis treatment

    Directory of Open Access Journals (Sweden)

    Armando de Mattos Carvalho

    2016-12-01

    Full Text Available Tendinitis is an important high-relapse-rate disease, which compromises equine performance and may result in early athletic life end to affected animals. Many therapies have been set to treat equine tendinitis; however, just few result in improved relapse rates, quality of extracellular matrix (ECM and increased biomechanical resistance of the treated tissue. Due to advances in the regenerative medicine, promising results were initially obtained through the implantation of mesenchymal stem cells (MSC derived from the bone marrow in the equine tendon injury. Since then, many studies have been using MSCs from different sources for therapeutic means in equine. The adipose tissue has appeared as feasible MSC source. There are promising results involving equine tendinitis therapy using mesenchymal stem cells from adipose tissue (AdMSCs.

  14. Brown adipose tissue and its therapeutic potential.

    Science.gov (United States)

    Lidell, M E; Betz, M J; Enerbäck, S

    2014-10-01

    Obesity and related diseases are a major cause of human morbidity and mortality and constitute a substantial economic burden for society. Effective treatment regimens are scarce, and new therapeutic targets are needed. Brown adipose tissue, an energy-expending tissue that produces heat, represents a potential therapeutic target. Its presence is associated with low body mass index, low total adipose tissue content and a lower risk of type 2 diabetes mellitus. Knowledge about the development and function of thermogenic adipocytes in brown adipose tissue has increased substantially in the last decade. Important transcriptional regulators have been identified, and hormones able to modulate the thermogenic capacity of the tissue have been recognized. Intriguingly, it is now clear that humans, like rodents, possess two types of thermogenic adipocytes: the classical brown adipocytes found in the interscapular brown adipose organ and the so-called beige adipocytes primarily found in subcutaneous white adipose tissue after adrenergic stimulation. The presence of two distinct types of energy-expending adipocytes in humans is conceptually important because these cells might be stimulated and recruited by different signals, raising the possibility that they might be separate potential targets for therapeutic intervention. In this review, we will discuss important features of the energy-expending brown adipose tissue and highlight those that may serve as potential targets for pharmacological intervention aimed at expanding the tissue and/or enhancing its function to counteract obesity.

  15. Chronic treatment with myo-inositol reduces white adipose tissue accretion and improves insulin sensitivity in female mice.

    Science.gov (United States)

    Croze, Marine L; Vella, Roxane E; Pillon, Nicolas J; Soula, Hédi A; Hadji, Lilas; Guichardant, Michel; Soulage, Christophe O

    2013-02-01

    Type 2 diabetes is a complex disease characterized by a state of insulin resistance in peripheral tissues such as skeletal muscle, adipose tissue or liver. Some inositol isomers have been reported to possess insulin-mimetic activity and to be efficient in lowering blood glucose level. The aim of the present study was to assess in mice the metabolic effects of a chronic treatment with myo-inositol, the most common stereoisomer of inositol. Mice given myo-inositol treatment (0.9 or 1.2 mg g(-1) day(-1), 15 days, orally or intraperitoneally) exhibited an improved glucose tolerance due to a greater insulin sensitivity. Mice treated with myo-inositol exhibited a decreased white adipose tissue accretion (-33%, Padipose tissue deposition was due to a decrease in adipose cell volume (-33%, Pinsulin-stimulated conditions, suggesting a synergistic action of myo-inositol treatment and insulin on proteins of the insulin signalling pathway. Myo-inositol could therefore constitute a viable nutritional strategy for the prevention and/or treatment of insulin resistance and type 2 diabetes. Copyright © 2013 Elsevier Inc. All rights reserved.

  16. Adipose tissue remodeling and obesity

    National Research Council Canada - National Science Library

    Sun, Kai; Kusminski, Christine M; Scherer, Philipp E

    2011-01-01

    To fulfill its role as the major energy-storing tissue, adipose has several unique properties that cannot be seen in any other organ, including an almost unlimited capacity to expand in a non-transformed state...

  17. Obesity-related hypertension: epidemiology, pathophysiology, treatments, and the contribution of perivascular adipose tissue.

    Science.gov (United States)

    Aghamohammadzadeh, Reza; Heagerty, Anthony M

    2012-06-01

    The advent of the obesity epidemic has highlighted the need to re-assess more closely the pathophysiology of obesity-related hypertension with the aim of identifying new therapies. In this article, we review the role of the renin-angiotensin-aldosterone system, sympathetic nervous system, and inflammation in relation to the pathophysiology of this condition. We also discuss the potential role of the perivascular adipose tissue in the context of obesity-related hypertension.

  18. Heat shock proteins: in vivo heat treatments reveal adipose tissue depot-specific effects.

    Science.gov (United States)

    Rogers, Robert S; Beaudoin, Marie-Soleil; Wheatley, Joshua L; Wright, David C; Geiger, Paige C

    2015-01-01

    Heat treatments (HT) and the induction of heat shock proteins (HSPs) improve whole body and skeletal muscle insulin sensitivity while decreasing white adipose tissue (WAT) mass. However, HSPs in WAT have been understudied. The purpose of the present study was to examine patterns of HSP expression in WAT depots, and to examine the effects of a single in vivo HT on WAT metabolism. Male Wistar rats received HT (41°C, 20 min) or sham treatment (37°C), and 24 h later subcutaneous, epididymal, and retroperitoneal WAT depots (SCAT, eWAT, and rpWAT, respectively) were removed for ex vivo experiments and Western blotting. SCAT, eWAT, and rpWAT from a subset of rats were also cultured separately and received a single in vitro HT or sham treatment. HSP72 and HSP25 expression was greatest in more metabolically active WAT depots (i.e., eWAT and rpWAT) compared with the SCAT. Following HT, HSP72 increased in all depots with the greatest induction occurring in the SCAT. In addition, HSP25 increased in the rpWAT and eWAT, while HSP60 increased in the rpWAT only in vivo. Free fatty acid (FFA) release from WAT explants was increased following HT in the rpWAT only, and fatty acid reesterification was decreased in the rpWAT but increased in the SCAT following HT. HT increased insulin responsiveness in eWAT, but not in SCAT or rpWAT. Differences in HSP expression and induction patterns following HT further support the growing body of literature differentiating distinct WAT depots in health and disease.

  19. Preweaning growth hormone treatment ameliorates adipose tissue insulin resistance and inflammation in adult male offspring following maternal undernutrition.

    Science.gov (United States)

    Reynolds, C M; Li, M; Gray, C; Vickers, M H

    2013-08-01

    It is well established that early-life nutritional alterations lead to increased risk of obesity and metabolic disorders in adult life. Although it is clear that obesity gives rise to chronic low-grade inflammation, there is little evidence regarding the role of inflammation in the adipose tissue of undernourished (UN) offspring. GH reduces fat mass and has antiinflammatory properties. The present study examined the effect of maternal UN on adipose inflammation in adult offspring and whether GH treatment during a critical period of developmental plasticity could ameliorate metabolic dysfunction associated with a poor start to life. Sprague Dawley rats were assigned to chow (C) or UN (50% ad libitum; UN) diet throughout gestation. Male C and UN pups received saline (control saline [CS]/UN) or GH (2.5 μg/g/d; control growth hormone [CGH]/undernourished growth hormone [UNGH]) from days 3-21. Postweaning males were further randomized and fed either chow or high-fat diet until day 160. An ex vivo glucose uptake assay demonstrated adipose tissue from UN offspring displayed attenuated insulin-stimulated glucose uptake compared with CS, CGH, and UNGH. This was associated with increased insulin receptor, glucose transporter 4, and insulin receptor substrate 1 gene expression. Furthermore, UN demonstrated enhanced TNFα and IL-1β secretion from adipose explants and stromal vascular fraction cultures accompanied by increased adipose tissue gene expression of several key proinflammatory genes and markers of macrophage infiltration. Overall, UN offspring displayed a more potent immunophenotype, which correlated with decreased insulin sensitivity. Preweaning GH treatment negates these detrimental effects, indicating the potential for reversing metabolic dysfunction in UN adult offspring.

  20. Responses of brown adipose tissue to diet-induced obesity, exercise, dietary restriction and ephedrine treatment.

    Science.gov (United States)

    Slocum, Nikki; Durrant, Jessica R; Bailey, David; Yoon, Lawrence; Jordan, Holly; Barton, Joanna; Brown, Roger H; Clifton, Lisa; Milliken, Tula; Harrington, Wallace; Kimbrough, Carie; Faber, Catherine A; Cariello, Neal; Elangbam, Chandikumar S

    2013-07-01

    Drug-induced weight loss in humans has been associated with undesirable side effects not present in weight loss from lifestyle interventions (caloric restriction or exercise). To investigate the mechanistic differences of weight loss by drug-induced and lifestyle interventions, we examined the gene expression (mRNA) in brown adipose tissue (BAT) and conducted histopathologic assessments in diet-induced obese (DIO) mice given ephedrine (18 mg/kg/day orally), treadmill exercise (10 m/min, 1-h/day), and dietary restriction (DR: 26% dietary restriction) for 7 days. Exercise and DR mice lost more body weight than controls and both ephedrine and exercise reduced percent body fat. All treatments reduced BAT and liver lipid accumulation (i.e., cytoplasmic lipids in brown adipocytes and hepatocytes) and increased oxygen consumption (VO2 ml/kg/h) compared with controls. Mitochondrial biogenesis/function-related genes (TFAM, NRF1 and GABPA) were up-regulated in the BAT of all groups. UCP-1 was up-regulated in exercise and ephedrine groups, whereas MFSD2A was up-regulated in ephedrine and DR groups. PGC-1α up-regulation was observed in exercise and DR groups but not in ephedrine group. In all experimental groups, except for ephedrine, fatty acid transport and metabolism genes were up-regulated, but the magnitude of change was higher in the DR group. PRKAA1 was up-regulated in all groups but not significantly in the ephedrine group. ADRß3 was slightly up-regulated in the DR group only, whereas ESRRA remained unchanged in all groups. Although our data suggest a common pathway of BAT activation elicited by ephedrine treatment, exercise or DR, mRNA changes were indicative of additional nutrient-sensing pathways in exercise and DR.

  1. Adipose tissues and thyroid hormones

    Directory of Open Access Journals (Sweden)

    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

  2. Adipose tissues and thyroid hormones.

    Science.gov (United States)

    Obregon, Maria-Jesus

    2014-01-01

    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 lead to activation of UCP1 in WAT and

  3. Successful application of subcutaneous adipose tissue with fibrin glue in conservative treatment of tracheobronchial rupture.

    Science.gov (United States)

    Tokuishi, Keita; Yamamoto, Satoshi; Anami, Kentaro; Moroga, Toshihiko; Miyawaki, Michiyo; Chujo, Masao; Yamashita, Shin-Ichi; Kawahara, Katsunobu

    2012-11-01

    An 84-year-old woman underwent aortic and mitral valve replacement. After weaning from cardiopulmonary bypass, hemorrhage was observed in the endobronchial tube. The bleeding bronchus was isolated to protect the airway using the blocker cuff of a Univent tube (Fuji Systems Corp, Tokyo, Japan). Computed tomography showed a pulmonary pseudoaneurysm in the left upper lobe. She underwent selective pulmonary angiography and embolization of the pseudoaneurysm. Bronchoscopy revealed a 5-mm bronchial rupture at the left upper lobe bronchus. The laceration was filled with adipose tissue and fibrin glue. Bronchoscopy showed a completely reepithelialized membrane, and she was discharged 38 days postoperatively.

  4. PEDF expression is inhibited by insulin treatment in adipose tissue via suppressing 11β-HSD1.

    Science.gov (United States)

    Zhou, Yinli; Xu, Fen; Deng, Hongrong; Bi, Yan; Sun, Weiping; Zhao, Yi; Chen, Zonglan; Weng, Jianping

    2013-01-01

    Early intensive insulin therapy improves insulin sensitivity in type 2 diabetic patients; while the underlying mechanism remains largely unknown. Pigment epithelium-derived factor (PEDF), an anti-angiogenic factor, is believed to be involved in the pathogenesis of insulin resistance. Here, we hypothesize that PEDF might be down regulated by insulin and then lead to the improved insulin resistance in type 2 diabetic patients during insulin therapy. We addressed this issue by investigating insulin regulation of PEDF expression in diabetic conditions. The results showed that serum PEDF was reduced by 15% in newly diagnosed type 2 diabetic patients after insulin therapy. In adipose tissue of diabetic Sprague-Dawley rats, PEDF expression was associated with TNF-α elevation and it could be decreased both in serum and in adipose tissue by insulin treatment. In adipocytes, PEDF was induced by TNF-α through activation of NF-κB. The response was inhibited by knockdown and enhanced by over expression of NF-κB p65. However, PEDF expression was indirectly, not directly, induced by NF-κB which promoted 11β-hydroxysteroid dehydrogenase 1 (11β-HSD1) expression in adipocytes. 11β-HSD1 is likely to stimulate PEDF expression through production of active form of glucocorticoids as dexamethasone induced PEDF expression in adipose tissue. Insulin inhibited PEDF by down-regulating 11β-HSD1 expression. The results suggest that PEDF activity is induced by inflammation and decreased by insulin through targeting 11β-HSD1/glucocorticoid pathway in adipose tissue of diabetic patients.

  5. Capillary permeability in adipose tissue

    DEFF Research Database (Denmark)

    Paaske, W P; Nielsen, S L

    1976-01-01

    of about 7 ml/100 g-min. This corresponds to a capillary diffusion capacity of 2.0 ml/100 g-min which is half the value reported for vasodilated skeletal muscle having approximately twice as great capillary surface area. Thus, adipose tissue has about the same capillary permeability during slight metabolic...

  6. Glucose transport in adipose tissue

    NARCIS (Netherlands)

    Schoonen, AJM; Wientjes, KJC

    2005-01-01

    Based on the well-known extraction equation and the histology of subcutaneous adipose tissue, transport of glucose from capillary to microdialysis probe is described. Results are evaluated of previous studies by our group and others. Arguments are presented for a simple scheme in which the mean

  7. Hypothalamic control of adipose tissue.

    Science.gov (United States)

    Stefanidis, A; Wiedmann, N M; Adler, E S; Oldfield, B J

    2014-10-01

    A detailed appreciation of the control of adipose tissue whether it be white, brown or brite/beige has never been more important to the development of a framework on which to build therapeutic strategies to combat obesity. This is because 1) the rate of fatty acid release into the circulation from lipolysis in white adipose tissue (WAT) is integrally important to the development of obesity, 2) brown adipose tissue (BAT) has now moved back to center stage with the realization that it is present in adult humans and, in its activated form, is inversely proportional to levels of obesity and 3) the identification and characterization of "brown-like" or brite/beige fat is likely to be one of the most exciting developments in adipose tissue biology in the last decade. Central to all of these developments is the role of the CNS in the control of different fat cell functions and central to CNS control is the integrative capacity of the hypothalamus. In this chapter we will attempt to detail key issues relevant to the structure and function of hypothalamic and downstream control of WAT and BAT and highlight the importance of developing an understanding of the neural input to brite/beige fat cells as a precursor to its recruitment as therapeutic target.

  8. Effects of anabolic steroid treatment associated with physical training in adipose tissue of male Wistar rats

    Directory of Open Access Journals (Sweden)

    Marcela de Paiva Foletto

    2015-06-01

    Full Text Available Anabolic androgenic-steroids (AAS include a broad class of synthetic derivatives of testosterone, being nandrolone decanoate the most widely used in sports environment. The aim of this study was to evaluate the metabolic effects of nandrolone decanoate in sedentary and trained adult male rats. We established four experimental groups: sedentary control, sedentary treated, trained control and trained treated. The training had consisted of running on a treadmill for nine weeks. Treated animals received intramuscular injections of nandrolone decanoate (0.5 mg kg-1 during the last four weeks of physical training. The training time as the drug used were not sufficient to significantly reduce body weight gain, but caused a significative decrease on diameter of adipocytes and in the amount of adipose tissue stored, as well as decreased the plasma levels of glucose and total cholesterol.

  9. Adipose Tissue Redistribution and Ectopic Lipid Deposition in Active Acromegaly and Effects of Surgical Treatment

    Science.gov (United States)

    Reyes-Vidal, Carlos M.; Mojahed, Hamed; Shen, Wei; Jin, Zhezhen; Arias-Mendoza, Fernando; Fernandez, Jean Carlos; Gallagher, Dympna; Bruce, Jeffrey N.; Post, Kalmon D.

    2015-01-01

    Context: GH and IGF-I have important roles in the maintenance of substrate metabolism and body composition. However, when in excess in acromegaly, the lipolytic and insulin antagonistic effects of GH may alter adipose tissue (AT) deposition. Objectives: The purpose of this study was to examine the effect of surgery for acromegaly on AT distribution and ectopic lipid deposition in liver and muscle. Design: This was a prospective study before and up to 2 years after pituitary surgery. Setting: The setting was an academic pituitary center. Patients: Participants were 23 patients with newly diagnosed, untreated acromegaly. Main Outcome Measures: We determined visceral (VAT), subcutaneous (SAT), and intermuscular adipose tissue (IMAT), and skeletal muscle compartments by total-body magnetic resonance imaging, intrahepatic and intramyocellular lipid by proton magnetic resonance spectroscopy, and serum endocrine, metabolic, and cardiovascular risk markers. Results: VAT and SAT masses were lower than predicted in active acromegaly, but increased after surgery in male and female subjects along with lowering of GH, IGF-I, and insulin resistance. VAT and SAT increased to a greater extent in men than in women. Skeletal muscle mass decreased in men. IMAT was higher in active acromegaly and decreased in women after surgery. Intrahepatic lipid increased, but intramyocellular lipid did not change after surgery. Conclusions: Acromegaly may present a unique type of lipodystrophy characterized by reduced storage of AT in central depots and a shift of excess lipid to IMAT. After surgery, this pattern partially reverses, but differentially in men and women. These findings have implications for understanding the role of GH in body composition and metabolic risk in acromegaly and other clinical settings of GH use. PMID:26037515

  10. Adipose tissue, diet and aging.

    Science.gov (United States)

    Zamboni, Mauro; Rossi, Andrea P; Fantin, Francesco; Zamboni, Giulia; Chirumbolo, Salvatore; Zoico, Elena; Mazzali, Gloria

    2014-01-01

    Age related increase in body fat mass, visceral adipose tissue (AT), and ectopic fat deposition are strongly related to worse health conditions in the elderly. Moreover, with aging higher inflammation in adipose tissue may be observed and may contribute to inflammaging. Aging may significantly affect AT function by modifying the profile of adipokines produced by adipose cells, reducing preadipocytes number and their function and increasing AT macrophages infiltration. The initiating events of the inflammatory cascade promoting a greater AT inflammatory profile are not completely understood. Nutrients may determine changes in the amount of body fat, in its distribution as well as in AT function with some nutrients showing a pro-inflammatory effect on AT. Evidences are sparse and quite controversial with only a few studies performed in older subjects. Different dietary patterns are the result of the complex interaction of foods and nutrients, thus more studies are needed to evaluate the association between dietary patterns and changes in adipose tissue structure, distribution and function in the elderly.

  11. Quantification of adipose tissue insulin sensitivity.

    Science.gov (United States)

    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. Copyright © 2016 American Federation for Medical Research.

  12. Importance of changes in adipose tissue insulin resistance to histological response during thiazolidinedione treatment of patients with nonalcoholic steatohepatitis

    National Research Council Canada - National Science Library

    Gastaldelli, Amalia; Harrison, Stephen A; Belfort‐Aguilar, Renata; Hardies, Lou Jean; Balas, Bogdan; Schenker, Steven; Cusi, Kenneth

    2009-01-01

    ...). Because abnormal lipid metabolism/elevated plasma free fatty acids (FFAs) are important to the pathophysiology of NASH, we examined the impact of pioglitazone therapy on adipose tissue insulin resistance (Adipo‐IR...

  13. Adipose tissue and adipocyte dysregulation.

    Science.gov (United States)

    Lafontan, M

    2014-02-01

    Obesity-associated insulin resistance is a complex disorder involving a number of candidate molecules, pathways and transduction systems possessing potential causal actions. Inflammation in adipose tissue (AT) is one mechanism proposed to explain the development of insulin resistance, while identification of factors that lead to or cause AT dysfunction when it reaches its limit of expansion represents an important challenge. Pathological expansion of AT is characterized by changes in its blood flow, and the presence of enlarged and dysfunctional adipocytes that begin an inflammatory campaign of altered adipokine and cytokine secretions. Adipocyte senescence, necrosis and death are associated with increased immune cell and macrophage infiltration of AT in obesity. This can boost inflammation and reinforce fat cell dysfunction and death. In addition, pathological fat mass expansion is also related to limited recruitment of fat cell progenitors able to proliferate and differentiate into healthy small fat cells to compensate for cell death and preserve adipocyte numbers. Limiting vascular development and enhancing fibrotic processes worsen inflammation towards chronic irreversibility. The AT expandability hypothesis states that failure of AT expansion is one of the key factors linking positive energy balance and cardiometabolic risks, not obesity per se. Besides the usual treatment of obesity based on behavioral approaches (specific dietary/nutritional approaches together with increased physical activity), a number of questions remain concerning the possible recovery of metabolic health after inflammation-preventing interventions. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  14. Adipose Tissue Immunity and Cancer

    Directory of Open Access Journals (Sweden)

    Victoria eCatalan

    2013-10-01

    Full Text Available Inflammation and altered immune response are important components of obesity and contribute greatly to the promotion of obesity-related metabolic complications, especially cancer development. Adipose tissue expansion is associated with increased infiltration of various types of immune cells from both the innate and adaptive immune systems. Thus, adipocytes and infiltrating immune cells secrete proinflammatory adipokines and cytokines providing a microenvironment favourable for tumour growth. Accumulation of B and T cells in adipose tissue precedes macrophage infiltration causing a chronic low-grade inflammation. Phenotypic switching towards M1 macrophages and Th1 T cells constitutes an important mechanism described in the obese state correlating with increased tumour growth risk. Other possible synergic mechanisms causing a dysfunctional adipose tissue include fatty acid-induced inflammation, oxidative stress, endoplasmic reticulum stress, and hypoxia. Recent investigations have started to unravel the intricacy of the cross-talk between tumour cell/immune cell/adipocyte. In this sense, future therapies should take into account the combination of anti-inflammatory approaches that target the tumour microenvironment with more sophisticated and selective anti-tumoural drugs.

  15. The endocrine function of adipose tissue

    Directory of Open Access Journals (Sweden)

    Wagner de Jesus Pinto

    2014-09-01

    Full Text Available Currently it is considered the adipose tissue as a dynamic structure involved in many physiological and metabolic processes, produces and releases a variety of active peptides known by the generic name of adipokines that act performing endocrine, paracrine and autocrine. Furthermore, numbers expressed receptors that respond allows the afferent signals from endocrine organs, and also central nervous system. In 1987, the adipose tissue has been identified as the major site of metabolism of steroid hormones, thereafter, in 1994, it was recognized as an endocrine organ and the leptin being an early secretory products identified. In addition other biologically active substances were being isolated, such as adiponectin, resistin, TNF-a, interleukin-6 and others. The adipokines derived from adipose tissue modulate many metabolic parameters such as control of food intake, energy balance and peripheral insulin sensitivity, for example. Thus, the altered secretion of adipokines by adipose tissue may have metabolic effects may present complex relations with the pathophysiological process of obesity, endothelial dysfunction, inflammation, atherosclerosis and Diabetes mellitus. The understanding of the molecular processes occurring in the adipocytes may provide new tools for the treatment of pathophysiological conditions such as, for example, metabolic syndrome, obesity and diabetes mellitus.

  16. Does bariatric surgery improve adipose tissue function?

    Science.gov (United States)

    Frikke-Schmidt, H.; O’Rourke, R. W.; Lumeng, C. N.; Sandoval, D. A.; Seeley, R. J.

    2017-01-01

    Summary Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. PMID:27272117

  17. Does bariatric surgery improve adipose tissue function?

    Science.gov (United States)

    Frikke-Schmidt, H; O'Rourke, R W; Lumeng, C N; Sandoval, D A; Seeley, R J

    2016-09-01

    Bariatric surgery is currently the most effective treatment for obesity. Not only do these types of surgeries produce significant weight loss but also they improve insulin sensitivity and whole body metabolic function. The aim of this review is to explore how altered physiology of adipose tissue may contribute to the potent metabolic effects of some of these procedures. This includes specific effects on various fat depots, the function of individual adipocytes and the interaction between adipose tissue and other key metabolic tissues. Besides a dramatic loss of fat mass, bariatric surgery shifts the distribution of fat from visceral to the subcutaneous compartment favoring metabolic improvement. The sensitivity towards lipolysis controlled by insulin and catecholamines is improved, adipokine secretion is altered and local adipose inflammation as well as systemic inflammatory markers decreases. Some of these changes have been shown to be weight loss independent, and novel hypothesis for these effects includes include changes in bile acid metabolism, gut microbiota and central regulation of metabolism. In conclusion bariatric surgery is capable of improving aspects of adipose tissue function and do so in some cases in ways that are not entirely explained by the potent effect of surgery. © 2016 World Obesity.

  18. Hounsfield unit dynamics of adipose tissue and non-adipose soft tissue in growing pigs

    DEFF Research Database (Denmark)

    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....

  19. Irbesartan increased PPAR{gamma} activity in vivo in white adipose tissue of atherosclerotic mice and improved adipose tissue dysfunction

    Energy Technology Data Exchange (ETDEWEB)

    Iwai, Masaru; Kanno, Harumi; Senba, Izumi; Nakaoka, Hirotomo; Moritani, Tomozo [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan); Horiuchi, Masatsugu, E-mail: horiuchi@m.ehime-u.ac.jp [Department of Molecular Cardiovascular Biology and Pharmacology, Ehime University Graduate School of Medicine, Shitsukawa, Tohon, Ehime 791-0295 (Japan)

    2011-03-04

    Research highlights: {yields} Atherosclerotic apolipoprotein E-deficient (ApoEKO) mice were treated with irbesartan. {yields} Irbesartan decreased white adipose tissue weight without affecting body weight. {yields} DNA-binding for PPAR{gamma} was increased in white adipose tissue in vivo by irbesartan. {yields} Irbesartan increased adipocyte number in white adipose tissue. {yields} Irbesatan increased the expression of adiponectin and leptin in white adipose tissue. -- Abstract: The effect of the PPAR{gamma} agonistic action of an AT{sub 1} receptor blocker, irbesartan, on adipose tissue dysfunction was explored using atherosclerotic model mice. Adult male apolipoprotein E-deficient (ApoEKO) mice at 9 weeks of age were treated with a high-cholesterol diet (HCD) with or without irbesartan at a dose of 50 mg/kg/day for 4 weeks. The weight of epididymal and retroperitoneal adipose tissue was decreased by irbesartan without changing food intake or body weight. Treatment with irbesartan increased the expression of PPAR{gamma} in white adipose tissue and the DNA-binding activity of PPAR{gamma} in nuclear extract prepared from adipose tissue. The expression of adiponectin, leptin and insulin receptor was also increased by irbesartan. These results suggest that irbesartan induced activation of PPAR{gamma} and improved adipose tissue dysfunction including insulin resistance.

  20. Adipose tissues as endocrine target organs.

    Science.gov (United States)

    Lanthier, Nicolas; Leclercq, Isabelle A

    2014-08-01

    In the context of obesity, white adipocyte hypertrophy and adipose tissue macrophage infiltration result in the production of pro-inflammatory adipocytokines inducing insulin resistance locally but also in distant organs and contributing to low grade inflammatory status associated with the metabolic syndrome. Visceral adipose tissue is believed to play a prominent role. Brown and beige adipose tissues are capable of energy dissipation, but also of cytokine production and their role in dysmetabolic syndrome is emerging. This review focuses on metabolic and inflammatory changes in these adipose depots and contribution to metabolic syndrome. Also we will review surgical and pharmacological procedures to target adiposity as therapeutic interventions to treat obesity-associated disorders.

  1. Improved insulin sensitivity and adipose tissue dysregulation after short-term treatment with pioglitazone in non-diabetic, insulin-resistant subjects.

    Science.gov (United States)

    Hammarstedt, A; Sopasakis, V Rotter; Gogg, S; Jansson, P-A; Smith, U

    2005-01-01

    We examined whether short-term treatment with a thiazolidinedione improves insulin sensitivity in non-obese but insulin-resistant subjects and whether this is associated with an improvement in dysregulated adipose tissue (reduced expression of IRS-1, GLUT4, PPARgamma co-activator 1 and markers of terminal differentiation) that we have previously documented to be associated with insulin resistance. Ten non-diabetic subjects, identified as having low IRS-1 and GLUT-4 protein in adipose cells as markers of insulin resistance, underwent 3 weeks of treatment with pioglitazone. The euglycaemic-hyperinsulinaemic clamp technique was used to measure insulin sensitivity before and after treatment. Serum samples were analysed for glucose, insulin, lipids, total and high-molecular-weight (HMW) adiponectin levels. Biopsies from abdominal subcutaneous adipose tissue were taken, cell size measured, mRNA and protein extracted and quantified using real-time RT-PCR and Western blot. Insulin sensitivity was improved after 3 weeks treatment and circulating total as well as HMW adiponectin increased in all subjects, while no effect was seen on serum lipids. In the adipose cells, gene and protein expression of IRS-1 and PPARgamma co-activator 1 remained unchanged, while adiponectin, adipocyte P 2, uncoupling protein 2, GLUT4 and liver X receptor-alpha increased. Insulin-stimulated tyrosine phosphorylation and p-ser-PKB/Akt increased, while no significant effect of thiazolidinedione treatment was seen on the inflammatory status of the adipose tissue in these non-obese subjects. Short-term treatment with pioglitazone improved insulin sensitivity in the absence of any changes in circulating NEFA or lipid levels. Several markers of adipose cell differentiation, previously shown to be reduced in insulin resistance, were augmented, supporting the concept that insulin resistance in these individuals is associated with impaired terminal differentiation of the adipose cells.

  2. The Adipose Tissue in Farm Animals

    DEFF Research Database (Denmark)

    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...

  3. Regulation of systemic energy homeostasis by serotonin in adipose tissues.

    Science.gov (United States)

    Oh, Chang-Myung; Namkung, Jun; Go, Younghoon; Shong, Ko Eun; Kim, Kyuho; Kim, Hyeongseok; Park, Bo-Yoon; Lee, Ho Won; Jeon, Yong Hyun; Song, Junghan; Shong, Minho; Yadav, Vijay K; Karsenty, Gerard; Kajimura, Shingo; Lee, In-Kyu; Park, Sangkyu; Kim, Hail

    2015-04-13

    Central serotonin (5-HT) is an anorexigenic neurotransmitter in the brain. However, accumulating evidence suggests peripheral 5-HT may affect organismal energy homeostasis. Here we show 5-HT regulates white and brown adipose tissue function. Pharmacological inhibition of 5-HT synthesis leads to inhibition of lipogenesis in epididymal white adipose tissue (WAT), induction of browning in inguinal WAT and activation of adaptive thermogenesis in brown adipose tissue (BAT). Mice with inducible Tph1 KO in adipose tissues exhibit a similar phenotype as mice in which 5-HT synthesis is inhibited pharmacologically, suggesting 5-HT has localized effects on adipose tissues. In addition, Htr3a KO mice exhibit increased energy expenditure and reduced weight gain when fed a high-fat diet. Treatment with an Htr2a antagonist reduces lipid accumulation in 3T3-L1 adipocytes. These data suggest important roles for adipocyte-derived 5-HT in controlling energy homeostasis.

  4. AUTOTRANSPLANTATION OF MESENCHYMAL STEM CELLS FROM ADIPOSE TISSUE – INNOVATIVE PATHOGENETIC METHOD OF TREATMENT OF PATIENTS WITH INCISIONAL HERNIAS (FIRST CASES REPORT

    Directory of Open Access Journals (Sweden)

    V. G. Bogdan

    2012-01-01

    Full Text Available In the article a complex technology of receiving a biological transplant with autologous mesenchymal stem cells from the adipose tissue is presented. Possibility of successful clinical performance of reconstruction of extensive defects of anterior belly wall with the use of a multicomponent biological transplant with autologous mesenchy- mal stem cells from the adipose tissue, differentiated in the fibroblast direction is shown. The use of the proposed method of plasticity promotes the improvement of quality of surgical treatment, expansies the scope of cellular technologies in practical health care, improves the patients quality of life in the postoperative period. 

  5. Renin dynamics in adipose tissue: adipose tissue control of local renin concentrations

    OpenAIRE

    Fowler, Jason D.; Krueth, Stacy B.; Bernlohr, David A.; Katz, Stephen A.

    2009-01-01

    The renin-angiotensin system (RAS) has been implicated in a variety of adipose tissue functions, including tissue growth, differentiation, metabolism, and inflammation. Although expression of all components necessary for a locally derived adipose tissue RAS has been demonstrated within adipose tissue, independence of local adipose RAS component concentrations from corresponding plasma RAS fluctuations has not been addressed. To analyze this, we varied in vivo rat plasma concentrations of two ...

  6. Characterization and comparison of adipose tissue-derived cells from human subcutaneous and omental adipose tissues.

    Science.gov (United States)

    Toyoda, Mito; Matsubara, Yoshinori; Lin, Konghua; Sugimachi, Keizou; Furue, Masutaka

    2009-10-01

    Different fat depots contribute differently to disease and function. These differences may be due to the regional variation in cell types and inherent properties of fat cell progenitors. To address the differences of cell types in the adipose tissue from different depots, the phenotypes of freshly isolated adipose tissue-derived cells (ATDCs) from subcutaneous (SC) and omental (OM) adipose tissues were compared using flow cytometry. Our results showed that CD31(-)CD34(+)CD45(-)CD90(-)CD105(-)CD146(+) population, containing vascular smooth muscle cells and pericytes, was specifically defined in the SC adipose tissue while no such population was observed in OM adipose tissue. On the other hand, CD31(-)CD34(+)CD45(-)CD90(-)CD105(-)CD146(-) population, which is an undefined cell population, were found solely in OM adipose tissue. Overall, the SC adipose tissue contained more ATDCs than OM adipose tissue, while OM adipose tissue contained more blood-derived cells. Regarding to the inherent properties of fat cell progenitors from the two depots, adipose-derived stem cells (ADSCs) from SC had higher capacity to differentiate into both adipogenic and osteogenic lineages than those from OM, regardless of that the proliferation rates of ADSCs from both depots were similar. The higher differentiation capacity of ADSCs from SC adipose tissue suggests that SC tissue is more suitable cell source for regenerative medicine than OM adipose tissue.

  7. Adipose tissue: cell heterogeneity and functional diversity.

    Science.gov (United States)

    Esteve Ràfols, Montserrat

    2014-02-01

    There are two types of adipose tissue in the body whose function appears to be clearly differentiated. White adipose tissue stores energy reserves as fat, whereas the metabolic function of brown adipose tissue is lipid oxidation to produce heat. A good balance between them is important to maintain energy homeostasis. The concept of white adipose tissue has radically changed in the past decades, and is now considered as an endocrine organ that secretes many factors with autocrine, paracrine, and endocrine functions. In addition, we can no longer consider white adipose tissue as a single tissue, because it shows different metabolic profiles in its different locations, with also different implications. Although the characteristic cell of adipose tissue is the adipocyte, this is not the only cell type present in adipose tissue, neither the most abundant. Other cell types in adipose tissue described include stem cells, preadipocytes, macrophages, neutrophils, lymphocytes, and endothelial cells. The balance between these different cell types and their expression profile is closely related to maintenance of energy homeostasis. Increases in adipocyte size, number and type of lymphocytes, and infiltrated macrophages are closely related to the metabolic syndrome diseases. The study of regulation of proliferation and differentiation of preadipocytes and stem cells, and understanding of the interrelationship between the different cell types will provide new targets for action against these diseases. Copyright © 2012 SEEN. Published by Elsevier Espana. All rights reserved.

  8. Development and differentiation of adipose tissue

    Directory of Open Access Journals (Sweden)

    Ivković-Lazar Tatjana A.

    2003-01-01

    Full Text Available 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 organs. With humans there are white and brown adipose tissues, which is predominant with infants and small children. Histologic characteristics From a histological point of view, it is a special form of reticular connective tissue, which contains adipocytes with netlike structure. Human adipose tissue has four types of adrenergic receptors with different topographic dispositions, which manifest different metabolic activity of adipocytes of particular body organs. Changes in adipose tissue are associated with the process of adipocyte differentiation. Critical moments for this process are last months of pregnancy, the first six months of infancy and then puberty. However, the differentiation process may also begin during maturity. Namely, as size of adipocytes can increase to a certain limit, this process can be activated after reaching a 'critical' adipocyte volume. The differentiation process is affected by a number of hormones (insulin, glucagon, corticosteroids, somatotropin (STH, thyroid gland hormones, prolactin, testosterone, but also by some other substances (fatty acids, prostaglandins, liposoluble vitamins, butyrate, aspirin, indomethacin, metylxanthine, etc..

  9. Mitochondria and endocrine function of adipose tissue.

    Science.gov (United States)

    Medina-Gómez, Gema

    2012-12-01

    Excess of adipose tissue is accompanied by an increase in the risk of developing insulin resistance, type 2 diabetes (T2D) and other complications. Nevertheless, total or partial absence of fat or its accumulation in other tissues (lipotoxicity) is also associated to these complications. White adipose tissue (WAT) was traditionally considered a metabolically active storage tissue for lipids while brown adipose tissue (BAT) was considered as a thermogenic adipose tissue with higher oxidative capacity. Nowadays, WAT is also considered an endocrine organ that contributes to energy homeostasis. Experimental evidence tends to link the malfunction of adipose mitochondria with the development of obesity and T2D. This review discusses the importance of mitochondrial function in adipocyte biology and the increased evidences of mitochondria dysfunction in these epidemics. New strategies targeting adipocyte mitochondria from WAT and BAT are also discussed as therapies against obesity and its complications in the near future.

  10. Adipose and mammary epithelial tissue engineering.

    Science.gov (United States)

    Zhu, Wenting; Nelson, Celeste M

    2013-01-01

    Breast reconstruction is a type of surgery for women who have had a mastectomy, and involves using autologous tissue or prosthetic material to construct a natural-looking breast. Adipose tissue is the major contributor to the volume of the breast, whereas epithelial cells comprise the functional unit of the mammary gland. Adipose-derived stem cells (ASCs) can differentiate into both adipocytes and epithelial cells and can be acquired from autologous sources. ASCs are therefore an attractive candidate for clinical applications to repair or regenerate the breast. Here we review the current state of adipose tissue engineering methods, including the biomaterials used for adipose tissue engineering and the application of these techniques for mammary epithelial tissue engineering. Adipose tissue engineering combined with microfabrication approaches to engineer the epithelium represents a promising avenue to replicate the native structure of the breast.

  11. Prolonged niacin treatment leads to increased adipose tissue PUFA synthesis and anti-inflammatory lipid and oxylipin plasma profile.

    Science.gov (United States)

    Heemskerk, Mattijs M; Dharuri, Harish K; van den Berg, Sjoerd A A; Jónasdóttir, Hulda S; Kloos, Dick-Paul; Giera, Martin; van Dijk, Ko Willems; van Harmelen, Vanessa

    2014-12-01

    Prolonged niacin treatment elicits beneficial effects on the plasma lipid and lipoprotein profile that is associated with a protective CVD risk profile. Acute niacin treatment inhibits nonesterified fatty acid release from adipocytes and stimulates prostaglandin release from skin Langerhans cells, but the acute effects diminish upon prolonged treatment, while the beneficial effects remain. To gain insight in the prolonged effects of niacin on lipid metabolism in adipocytes, we used a mouse model with a human-like lipoprotein metabolism and drug response [female APOE*3-Leiden.CETP (apoE3 Leiden cholesteryl ester transfer protein) mice] treated with and without niacin for 15 weeks. The gene expression profile of gonadal white adipose tissue (gWAT) from niacin-treated mice showed an upregulation of the "biosynthesis of unsaturated fatty acids" pathway, which was corroborated by quantitative PCR and analysis of the FA ratios in gWAT. Also, adipocytes from niacin-treated mice secreted more of the PUFA DHA ex vivo. This resulted in an increased DHA/arachidonic acid (AA) ratio in the adipocyte FA secretion profile and in plasma of niacin-treated mice. Interestingly, the DHA metabolite 19,20-dihydroxy docosapentaenoic acid (19,20-diHDPA) was increased in plasma of niacin-treated mice. Both an increased DHA/AA ratio and increased 19,20-diHDPA are indicative for an anti-inflammatory profile and may indirectly contribute to the atheroprotective lipid and lipoprotein profile associated with prolonged niacin treatment.

  12. Troglitazone treatment increases bone marrow adipose tissue volume but does not affect trabecular bone volume in mice

    DEFF Research Database (Denmark)

    Erikstrup, Lise Tornvig; Mosekilde, Leif; Justesen, J;

    2001-01-01

    proliferator activated receptor-gamma (PPARgamma). Histomorphometric analysis of proximal tibia was performed in order to quantitate the amount of trabecular bone volume per total volume (BV/TV %), adipose tissue volume per total volume (AV/TV %), and hematopoietic marrow volume per total volume (HV...

  13. Adipose Tissue Biology: An Update Review

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2009-12-01

    Full Text Available BACKGROUND: Obesity is a major health problem in most countries in the world today. It increases the risk of diabetes, heart disease, fatty liver and some form of cancer. Adipose tissue biology is currently one of the “hot” areas of biomedical science, as fundamental for the development of novel therapeutics for obesity and its related disorders.CONTENT: Adipose tissue consist predominantly of adipocytes, adipose-derived stromal cells (ASCs, vascular endothelial cells, pericytes, fibroblast, macrophages, and extracellular matrix. Adipose tissue metabolism is extremely dynamic, and the supply of and removal of substrates in the blood is acutely regulated according to the nutritional state. Adipose tissue possesses the ability to a very large extent to modulate its own metabolic activities including differentiation of new adipocytes and production of blood vessels as necessary to accommodate increasing fat stores. At the same time, adipocytes signal to other tissue to regulate their energy metabolism in accordance with the body's nutritional state. Ultimately adipocyte fat stores have to match the body's overall surplus or deficit of energy. Obesity causes adipose tissue dysfunction and results in obesity-related disorders. SUMMARY: It is now clear that adipose tissue is a complex and highly active metabolic and endocrine organ. Undestanding the molecular mechanisms underlying obesity and its associated disease cluster is also of great significance as the need for new and more effective therapeutic strategies is more urgent than ever.  KEYWORDS: obesity, adipocyte, adipose, tissue, adipogenesis, angiogenesis, lipid droplet, lipolysis, plasticity, dysfunction.

  14. Effects of T3 treatment on brown adipose tissue and energy expenditure in a patient with craniopharyngioma and hypothalamic obesity.

    Science.gov (United States)

    van Santen, Hanneke M; Schouten-Meeteren, Antoinette Y; Serlie, Mireille; Meijneke, Ruud W H; van Trotsenburg, A S; Verberne, Hein; Holleman, Frits; Fliers, Eric

    2015-01-01

    Patients treated for childhood craniopharyngioma often develop hypothalamic obesity (HO), which has a huge impact on the physical condition and quality of life of these patients. Treatment for HO thus far has been disappointing, and although several different strategies have been attempted, all interventions had only transient effects. Since thyroid hormones increase energy expenditure metabolism (thyroid hormone induced thermogenesis), it was speculated that treatment with tri-iodothyronine (T3) may be beneficial. In 2002, a case report was published on reduction of body weight after T3 treatment for HO. No studies have been reported since. Recent experimental studies in rodents showed that T3 increases brown adipose tissue (BAT) activity via (pre)sympathetic pathways between the hypothalamus and BAT. Our aim was to investigate whether T3 treatment increases BAT activity in a patient with HO resulting from (treatment of) childhood craniopharyngioma. Thyroxine treatment for central hypothyroidism was switched to T3 monotherapy. Serum T3 and free thyroxine (FT4) concentrations were measured twice weekly for 2 months. ¹²³I-MIBG and ¹⁸F-FDG-PET after induction of non-shivering thermogenesis for the assessment of sympathetic and metabolic activity of BAT as well as indirect calorimetry for assessment of resting energy expenditure were performed before and during T3 treatment. No change in sympathetic and metabolic BAT activity, energy expenditure, or BMI was seen during T3 treatment despite the expected changes in thyroid hormone plasma concentrations. We conclude that T3 monotherapy does not seem to be effective in decreasing HO in childhood craniopharyngioma.

  15. Lipolysis in human adipose tissue during exercise

    DEFF Research Database (Denmark)

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

    2002-01-01

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

  16. Imaging white adipose tissue with confocal microscopy.

    Science.gov (United States)

    Martinez-Santibañez, Gabriel; Cho, Kae Won; Lumeng, Carey N

    2014-01-01

    Adipose tissue is composed of a variety of cell types that include mature adipocytes, endothelial cells, fibroblasts, adipocyte progenitors, and a range of inflammatory leukocytes. These cells work in concert to promote nutrient storage in adipose tissue depots and vary widely based on location. In addition, overnutrition and obesity impart significant changes in the architecture of adipose tissue that are strongly associated with metabolic dysfunction. Recent studies have called attention to the importance of adipose tissue microenvironments in regulating adipocyte function and therefore require techniques that preserve cellular interactions and permit detailed analysis of three-dimensional structures in fat. This chapter summarizes our experience with the use of laser scanning confocal microscopy for imaging adipose tissue in rodents.

  17. Is adipose tissue metabolically different at different sites?

    Science.gov (United States)

    Gil, Angel; Olza, Josune; Gil-Campos, Mercedes; Gomez-Llorente, Carolina; Aguilera, Concepción M

    2011-09-01

    This review focuses on metabolic differences of adipose tissue at different sites of the body, with emphasis in pediatrics. Adipose tissue is composed of various cell types, which include adipocytes and other cells of the stromal vascular fraction such as preadipocytes, blood cells, endothelial cells and macrophages. Mammals have two main types of adipose tissue: white adipose tissue (WAT), and brown adipose tissue (BAT), each of which possesses unique cell autonomous properties. WAT and BAT differ at the functional, as well as the morphological and molecular levels. WAT accumulates surplus energy mainly in the form of triacylglycerols and BAT dissipates energy directly as heat. Recently, functional BAT in humans has been located in the neck, supraclavicular, mediastinal and interscapular areas. WAT is distributed throughout the body in the form of two major types: subcutaneous adipose tissue (SWAT) and the intra-abdominal visceral adipose tissue (VWAT). VWAT tissue is associated with insulin resistance, diabetes mellitus, dyslipidaemia, hypertension, atherosclerosis, hepatic steatosis, and overall mortality whereas SWAT and BAT have intrinsic beneficial metabolic properties. Subcutaneous and visceral adipocytes derive from different progenitor cells that exhibit a different gene expression pattern. SWAT responds better to the antilipolytic effects of insulin and other hormones, secrets more adiponectin and less inflammatory cytokines, and is differentially affected by molecules involved in signal transduction as well as drugs compared with VWAT. Current research is investigating various approaches of BAT and SWAT transplantation, including new sources of adipocyte progenitors. This may be important for the potential treatment of childhood obesity.

  18. USE OF AUTOLOGOUS ADIPOSE TISSUE DERIVED STROMAL VASCULAR FRACTION IN TREATMENT OF KNEE OSTEOARTHRITIS AND CHONDRAL LESIONS

    Directory of Open Access Journals (Sweden)

    Vinay

    2015-10-01

    Full Text Available Osteoarthritis is a joint inflammation that results from cartilage degeneration. It can be caused by aging, heredity and injury from trauma or disease. Stromal vascular fraction (SVF, containing large amount of stem cells and other regenerative cells, can be easily obtained from loose connective tissue that is associated with adipose tissue. Here we evaluated safety and clinical efficacy of freshly isolated autologous SVF cells in patients with grade 2 - 4 degenerative osteoarthritis (OA. A total of 31 patients underwent standard liposuction under local anesthesia and SVF cells were isolated and prepared for application into joints. A total of 61 joints, mainly knee and hip joints, were treated with a single dose of SVF cells. 19 patients were fol lowed for minimum 6 weeks for safety and efficacy. Modified KOOS Clinical Score was used to evaluate clinical effect and was based on pain, non - steroid analgesic usage, limping, extent of joint movement, and stiffness evaluation before and at pre - operative , 1 week post - op, 1 month and 6 weeks after the treatment. No serious side effects, systemic infection or cancer was associated with SVF cell therapy. All patients improved after the treatment. Average KOOS score improved from pre - operative 37.5 to post - op erative 6 week average 66.6. All sub scale parameter for pain, symptoms, activity of living & quality of life are also improved. Higher grade of OA were associated with slower healing. In conclusion, here we report a novel and promising treatment approach for patients with degenerative OA that is safe, cost - effective, and relying only on autologous cells, and can be used as one of the minimal invasive treatment modality for osteoarthritis

  19. Thyroid hormone status defines brown adipose tissue activity and browning of white adipose tissues in mice.

    Science.gov (United States)

    Weiner, Juliane; Kranz, Mathias; Klöting, Nora; Kunath, Anne; Steinhoff, Karen; Rijntjes, Eddy; Köhrle, Josef; Zeisig, Vilia; Hankir, Mohammed; Gebhardt, Claudia; Deuther-Conrad, Winnie; Heiker, John T; Kralisch, Susan; Stumvoll, Michael; Blüher, Matthias; Sabri, Osama; Hesse, Swen; Brust, Peter; Tönjes, Anke; Krause, Kerstin

    2016-12-12

    The present study aimed to determine the effect of thyroid hormone dysfunction on brown adipose tissue activity and white adipose tissue browning in mice. Twenty randomized female C57BL/6NTac mice per treatment group housed at room temperature were rendered hypothyroid or hyperthyroid. In-vivo small animal (18)F-FDG PET/MRI was performed to determine the effects of hypo- and hyperthyroidism on BAT mass and BAT activity. Ex-vivo(14)C-acetate loading assay and assessment of thermogenic gene and protein expression permitted analysis of oxidative and thermogenic capacities of WAT and BAT of eu-, hyper and hypothyroid mice. (18)F-FDG PET/MRI revealed a lack of brown adipose tissue activity in hypothyroid mice, whereas hyperthyroid mice displayed increased BAT mass alongside enhanced (18)F-FDG uptake. In white adipose tissue of both, hyper- and hypothyroid mice, we found a significant induction of thermogenic genes together with multilocular adipocytes expressing UCP1. Taken together, these results suggest that both the hyperthyroid and hypothyroid state stimulate WAT thermogenesis most likely as a consequence of enhanced adrenergic signaling or compensation for impaired BAT function, respectively.

  20. Hypertrophic Obesity and Subcutaneous Adipose Tissue Dysfunction

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2014-08-01

    Full Text Available BACKGROUND: Over the past 50 years, scientists have recognized that not all adipose tissue is alike, and that health risk is associated with the location as well as the amount of body fat. Different depots are sufficiently distinct with respect to fatty-acid storage and release as to probably play unique roles in human physiology. Whether fat redistribution causes metabolic disease or whether it is a marker of underlying processes that are primarily responsible is an open question. CONTENT: The limited expandability of the subcutaneous adipose tissue leads to inappropriate adipose cell expansion (hypertrophic obesity with local inflammation and a dysregulated and insulin-resistant adipose tissue. The inability to store excess fat in the subcutaneous adipose tissue is a likely key mechanism for promoting ectopic fat accumulation in tissues and areas where fat can be stored, including the intra-abdominal and visceral areas, in the liver, epi/pericardial area, around vessels, in the myocardium, and in the skeletal muscles. Many studies have implicated ectopic fat accumulation and the associated lipotoxicity as the major determinant of the metabolic complications of obesity driving systemic insulin resistance, inflammation, hepatic glucose production, and dyslipidemia. SUMMARY: In summary, hypertrophic obesity is due to an impaired ability to recruit and differentiate available adipose precursor cells in the subcutaneous adipose tissue. Thus, the subcutaneous adipose tissue may be particular in its limited ability in certain individuals to undergo adipogenesis during weight increase. Inability to promote subcutaneous adipogenesis under periods of affluence would favor lipid overlow and ectopic fat accumulation with negative metabolic consequences. KEYWORDS: obesity, adipogenesis, subcutaneous adipose tissue, visceral adipose tissue, adipocyte dysfunction.

  1. Arthroscopic treatment of chondral defects in the hip: AMIC, MACI, microfragmented adipose tissue transplantation (MATT and other options

    Directory of Open Access Journals (Sweden)

    Jannelli Eugenio

    2017-01-01

    Full Text Available Chondral lesions are currently considered in the hip as a consequence of trauma, osteonecrosis, dysplasia, labral tears, loose bodies, dislocation, previous slipped capital femoral epiphysis and Femoro-Acetabular-Impingement (FAI. The management of chondral lesions is debated and several techniques are described. The physical examination must be carefully performed, followed by radiographs and magnetic resonance imaging (MRI. Differential diagnosis with other pathologies must be considered. Debridement is indicated in patients younger than 50 years with a chondropathy of 1st or 2nd degree. Microfractures are indicated in patients younger than 50 years with a chondropathy of 3rd or 4th degree less than 2 cm2. Matrix-Induced Autologous Chondrocyte Implantation (MACI and Autologous Matrix-Induced Chondrogenesis (AMIC procedures are indicated in patients with full-thickness symptomatic 3rd–4th degree chondral defects, extended 2 cm2 or more. The AMIC procedure has the advantage of a one-step procedure and much less expense. Microfragmented adipose tissue transplantation (MATT is indicated for the treatment of delamination and 1st and 2nd degree chondral lesions, regardless of the age of the patient. Chondral defects are effective when the joint space is not compromised. When the Tonnis classification is two or greater, treatment of chondral lesions should be considered ineffective.

  2. Cardiac adipose tissue and atrial fibrillation: the perils of adiposity.

    Science.gov (United States)

    Hatem, Stéphane N; Redheuil, Alban; Gandjbakhch, Estelle

    2016-04-01

    The amount of adipose tissue that accumulates around the atria is associated with the risk, persistence, and severity of atrial fibrillation (AF). A strong body of clinical and experimental evidence indicates that this relationship is not an epiphenomenon but is the result of complex crosstalk between the adipose tissue and the neighbouring atrial myocardium. For instance, epicardial adipose tissue is a major source of adipokines, inflammatory cytokines, or reactive oxidative species, which can contribute to the fibrotic remodelling of the atrial myocardium. Fibro-fatty infiltrations of the subepicardium could also contribute to the functional disorganization of the atrial myocardium. The observation that obesity is associated with distinct structural and functional remodelling of the atria has opened new perspectives of treating AF substrate with aggressive risk factor management. Advances in cardiac imaging should lead to an improved ability to visualize myocardial fat depositions and to localize AF substrates.

  3. Brown adipose tissue, thermogenesis, angiogenesis: pathophysiological aspects.

    Science.gov (United States)

    Honek, Jennifer; Lim, Sharon; Fischer, Carina; Iwamoto, Hideki; Seki, Takahiro; Cao, Yihai

    2014-07-01

    The number of obese and overweight individuals is globally rising, and obesity-associated disorders such as type 2 diabetes, cardiovascular disease and certain types of cancer are among the most common causes of death. While white adipose tissue is the key player in the storage of energy, active brown adipose tissue expends energy due to its thermogenic capacity. Expanding and activating brown adipose tissue using pharmacological approaches therefore might offer an attractive possibility for therapeutic intervention to counteract obesity and its consequences for metabolic health.

  4. Adipose tissue as an endocrine organ.

    Science.gov (United States)

    McGown, Christine; Birerdinc, Aybike; Younossi, Zobair M

    2014-02-01

    Obesity is one of the most important health challenges faced by developed countries and is increasingly affecting adolescents and children. Obesity is also a considerable risk factor for the development of numerous other chronic diseases, such as insulin resistance, type 2 diabetes, heart disease and nonalcoholic fatty liver disease. The epidemic proportions of obesity and its numerous comorbidities are bringing into focus the highly complex and metabolically active adipose tissue. Adipose tissue is increasingly being considered as a functional endocrine organ. This article discusses the endocrine effects of adipose tissue during obesity and the systemic impact of this signaling.

  5. Transplantation of neural progenitor cells differentiated from adipose tissue-derived stem cells for treatment of sciatic nerve injury

    Institute of Scientific and Technical Information of China (English)

    Shasha Dong§; Na Liu§; Yang Hu ; Ping Zhang; Chao Pan; Youping Zhang; Yingxin Tang; Zhouping Tang 

    2016-01-01

    Objectives: Currently, the clinical repair of sciatic nerve injury remains difficult. Previous studies have confirmed that transplantation of adipose tissue-derived stem cells promotes nerve regeneration and restoration at peripheral nerve injury sites. Methods:In this study, adipose tissue-derived stem cells were induced to differentiate into neural progenitor cells, transfected with a green fluorescent protein-containing lentivirus, and then transplanted into the lesions of rats with sciatic nerve compression injury. Results: Fluorescence microscopy revealed that the transplanted cells survived, migrated, and differentiated in rats. At two weeks post-operation, a large number of transplanted cells had migrated to the injured lesions; at six weeks post-operation, transplanted cells were visible around the injured nerve and several cells were observed to express a Schwann cell marker. Sciatic function index and electrophysiological outcomes of the transplantation group were better than those of the control group. Cell transplantation promoted the recovery of motor nerve conduction velocity and com-pound muscle action potential amplitude, and reduced gastrocnemius muscle atrophy. Conclusions: Our experimental findings indicate that neural progenitor cells, differentiated from adipose tissue-derived stem cells, are potential seed stem cells that can be transplanted into lesions to treat sciatic nerve injury. This provides a theoretical basis for their use in clinical applications.

  6. Molecular pathways regulating the formation of brown-like adipocytes in white adipose tissue.

    Science.gov (United States)

    Fu, Jianfei; Li, Zhen; Zhang, Huiqin; Mao, Yushan; Wang, Anshi; Wang, Xin; Zou, Zuquan; Zhang, Xiaohong

    2015-07-01

    Adipose tissue is functionally composed of brown adipose tissue and white adipose tissue. The unique thermogenic capacity of brown adipose tissue results from expression of uncoupling protein 1 in the mitochondrial inner membrane. On the basis of recent findings that adult humans have functionally active brown adipose tissue, it is now recognized as playing a much more important role in human metabolism than was previously thought. More importantly, brown-like adipocytes can be recruited in white adipose tissue upon environmental stimulation and pharmacologic treatment, and this change is associated with increased energy expenditure, contributing to a lean and healthy phenotype. Thus, the promotion of brown-like adipocyte development in white adipose tissue offers novel possibilities for the development of therapeutic strategies to combat obesity and related metabolic diseases. In this review, we summarize recent advances in understanding the molecular mechanisms involved in the recruitment of brown-like adipocyte in white adipose tissue.

  7. White adipose tissue: getting nervous.

    Science.gov (United States)

    Fliers, E; Kreier, F; Voshol, P J; Havekes, L M; Sauerwein, H P; Kalsbeek, A; Buijs, R M; Romijn, J A

    2003-11-01

    Neuroendocrine research has altered the traditional perspective of white adipose tissue (WAT) as a passive store of triglycerides. In addition to fatty acids, WAT produces many hormones and can therefore be designated as a traditional endocrine gland actively participating in the integrative physiology of fuel and energy metabolism, eating behaviour and the regulation of hormone secretion and sensitivity. WAT is controlled by humoral factors, para- and intracrine factors and by neural regulation. Sympathetic nerve fibres innervate WAT and stimulate lipolysis, leading to the release of glycerol and free fatty acids. In addition, recent research in rats has clearly shown a functional parasympathetic innervation of WAT. There appears to be a distinct somatotopy within the parasympathetic nuclei: separate sets of autonomic neurones in the brain stem innervate either the visceral or the subcutaneous fat compartment. We therefore propose that the central nervous system (CNS) plays a major role in the hitherto unexplained regulation of body fat distribution. Parasympathectomy induces insulin resistance with respect to glucose and fatty acid uptake in the innervated fat depot and has selective effects on local hormone synthesis. Thus, the CNS is involved not only in the regulation of hormone production by WAT, but also in its hormone sensitivity. The developments in this research area are likely to increase our insights in the pathogenesis of metabolic disorders such as hypertriglyceridemia, diabetes mellitus type 2 and lipodystrophy syndromes.

  8. Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues.

    Science.gov (United States)

    Hausman, Gary J; Basu, Urmila; Du, Min; Fernyhough-Culver, Melinda; Dodson, Michael V

    2014-01-01

    Human studies of the influence of aging and other factors on intermuscular fat (INTMF) were reviewed. Intermuscular fat increased with weight loss, weight gain, or with no weight change with age in humans. An increase in INTMF represents a similar threat to type 2 diabetes and insulin resistance as does visceral adipose tissue (VAT). Studies of INTMF in animals covered topics such as quantitative deposition and genetic relationships with other fat depots. The relationship between leanness and higher proportions of INTMF fat in pigs was not observed in human studies and was not corroborated by other pig studies. In humans, changes in muscle mass, strength and quality are associated with INTMF accretion with aging. Gene expression profiling and intrinsic methylation differences in pigs demonstrated that INTMF and VAT are primarily associated with inflammatory and immune processes. It seems that in the pig and humans, INTMF and VAT share a similar pattern of distribution and a similar association of components dictating insulin sensitivity. Studies on intramuscular (IM) adipocyte development in meat animals were reviewed. Gene expression analysis and genetic analysis have identified candidate genes involved in IM adipocyte development. Intramuscular (IM) adipocyte development in human muscle is only seen during aging and some pathological circumstance. Several genetic links between human and meat animal adipogenesis have been identified. In pigs, the Lipin1 and Lipin 2 gene have strong genetic effects on IM accumulation. Lipin1 deficiency results in immature adipocyte development in human lipodystrophy. In humans, overexpression of Perilipin 2 (PLIN2) facilitates intramyocellular lipid accretion whereas in pigs PLIN2 gene expression is associated with IM deposition. Lipins and perilipins may influence intramuscular lipid regardless of species.

  9. Adipose Tissue Remodeling as Homeostatic Inflammation

    Directory of Open Access Journals (Sweden)

    Michiko Itoh

    2011-01-01

    Full Text Available Evidence has accumulated indicating that obesity is associated with a state of chronic, low-grade inflammation. Obese adipose tissue is characterized by dynamic changes in cellular composition and function, which may be referred to as “adipose tissue remodeling”. Among stromal cells in the adipose tissue, infiltrated macrophages play an important role in adipose tissue inflammation and systemic insulin resistance. We have demonstrated that a paracrine loop involving saturated fatty acids and tumor necrosis factor-α derived from adipocytes and macrophages, respectively, aggravates obesity-induced adipose tissue inflammation. Notably, saturated fatty acids, which are released from hypertrophied adipocytes via the macrophage-induced lipolysis, serve as a naturally occurring ligand for Toll-like receptor 4 complex, thereby activating macrophages. Such a sustained interaction between endogenous ligands derived from parenchymal cells and pathogen sensors expressed in stromal immune cells should lead to chronic inflammatory responses ranging from the basal homeostatic state to diseased tissue remodeling, which may be referred to as “homeostatic inflammation”. We, therefore, postulate that adipose tissue remodeling may represent a prototypic example of homeostatic inflammation. Understanding the molecular mechanism underlying homeostatic inflammation may lead to the identification of novel therapeutic strategies to prevent or treat obesity-related complications.

  10. Immunological contributions to adipose tissue homeostasis.

    Science.gov (United States)

    DiSpirito, Joanna R; Mathis, Diane

    2015-09-01

    Adipose tissue is composed of many functionally and developmentally distinct cell types, the metabolic core of which is the adipocyte. The classification of "adipocyte" encompasses three primary types - white, brown, and beige - with distinct origins, anatomic distributions, and homeostatic functions. The ability of adipocytes to store and release lipids, respond to insulin, and perform their endocrine functions (via secretion of adipokines) is heavily influenced by the immune system. Various cell populations of the innate and adaptive arms of the immune system can resist or exacerbate the development of the chronic, low-grade inflammation associated with obesity and metabolic dysfunction. Here, we discuss these interactions, with a focus on their consequences for adipocyte and adipose tissue function in the setting of chronic overnutrition. In addition, we will review the effects of diet composition on adipose tissue inflammation and recent evidence suggesting that diet-driven disruption of the gut microbiota can trigger pathologic inflammation of adipose tissue.

  11. Aetiological factors behind adipose tissue inflammation

    DEFF Research Database (Denmark)

    von Scholten, Bernt J; Andresen, Erik N; Sørensen, Thorkild I A

    2013-01-01

    Despite extensive research into the biological mechanisms behind obesity-related inflammation, knowledge of environmental and genetic factors triggering such mechanisms is limited. In the present narrative review we present potential determinants of adipose tissue inflammation and suggest ways...

  12. How to Measure Adipose Tissue Insulin Sensitivity?

    DEFF Research Database (Denmark)

    Søndergaard, Esben; Espinosa De Ycaza, Ana Elena; Morgan-Bathke, Maria

    2017-01-01

    Background: Adipose tissue insulin resistance may be a proximate cause of hepatic and skeletal muscle insulin resistance by releasing excess FFA. However, no consensus exists on how to quantify adipose tissue insulin sensitivity. We compared three methods for measuring adipose tissue insulin...... sensitivity ranging from the complex multistep pancreatic clamp technique to the simple adipose tissue insulin resistance index (Adipo-IR). Methods: We completed studies of 25 adults with a wide range of insulin sensitivity. The insulin dose resulting in a 50% suppression of palmitate flux (IC50) was measured...... using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. Results: Adipo-IR was reproducible [sample CV=10...

  13. Autologous adipose tissue-derived stem cells treatment demonstrated favorable and sustainable therapeutic effect for Crohn's fistula.

    Science.gov (United States)

    Lee, Woo Yong; Park, Kyu Joo; Cho, Yong Beom; Yoon, Sang Nam; Song, Kee Ho; Kim, Do Sun; Jung, Sang Hun; Kim, Mihyung; Yoo, Hee-Won; Kim, Inok; Ha, Hunjoo; Yu, Chang Sik

    2013-11-01

    Fistula is a representative devastating complication in Crohn's patients due to refractory to conventional therapy and high recurrence. In our phase I clinical trial, adipose tissue-derived stem cells (ASCs) demonstrated their safety and therapeutic potential for healing fistulae associated with Crohn's disease. This study was carried out to evaluate the efficacy and safety of ASCs in patients with Crohn's fistulae. In this phase II study, forty-three patients were treated with ASCs. The amount of ASCs was proportioned to fistula size and fistula tract was filled with ASCs in combination with fibrin glue after intralesional injection of ASCs. Patients without complete closure of fistula at 8 weeks received a second injection of ASCs containing 1.5 times more cells than the first injection. Fistula healing at week 8 after final dose injection and its sustainability for 1-year were evaluated. Healing was defined as a complete closure of external opening without any sign of drainage and inflammation. A modified per-protocol analysis showed that complete fistula healing was observed in 27/33 patients (82%) by 8 weeks after ASC injection. Of 27 patients with fistula healing, 26 patients completed additional observation study for 1-year and 23 patients (88%) sustained complete closure. There were no adverse events related to ASC administration. ASC treatment for patients with Crohn's fistulae was well tolerated, with a favorable therapeutic outcome. Furthermore, complete closure was well sustained. These results strongly suggest that autologous ASC could be a novel treatment option for the Crohn's fistula with high-risk of recurrence. Copyright © 2013 AlphaMed Press.

  14. [Kidney, adipose tissue, adipocytes--what's new?].

    Science.gov (United States)

    Lafontan, Max

    2011-04-01

    Increased evidence suggests that obesity-related glomerulopathy and chronic kidney diseases should be identified as isolated complications of obesity. It is questioned if the numerous adipose tissue productions could play a role in the initiation/maintenance of such kidney diseases. This review will provide a sum-up of recent advances on fat cell metabolism and adipose tissue physiology. The adipose tissue behaves as an endocrine organ with multiple activities. It is secreting hormones (leptin, adiponectin, apelin) and numerous factors with autocrine, paracrine and systemic effects. These secretions are coming from adipocytes themselves or from cells present in the stroma-vascular fraction of the adipose tissue. When expanding, the adipose tissue of the obese is infiltrated by immune cells such as macrophages and lymphocytes; the role of which is not fully clarified. An attempt will be done to delineate if alterations of lipid storage/fatty acid release or of the secretion potencies of adipose tissue could contribute to kidney lipotoxicity and other chronic kidney diseases described in the obese. Copyright © 2010 Association Société de néphrologie. Published by Elsevier SAS. All rights reserved.

  15. How to Measure Adipose Tissue Insulin Sensitivity.

    Science.gov (United States)

    Søndergaard, Esben; Espinosa De Ycaza, Ana Elena; Morgan-Bathke, Maria; Jensen, Michael D

    2017-04-01

    Adipose tissue insulin resistance may cause hepatic and skeletal muscle insulin resistance by releasing excess free fatty acids (FFAs). Because no consensus exists on how to quantify adipose tissue insulin sensitivity we compared three methods for measuring adipose tissue insulin sensitivity: the single step insulin clamp, the multistep pancreatic clamp, and the adipose tissue insulin resistance index (Adipo-IR). We studied insulin sensitivity in 25 adults by measuring the insulin concentration resulting in 50% suppression of palmitate flux (IC50) using both a multistep pancreatic clamp and a one-step hyperinsulinemic-euglycemic clamp. Palmitate kinetics were measured using a continuous infusion of [U-13C]palmitate. Adipo-IR was calculated from fasting insulin and fasting FFA concentrations. Adipo-IR was reproducible (sample coefficient of variability, 10.0%) and correlated with the IC50 measured by the multistep pancreatic clamp technique (r, 0.86; P adipose tissue insulin sensitivity. However, age and physical fitness systematically affect the predictive values. Although Adipo-IR is suitable for larger population studies, the multistep pancreatic clamp technique is probably needed for mechanistic studies of adipose tissue insulin action.

  16. Vitamin D signalling in adipose tissue.

    Science.gov (United States)

    Ding, Cherlyn; Gao, Dan; Wilding, John; Trayhurn, Paul; Bing, Chen

    2012-12-14

    Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function.

  17. Brown Adipose Tissue Growth and Development

    Directory of Open Access Journals (Sweden)

    Michael E. Symonds

    2013-01-01

    Full Text Available Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

  18. Brown adipose tissue growth and development.

    Science.gov (United States)

    Symonds, Michael E

    2013-01-01

    Brown adipose tissue is uniquely able to rapidly produce large amounts of heat through activation of uncoupling protein (UCP) 1. Maximally stimulated brown fat can produce 300 watts/kg of heat compared to 1 watt/kg in all other tissues. UCP1 is only present in small amounts in the fetus and in precocious mammals, such as sheep and humans; it is rapidly activated around the time of birth following the substantial rise in endocrine stimulatory factors. Brown adipose tissue is then lost and/or replaced with white adipose tissue with age but may still contain small depots of beige adipocytes that have the potential to be reactivated. In humans brown adipose tissue is retained into adulthood, retains the capacity to have a significant role in energy balance, and is currently a primary target organ in obesity prevention strategies. Thermogenesis in brown fat humans is environmentally regulated and can be stimulated by cold exposure and diet, responses that may be further modulated by photoperiod. Increased understanding of the primary factors that regulate both the appearance and the disappearance of UCP1 in early life may therefore enable sustainable strategies in order to prevent excess white adipose tissue deposition through the life cycle.

  19. Tissue engineering chamber promotes adipose tissue regeneration in adipose tissue engineering models through induced aseptic inflammation.

    Science.gov (United States)

    Peng, Zhangsong; Dong, Ziqing; Chang, Qiang; Zhan, Weiqing; Zeng, Zhaowei; Zhang, Shengchang; Lu, Feng

    2014-11-01

    Tissue engineering chamber (TEC) makes it possible to generate significant amounts of mature, vascularized, stable, and transferable adipose tissue. However, little is known about the role of the chamber in tissue engineering. Therefore, to investigate the role of inflammatory response and the change in mechanotransduction started by TEC after implantation, we placed a unique TEC model on the surface of the groin fat pads in rats to study the expression of cytokines and tissue development in the TEC. The number of infiltrating cells was counted, and vascular endothelial growth factor (VEGF) and monocyte chemotactic protein-1 (MCP-1) expression levels in the chamber at multiple time points postimplantation were analyzed by enzyme-linked immunosorbent assay. Tissue samples were collected at various time points and labeled for specific cell populations. The result showed that new adipose tissue formed in the chamber at day 60. Also, the expression of MCP-1 and VEGF in the chamber decreased slightly from an early stage as well as the number of the infiltrating cells. A large number of CD34+/perilipin- perivascular cells could be detected at day 30. Also, the CD34+/perilipin+ adipose precursor cell numbers increased sharply by day 45 and then decreased by day 60. CD34-/perilipin+ mature adipocytes were hard to detect in the chamber content at day 30, but their number increased and then peaked at day 60. Ki67-positive cells could be found near blood vessels and their number decreased sharply over time. Masson's trichrome showed that collagen was the dominant component of the chamber content at early stage and was replaced by newly formed small adipocytes over time. Our findings suggested that the TEC implantation could promote the proliferation of adipose precursor cells derived from local adipose tissue, increase angiogenesis, and finally lead to spontaneous adipogenesis by inducing aseptic inflammation and changing local mechanotransduction.

  20. Insulin effects in muscle and adipose tissue.

    Science.gov (United States)

    Dimitriadis, George; Mitrou, Panayota; Lambadiari, Vaia; Maratou, Eirini; Raptis, Sotirios A

    2011-08-01

    The major effects of insulin on muscle and adipose tissue are: (1) Carbohydrate metabolism: (a) it increases the rate of glucose transport across the cell membrane, (b) it increases the rate of glycolysis by increasing hexokinase and 6-phosphofructokinase activity, (c) it stimulates the rate of glycogen synthesis and decreases the rate of glycogen breakdown. (2) Lipid metabolism: (a) it decreases the rate of lipolysis in adipose tissue and hence lowers the plasma fatty acid level, (b) it stimulates fatty acid and triacylglycerol synthesis in tissues, (c) it increases the uptake of triglycerides from the blood into adipose tissue and muscle, (d) it decreases the rate of fatty acid oxidation in muscle and liver. (3) Protein metabolism: (a) it increases the rate of transport of some amino acids into tissues, (b) it increases the rate of protein synthesis in muscle, adipose tissue, liver, and other tissues, (c) it decreases the rate of protein degradation in muscle (and perhaps other tissues). These insulin effects serve to encourage the synthesis of carbohydrate, fat and protein, therefore, insulin can be considered to be an anabolic hormone. Copyright © 2011 Elsevier Ireland Ltd. All rights reserved.

  1. White adipose tissue resilience to insulin deprivation and replacement.

    Science.gov (United States)

    Hadji, Lilas; Berger, Emmanuelle; Soula, Hédi; Vidal, Hubert; Géloën, Alain

    2014-01-01

    Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. The initial body weight of the rats was 465±5.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues.

  2. White Adipose Tissue Resilience to Insulin Deprivation and Replacement

    Science.gov (United States)

    Hadji, Lilas; Berger, Emmanuelle; Soula, Hédi; Vidal, Hubert; Géloën, Alain

    2014-01-01

    Introduction Adipocyte size and body fat distribution are strongly linked to the metabolic complications of obesity. The aim of the present study was to test the plasticity of white adipose tissue in response to insulin deprivation and replacement. We have characterized the changes of adipose cell size repartition and gene expressions in type 1 diabetes Sprague-Dawley rats and type 1 diabetic supplemented with insulin. Methods Using streptozotocin (STZ)-induced diabetes, we induced rapid changes in rat adipose tissue weights to study the changes in the distribution of adipose cell sizes in retroperitoneal (rWAT), epididymal (eWAT) and subcutaneous adipose tissues (scWAT). Adipose tissue weights of type 1 diabetic rats were then rapidly restored by insulin supplementation. Cell size distributions were analyzed using multisizer IV (Beckman Coulter). Cell size changes were correlated to transcriptional regulation of genes coding for proteins involved in lipid and glucose metabolisms and adipocytokines. Results The initial body weight of the rats was 465±5.2 g. Insulin privation was stopped when rats lost 100 g which induced reductions in fat mass of 68% for rWAT, 42% for eWAT and 59% for scWAT corresponding to decreased mode cell diameters by 31.1%, 20%, 25.3%, respectively. The most affected size distribution by insulin deprivation was observed in rWAT. The bimodal distribution of adipose cell sizes disappeared in response to insulin deprivation in rWAT and scWAT. The most important observation is that cell size distribution returned close to control values in response to insulin treatment. mRNAs coding for adiponectin, leptin and apelin were more stimulated in scWAT compared to other depots in diabetic plus insulin group. Conclusion Fat depots have specific responses to insulin deprivation and supplementation. The results show that insulin is a major determinant of bimodal cell repartition in adipose tissues. PMID:25170835

  3. Adipose Tissue Dysfunction in Nascent Metabolic Syndrome

    Directory of Open Access Journals (Sweden)

    Andrew A. Bremer

    2013-01-01

    Full Text Available The metabolic syndrome (MetS confers an increased risk for both type 2 diabetes mellitus (T2DM and cardiovascular disease (CVD. Moreover, studies on adipose tissue biology in nascent MetS uncomplicated by T2DM and/or CVD are scanty. Recently, we demonstrated that adipose tissue dysregulation and aberrant adipokine secretion contribute towards the syndrome’s low-grade chronic proinflammatory state and insulin resistance. Specifically, we have made the novel observation that subcutaneous adipose tissue (SAT in subjects with nascent MetS has increased macrophage recruitment with cardinal crown-like structures. We have also shown that subjects with nascent MetS have increased the levels of SAT-secreted adipokines (IL-1, IL-6, IL-8, leptin, RBP-4, CRP, SAA, PAI-1, MCP-1, and chemerin and plasma adipokines (IL-1, IL-6, leptin, RBP-4, CRP, SAA, and chemerin, as well as decreased levels of plasma adiponectin and both plasma and SAT omentin-1. The majority of these abnormalities persisted following correction for increased adiposity. Our data, as well as data from other investigators, thus, highlight the importance of subcutaneous adipose tissue dysfunction in subjects with MetS and its contribution to the proinflammatory state and insulin resistance. This adipokine profile may contribute to increased insulin resistance and low-grade inflammation, promoting the increased risk of T2DM and CVD.

  4. Lipophilic Micronutrients and Adipose Tissue Biology

    Directory of Open Access Journals (Sweden)

    Franck Tourniaire

    2012-11-01

    Full Text Available Lipophilic micronutrients (LM constitute a large family of molecules including several vitamins (A, D, E, K and carotenoids. Their ability to regulate gene expression is becoming increasingly clear and constitutes an important part of nutrigenomics. Interestingly, adipose tissue is not only a main storage site for these molecules within the body, but it is also subjected to the regulatory effects of LM. Indeed, several gene regulations have been described in adipose tissue that could strongly impact its biology with respect to the modulation of adipogenesis, inflammatory status, or energy homeostasis and metabolism, among others. The repercussions in terms of health effects of such regulations in the context of obesity and associated pathologies represent an exciting and emerging field of research. The present review will focus on the regulatory effects of vitamin A, D, E and K as well as carotenoids on adipose tissue biology and physiology, notably in the context of obesity and associated disorders.

  5. Characteristic expression of extracellular matrix in subcutaneous adipose tissue development and adipogenesis; comparison with visceral adipose tissue.

    Science.gov (United States)

    Mori, Shinobu; Kiuchi, Satomi; Ouchi, Atsushi; Hase, Tadashi; Murase, Takatoshi

    2014-01-01

    Adipose tissue is a connective tissue specified for energy metabolism and endocrines, but functional differences between subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) have not been fully elucidated. To reveal the physiological role of SAT, we characterized in vivo tissue development and in vitro adipocyte differentiation. In a DNA microarray analysis of SAT and VAT in Wistar rats, functional annotation clusters of extracellular matrix (ECM)-related genes were found in SAT, and major ECM molecules expressed in adipose tissues were profiled. In a histological analysis and quantitative expression analysis, ECM expression patterns could be classified into two types: (i) a histogenesis-correlated type such as type IV and XV collagen, and laminin subunits, (ii) a high-SAT expression type such as type I, III, and V collagen and minor characteristic collagens. Type (i) was related to basal membrane and up-regulated in differentiated 3T3-L1 cells and in histogenesis at depot-specific timings. In contrast, type (ii) was related to fibrous forming and highly expressed in 3T3-L1 preadipocytes. Exceptionally, fibronectin was abundant in developed adipose tissue, although it was highly expressed in 3T3-L1 preadipocytes. The present study showed that adipose tissues site-specifically regulate molecular type and timing of ECM expression, and suggests that these characteristic ECM molecules provide a critical microenvironment, which may affect bioactivity of adipocyte itself and interacts with other tissues. It must be important to consider the depot-specific property for the treatment of obesity-related disorders, dermal dysfunction and for the tissue regeneration.

  6. A stringent validation of mouse adipose tissue identity markers.

    Science.gov (United States)

    de Jong, Jasper M A; Larsson, Ola; Cannon, Barbara; Nedergaard, Jan

    2015-06-15

    The nature of brown adipose tissue in humans is presently debated: whether it is classical brown or of brite/beige nature. The dissimilar developmental origins and proposed distinct functions of the brown and brite/beige tissues make it essential to ascertain the identity of human depots with the perspective of recruiting and activating them for the treatment of obesity and type 2 diabetes. For identification of the tissues, a number of marker genes have been proposed, but the validity of the markers has not been well documented. We used established brown (interscapular), brite (inguinal), and white (epididymal) mouse adipose tissues and corresponding primary cell cultures as validators and examined the informative value of a series of suggested markers earlier used in the discussion considering the nature of human brown adipose tissue. Most of these markers unexpectedly turned out to be noninformative concerning tissue classification (Car4, Cited1, Ebf3, Eva1, Fbxo31, Fgf21, Lhx8, Hoxc8, and Hoxc9). Only Zic1 (brown), Cd137, Epsti1, Tbx1, Tmem26 (brite), and Tcf21 (white) proved to be informative in these three tissues. However, the expression of the brite markers was not maintained in cell culture. In a more extensive set of adipose depots, these validated markers provide new information about depot identity. Principal component analysis supported our single-gene conclusions. Furthermore, Zic1, Hoxc8, Hoxc9, and Tcf21 displayed anteroposterior expression patterns, indicating a relationship between anatomic localization and adipose tissue identity (and possibly function). Together, the observed expression patterns of these validated marker genes necessitates reconsideration of adipose depot identity in mice and humans.

  7. Hypothalamus-adipose tissue crosstalk: neuropeptide Y and the regulation of energy metabolism.

    Science.gov (United States)

    Zhang, Wei; Cline, Mark A; Gilbert, Elizabeth R

    2014-01-01

    Neuropeptide Y (NPY) is an orexigenic neuropeptide that plays a role in regulating adiposity by promoting energy storage in white adipose tissue and inhibiting brown adipose tissue activation in mammals. This review describes mechanisms underlying NPY's effects on adipose tissue energy metabolism, with an emphasis on cellular proliferation, adipogenesis, lipid deposition, and lipolysis in white adipose tissue, and brown fat activation and thermogenesis. In general, NPY promotes adipocyte differentiation and lipid accumulation, leading to energy storage in adipose tissue, with effects mediated mainly through NPY receptor sub-types 1 and 2. This review highlights hypothalamus-sympathetic nervous system-adipose tissue innervation and adipose tissue-hypothalamus feedback loops as pathways underlying these effects. Potential sources of NPY that mediate adipose effects include the bloodstream, sympathetic nerve terminals that innervate the adipose tissue, as well as adipose tissue-derived cells. Understanding the role of central vs. peripherally-derived NPY in whole-body energy balance could shed light on mechanisms underlying the pathogenesis of obesity. This information may provide some insight into searching for alternative therapeutic strategies for the treatment of obesity and associated diseases.

  8. Browning and thermogenic programing of adipose tissue.

    Science.gov (United States)

    Kiefer, Florian W

    2016-08-01

    The view of adipose tissue as solely a fat storing organ has changed significantly over the past two decades with the discoveries of numerous adipocyte-secreted factors, so called adipokines, and their endocrine functions throughout the body. The newest chapter added to this story is the finding that adipose tissue is also a thermogenic organ contributing to energy expenditure through actions of specialized, heat-producing brown or beige adipocytes. In contrast to bone fide brown adipocytes, beige cells develop within white fat depots in response to various stimuli such as prolonged cold exposure, underscoring the great thermogenic plasticity of adipose tissue. The energy dissipating properties of beige and/or brown adipocytes hold great promise as a novel therapeutic concept against obesity and related complications. Hence, identifying the specific thermogenic adipocyte populations in humans and their pathways of activation are key milestones of current metabolism research. Here we will discuss the recent advances in the understanding of the molecular and physiological mechanisms of adipose tissue browning. Copyright © 2016 Elsevier Ltd. All rights reserved.

  9. [White adipose tissue dysfunction observed in obesity].

    Science.gov (United States)

    Lewandowska, Ewa; Zieliński, Andrzej

    2016-05-01

    Obesity is a disease with continuingly increasing prevalence. It occurs worldwide independently of age group, material status or country of origin. At these times the most common reasons for obesity are bad eating habits and dramatic reduction of physical activity, which cause the energy imbalance of organism. Fundamental alteration observed in obese subjects is white adipose tissue overgrowth, which is linked to increased incidence of obesity-related comorbidities, such as: cardiovascular diseases, type 2 diabetes or digestive tract diseases. What is more, obesity is also a risk factor for some cancers. Special risk for diseases linked to excessive weight is associated with overgrowth of visceral type of adipose tissue. Adipose tissue, which is the main energy storehouse in body and acts also as an endocrine organ, undergoes both the morphological and the functional changes in obesity, having a negative impact on whole body function. In this article we summarize the most important alterations in morphology and function of white adipose tissue, observed in obese subjects.

  10. Determinants of human adipose tissue gene expression

    DEFF Research Database (Denmark)

    Viguerie, Nathalie; Montastier, Emilie; Maoret, Jean-José

    2012-01-01

    Weight control diets favorably affect parameters of the metabolic syndrome and delay the onset of diabetic complications. The adaptations occurring in adipose tissue (AT) are likely to have a profound impact on the whole body response as AT is a key target of dietary intervention. Identification ...

  11. Epicardial adipose tissue in endocrine and metabolic diseases.

    Science.gov (United States)

    Iacobellis, Gianluca

    2014-05-01

    Epicardial adipose tissue has recently emerged as new risk factor and active player in metabolic and cardiovascular diseases. Albeit its physiological and pathological roles are not completely understood, a body of evidence indicates that epicardial adipose tissue is a fat depot with peculiar and unique features. Epicardial fat is able to synthesize, produce, and secrete bioactive molecules which are then transported into the adjacent myocardium through vasocrine and/or paracrine pathways. Based on these evidences, epicardial adipose tissue can be considered an endocrine organ. Epicardial fat is also thought to provide direct heating to the myocardium and protect the heart during unfavorable hemodynamic conditions, such as ischemia or hypoxia. Epicardial fat has been suggested to play an independent role in the development and progression of obesity- and diabetes-related cardiac abnormalities. Clinically, the thickness of epicardial fat can be easily and accurately measured. Epicardial fat thickness can serve as marker of visceral adiposity and visceral fat changes during weight loss interventions and treatments with drugs targeting the fat. The potential of modulating the epicardial fat with targeted pharmacological agents can open new avenues in the pharmacotherapy of endocrine and metabolic diseases. This review article will provide Endocrine's reader with a focus on epicardial adipose tissue in endocrinology. Novel, established, but also speculative findings on epicardial fat will be discussed from the unexplored perspective of both clinical and basic Endocrinologist.

  12. Visceral Adiposity Index: An Indicator of Adipose Tissue Dysfunction

    Directory of Open Access Journals (Sweden)

    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.

  13. Sustainable three-dimensional tissue model of human adipose tissue.

    Science.gov (United States)

    Bellas, Evangelia; Marra, Kacey G; Kaplan, David L

    2013-10-01

    The need for physiologically relevant sustainable human adipose tissue models is crucial for understanding tissue development, disease progression, in vitro drug development and soft tissue regeneration. The coculture of adipocytes differentiated from human adipose-derived stem cells, with endothelial cells, on porous silk protein matrices for at least 6 months is reported, while maintaining adipose-like outcomes. Cultures were assessed for structure and morphology (Oil Red O content and CD31 expression), metabolic functions (leptin, glycerol production, gene expression for GLUT4, and PPARγ) and cell replication (DNA content). The cocultures maintained size and shape over this extended period in static cultures, while increasing in diameter by 12.5% in spinner flask culture. Spinner flask cultures yielded improved adipose tissue outcomes overall, based on structure and function, when compared to the static cultures. This work establishes a tissue model system that can be applied to the development of chronic metabolic dysfunction systems associated with human adipose tissue, such as obesity and diabetes, due to the long term sustainable functions demonstrated here.

  14. Short term 13-cis-retinoic acid treatment at therapeutic doses elevates expression of leptin, GLUT4, PPARgamma and aP2 in rat adipose tissue.

    Science.gov (United States)

    Krskova-Tybitanclova, K; Macejova, D; Brtko, J; Baculikova, M; Krizanova, O; Zorad, S

    2008-12-01

    Temporary defects in the plasma lipid and glucose homeostasis are frequent complication accompanying chronic treatment with 13-cis-retinoic acid (13cRA). White adipose tissue acts as an endocrine organ producing a variety of hormones (adipocytokines) including leptin, adiponectin, tumor-necrosis factor alpha (TNFalpha) and angiotensin II (Ang II), which influence lipid metabolism, systemic insulin sensitivity and inflammation. To study the effect of a short-term 13cRA administration on metabolism of epididymal fat tissue, we treated Wistar rats with five identical therapeutic doses of 13cRA (0.8 mg/kg b.w.) by gavage during a period of 10 days. Expression of adiponectin, leptin, TNFalpha and selected proteins such as adipocyte fatty acid binding protein (aP2), insulin-dependent glucose transporter GLUT4, peroxisome proliferator-activated receptor gamma (PPARgamma) and retinoid X receptors (RXRs) was investigated using RT-PCR. Short-term treatment with therapeutic doses of 13cRA caused significant increase of the aP2, PPARgamma and moderately RXRalpha gene expression. Similarly, the relative amount of mRNA for leptin and GLUT4 was increased, while the TNFa transcript was decreased after treatment with 13cRA. The gene expression and plasma concentration of adiponectin were without any significant changes. Since local adipose renin-angiotensin system (RAS) has been presumed to be involved in the regulation of fat tissue metabolism, we also investigated the gene expression of RAS components in epididymal fat depot. Our data has shown that 13cRA elevated Ang II receptor type 1 (AT(1) receptor)--at both, mRNA and protein level. Thus, our results demonstrate that short-term 13cRA treatment is inducing alterations in fat tissue metabolism in relation to stimulated adipogenesis.

  15. The Facial Adipose Tissue: A Revision.

    Science.gov (United States)

    Kruglikov, Ilja; Trujillo, Oscar; Kristen, Quick; Isac, Kerelos; Zorko, Julia; Fam, Maria; Okonkwo, Kasie; Mian, Asima; Thanh, Hyunh; Koban, Konstantin; Sclafani, Anthony P; Steinke, Hanno; Cotofana, Sebastian

    2016-12-01

    Recent advantages in the anatomical understanding of the face have turned the focus toward the subcutaneous and deep facial fat compartments. During facial aging, these fat-filled compartments undergo substantial changes along with other structures in the face. Soft tissue filler and fat grafting are valid methods to fight the signs of facial aging, but little is known about their precise effect on the facial fat. This narrative review summarizes the current knowledge about the facial fat compartments in terms of anatomical location, histologic appearance, immune-histochemical characteristics, cellular interactions, and therapeutic options. Three different types of facial adipose tissue can be identified, which are located either superficially (dermal white adipose tissue) or deep (subcutaneous white adipose tissue): fibrous (perioral locations), structural (major parts of the midface), and deposit (buccal fat pad and deep temporal fat pad). These various fat types differ in the size of the adipocytes and the collagenous composition of their extracellular matrix and thus in their mechanical properties. Minimal invasive (e.g., soft tissue fillers or fat grafting) and surgical interventions aiming to restore the youthful face have to account for the different fat properties in various facial areas. However, little is known about the macro- and microscopic characteristics of the facial fat tissue in different compartments and future studies are needed to reveal new insights to better understand the process of aging and how to fight its signs best.

  16. Adipose tissue remodeling in pathophysiology of obesity.

    Science.gov (United States)

    Lee, Mi-Jeong; Wu, Yuanyuan; Fried, Susan K

    2010-07-01

    Recent studies demonstrate that adipose tissue undergoes a continuous process of remodeling that is pathologically accelerated in the obese state. Contrary to earlier dogma, adipocytes die and are replaced by newly differentiated ones. This review will summarize recent advances of our knowledge of the mechanisms that regulate adipose tissue remodeling and highlight the influences of obesity, depot, and sex, as well as the relevance of rodent models to humans. A substantial literature now points to the importance of dynamic changes in adipocyte and immune cell turnover, angiogenesis, and extracellular matrix remodeling in regulating the expandability and functional integrity of this tissue. In obesity, the macrophages are recruited, surrounding dead adipocytes and polarized toward an inflammatory phenotype. The number of dead adipocytes is closely associated with the pathophysiological consequences of obesity, including insulin resistance and hepatic steatosis. Further, there are substantial depot, sex and species differences in the extent of remodeling. Adipose tissue undergoes a continuous remodeling process that normally maintains tissue health, but may spin out of control and lead to adipocyte death in association with the recruitment and activation of macrophages, and systemic insulin resistance.

  17. Browning of white adipose tissue: role of hypothalamic signaling.

    Science.gov (United States)

    Bi, Sheng; Li, Lin

    2013-10-01

    Two types of fat, white adipose tissue (WAT) and brown adipose tissue (BAT), exist in mammals including adult humans. While WAT stores excess calories and an excessive accumulation of fat causes obesity, BAT dissipates energy to produce heat through nonshivering thermogenesis for protection against cold environments and provides the potential for the development of novel anti-obesity treatments. The hypothalamus plays a central role in the control of energy balance. Specifically, recent observations indicate the importance of the dorsomedial hypothalamus (DMH) in thermoregulation. We have found that the orexigenic neuropeptide Y (NPY) in the DMH has distinct actions in modulating adiposity and BAT thermogenesis. Knockdown of NPY in the DMH elevates the thermogenic activity of classic BAT and promotes the development of brown adipocytes in WAT, leading to increased thermogenesis. These findings identify a novel potential target for combating obesity.

  18. Physiological and pathological impact of exosomes of adipose tissue.

    Science.gov (United States)

    Zhang, Yan; Yu, Mei; Tian, Weidong

    2016-02-01

    Exosomes are nanovesicles that have emerged as a new intercellular communication system for transporting proteins and RNAs; recent studies have shown that they play a role in many physiological and pathological processes such as immune regulation, cell differentiation, infection and cancer. By transferring proteins, mRNAs and microRNAs, exosomes act as information vehicles that alter the behavior of recipient cells. Compared to direct cell-cell contact or secreted factors, exosomes can affect recipient cells in more efficient ways. In whole adipose tissues, it has been shown that exosomes exist in supernatants of adipocytes and adipose stromal cells (ADSCs). Adipocyte exosomes are linked to lipid metabolism and obesity-related insulin resistance and exosomes secreted by ADSCs are involved in angiogenesis, immunomodulation and tumor development. This review introduces characteristics of exosomes in adipose tissue, summarizes their functions in different physiological and pathological processes and provides the further insight into potential application of exosomes to disease diagnosis and treatment.

  19. Proteomic characterization of adipose tissue constituents, a necessary step for understanding adipose tissue complexity.

    Science.gov (United States)

    Peinado, Juan R; Pardo, María; de la Rosa, Olga; Malagón, Maria M

    2012-02-01

    The original concept of adipose tissue as an inert storage depot for the excess of energy has evolved over the last years and it is now considered as one of the most important organs regulating body homeostasis. This conceptual change has been supported by the demonstration that adipose tissue serves as a major endocrine organ, producing a wide variety of bioactive molecules, collectively termed adipokines, with endocrine, paracrine and autocrine activities. Adipose tissue is indeed a complex organ wherein mature adipocytes coexist with the various cell types comprising the stromal-vascular fraction (SVF), including preadipocytes, adipose-derived stem cells, perivascular cells, and blood cells. It is known that not only mature adipocytes but also the components of SVF produce adipokines. Furthermore, adipokine production, proliferative and metabolic activities and response to regulatory signals (i.e. insulin, catecholamines) differ between the different fat depots, which have been proposed to underlie their distinct association to specific diseases. Herein, we discuss the recent proteomic studies on adipose tissue focused on the analysis of the separate cellular components and their secretory products, with the aim of identifying the basic features and the contribution of each component to different adipose tissue-associated pathologies.

  20. Oestrone sulphate, adipose tissue, and breast cancer.

    Science.gov (United States)

    Hawkins, R A; Thomson, M L; Killen, E

    1985-01-01

    Oestrone sulphate, the oestrogen in highest concentration in the plasma, may play a role in the induction and growth of breast cancers. By enzymolysis and radioimmunoassay, oestrone sulphate concentrations were measured in 3 biological fluids. High concentrations of the conjugate (up to 775 nmol/l) were detected in breast cyst fluids from some premenopausal women, the concentrations in blood plasma (0.91-4.45 nmol/l) being much lower. Concentrations in the plasmas from postmenopausal women with (0.23-4.63 nmol/l) or without (0.18-1.27 nmol/l) breast cancer were still lower. Oestrone sulphate concentration in cow's milk or cream (0.49-0.67 nmol/l) was also low: dietary intake in these fluids is probably of little consequence. The capacity of breast tissues for hydrolysis of oestrone sulphate was examined in two ways: In tissue slices incubated with 85 pM (3H) oestrone sulphate solution at 37 degrees C, cancers (131-412 fmol/g tissue/hr) and adipose tissues (23-132 fmol/g tissue/hr) hydrolysed significantly more sulphate than did benign tissues (1-36 fmol/g tissue/hr). In tissue homogenates incubated with 5-25 microM [3H] oestrone sulphate at 37 degrees much higher capacities for hydrolysis (nmol/g tissue/hr) were demonstrated with a Km of 2-16.5 microM: cancers (34-394) and benign tissues (9-485) had significantly higher sulphatase activities than adipose tissues (9-39). On a protein basis, however, the sulphatase activities in the 3 tissues were comparable. It is concluded that oestrone sulphate is present in breast cysts and blood plasma and that in vitro, the conjugated hormone can be hydrolysed by breast tissues. The biological significance of these findings in vivo remains to be established.

  1. Sex dimorphism and depot differences in adipose tissue function.

    Science.gov (United States)

    White, Ursula A; Tchoukalova, Yourka D

    2014-03-01

    Obesity, characterized by excessive adiposity, is a risk factor for many metabolic pathologies, such as type 2 diabetes mellitus (T2DM). Numerous studies have shown that adipose tissue distribution may be a greater predictor of metabolic health. Upper-body fat (visceral and subcutaneous abdominal) is commonly associated with the unfavorable complications of obesity, while lower-body fat (gluteal-femoral) may be protective. Current research investigations are focused on analyzing the metabolic properties of adipose tissue, in order to better understand the mechanisms that regulate fat distribution in both men and women. This review will highlight the adipose tissue depot- and sex-dependent differences in white adipose tissue function, including adipogenesis, adipose tissue developmental patterning, the storage and release of fatty acids, and secretory function. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  2. Perivascular Adipose Tissue and Cardiometabolic Disease

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2013-04-01

    Full Text Available BACKGROUND: Obesity is associated with insulin resistance, hypertension, and cardiovascular disease, but the mechanisms underlying these associations are incompletely understood. Microvascular dysfunction may play an important role in the pathogenesis of both insulin resistance and hypertension in obesity. CONTENT: Perivascular adipose tissue (PVAT is a local deposit of adipose tissue surrounding the vasculature. PVAT is present throughout the body and has been shown to have a local effect on blood vessels. The influence of PVAT on the vasculature changes with increasing adiposity. PVAT similarly to other fat depots, is metabolically active, secreting a wide array of bioactive substances, termed ‘adipokines’. Adipokines include cytokines, chemokines and hormones that can act in a paracrine, autocrine or endocrine fashion. Many of the proinflammatory adipokines upregulated in obesity are known to influence vascular function, including endothelial function, oxidative stress, vascular stiffness and smooth muscle migration. Adipokines also stimulate immune cell migration into the vascular wall, potentially contributing to the inflammation found in atherosclerosis. Finally, adipokines modulate the effect of insulin on the vasculature, thereby decreasing insulin-mediated muscle glucose uptake. This leads to alterations in nitric oxide signaling, insulin resistance and potentially atherogenesis. SUMMARY: PVAT surrounds blood vessels. PVAT and the adventitial layer of blood vessels are in direct contact with each other. Healthy PVAT secretes adipokines and regulates vascular function. Obesity is associated with changes in adipokine secretion and the resultant inflammation of PVAT. The dysregulation of adipokines changes the effect of PVAT on the vasculature. Changes in perivascular adipokines secretion in obesity appear to contribute to the development of obesity-mediated vascular disease. KEYWORDS: obesity, perivascular adipose tissue, PVAT

  3. Organ-specific candidate biomarkers of inflammation found by comparative analyses of the human hepatic and adipose tissue transcriptome and secretome during LPS treatment

    NARCIS (Netherlands)

    Vonk, Roelf; Szalowska, Ewa; Dijkstra, Martijn L.; Weening, Desireé; de Vries, Marcel; Roelofsen, Han; Bruinenberg, Marcel; Hoek, Annemieke; Elferink, Maria; Groothuis, Genoveva

    2011-01-01

    Insulin resistance (IR) is accompanied by chronic low grade systemic inflammation and deregulation of total body energy homeostasis. We induced inflammation in human adipose and liver tissue in vitro in order to mimic inflammation in vivo with the aim to identify tissue-specific processes and biomar

  4. Pharmacological and nutritional agents promoting browning of white adipose tissue.

    Science.gov (United States)

    Bonet, M Luisa; Oliver, Paula; Palou, Andreu

    2013-05-01

    The role of brown adipose tissue in the regulation of energy balance and maintenance of body weight is well known in rodents. Recently, interest in this tissue has re-emerged due to the realization of active brown-like adipose tissue in adult humans and inducible brown-like adipocytes in white adipose tissue depots in response to appropriate stimuli ("browning process"). Brown-like adipocytes that appear in white fat depots have been called "brite" (from brown-in-white) or "beige" adipocytes and have characteristics similar to brown adipocytes, in particular the capacity for uncoupled respiration. There is controversy as to the origin of these brite/beige adipocytes, but regardless of this, induction of the browning of white fat represents an attractive potential strategy for the management and treatment of obesity and related complications. Here, the different physiological, pharmacological and dietary determinants that have been linked to white-to-brown fat remodeling and the molecular mechanisms involved are reviewed in detail. In the light of available data, interesting therapeutic perspectives can be expected from the use of specific drugs or food compounds able to induce a program of brown fat differentiation including uncoupling protein 1 expression and enhancing oxidative metabolism in white adipose cells. However, additional research is needed, mainly focused on the physiological relevance of browning and its dietary control, where the use of ferrets and other non-rodent animal models with a more similar adipose tissue organization and metabolism to humans could be of much help. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

  5. Skin Tissue Engineering: Application of Adipose-Derived Stem Cells

    Science.gov (United States)

    Zimoch, Jakub; Biedermann, Thomas

    2017-01-01

    Perception of the adipose tissue has changed dramatically over the last few decades. Identification of adipose-derived stem cells (ASCs) ultimately transformed paradigm of this tissue from a passive energy depot into a promising stem cell source with properties of self-renewal and multipotential differentiation. As compared to bone marrow-derived stem cells (BMSCs), ASCs are more easily accessible and their isolation yields higher amount of stem cells. Therefore, the ASCs are of high interest for stem cell-based therapies and skin tissue engineering. Currently, freshly isolated stromal vascular fraction (SVF), which may be used directly without any expansion, was also assessed to be highly effective in treating skin radiation injuries, burns, or nonhealing wounds such as diabetic ulcers. In this paper, we review the characteristics of SVF and ASCs and the efficacy of their treatment for skin injuries and disorders.

  6. Glycation and Hypoxia: Two Key Factors for Adipose Tissue Dysfunction.

    Science.gov (United States)

    Matafome, Paulo; Rodrigues, Tiago; Seica, Raquel

    2015-01-01

    Many aspects of adipose tissue pathophysiology in metabolic diseases have been described in the last years. One of such aspects is certainly hypoxia, which was shown to develop in adipose tissue of obese individuals and animal models. Recent data suggest two main factors for adipose tissue hypoxia: adipocyte hypertrophy and vascular dysfunction. In addition, glycation was also shown to induce morphological and functional alterations in adipose tissue. In particular, methylglyoxal directly formed from glucose was shown to potently induce AGE formation in vivo and to contribute to metabolic and vascular alterations in adipose tissue. Glycation and hypoxia are both thought to be on the basis of low grade inflammatory activation, further increasing metabolic dysregulation in adipose tissue. This review summarizes the current knowledge about the factors that contribute for tissue hypoxia and the role of glycation, not only at the vascular level, but also at the metabolic, oxidative and inflammatory levels.

  7. Stem cell treatment for patients with autoimmune disease by systemic infusion of culture-expanded autologous adipose tissue derived mesenchymal stem cells

    Directory of Open Access Journals (Sweden)

    Ra Jeong Chan

    2011-10-01

    Full Text Available Abstract Prolonged life expectancy, life style and environmental changes have caused a changing disease pattern in developed countries towards an increase of degenerative and autoimmune diseases. Stem cells have become a promising tool for their treatment by promoting tissue repair and protection from immune-attack associated damage. Patient-derived autologous stem cells present a safe option for this treatment since these will not induce immune rejection and thus multiple treatments are possible without any risk for allogenic sensitization, which may arise from allogenic stem cell transplantations. Here we report the outcome of treatments with culture expanded human adipose-derived mesenchymal stem cells (hAdMSCs of 10 patients with autoimmune associated tissue damage and exhausted therapeutic options, including autoimmune hearing loss, multiple sclerosis, polymyotitis, atopic dermatitis and rheumatoid arthritis. For treatment, we developed a standardized culture-expansion protocol for hAdMSCs from minimal amounts of fat tissue, providing sufficient number of cells for repetitive injections. High expansion efficiencies were routinely achieved from autoimmune patients and from elderly donors without measurable loss in safety profile, genetic stability, vitality and differentiation potency, migration and homing characteristics. Although the conclusions that can be drawn from the compassionate use treatments in terms of therapeutic efficacy are only preliminary, the data provide convincing evidence for safety and therapeutic properties of systemically administered AdMSC in human patients with no other treatment options. The authors believe that ex-vivo-expanded autologous AdMSCs provide a promising alternative for treating autoimmune diseases. Further clinical studies are needed that take into account the results obtained from case studies as those presented here.

  8. Adipose tissue angiogenesis: impact on obesity and type-2 diabetes.

    Science.gov (United States)

    Corvera, Silvia; Gealekman, Olga

    2014-03-01

    The growth and function of tissues are critically dependent on their vascularization. Adipose tissue is capable of expanding many-fold during adulthood, therefore requiring the formation of new vasculature to supply growing and proliferating adipocytes. The expansion of the vasculature in adipose tissue occurs through angiogenesis, where new blood vessels develop from those pre-existing within the tissue. Inappropriate angiogenesis may underlie adipose tissue dysfunction in obesity, which in turn increases type-2 diabetes risk. In addition, genetic and developmental factors involved in vascular patterning may define the size and expandability of diverse adipose tissue depots, which are also associated with type-2 diabetes risk. Moreover, the adipose tissue vasculature appears to be the niche for pre-adipocyte precursors, and factors that affect angiogenesis may directly impact the generation of new adipocytes. Here we review recent advances on the basic mechanisms of angiogenesis, and on the role of angiogenesis in adipose tissue development and obesity. A substantial amount of data points to a deficit in adipose tissue angiogenesis as a contributing factor to insulin resistance and metabolic disease in obesity. These emerging findings support the concept of the adipose tissue vasculature as a source of new targets for metabolic disease therapies. This article is part of a Special Issue entitled: Modulation of Adipose Tissue in Health and Disease.

  9. Effects of Ang II receptor blocker irbesartan on adipose tissue function in mice with metabolic disorders.

    Science.gov (United States)

    Maeda, Akinobu; Tamura, Kouichi; Wakui, Hiromichi; Ohsawa, Masato; Azushima, Kengo; Uneda, Kazushi; Kobayashi, Ryu; Tsurumi-Ikeya, Yuko; Kanaoka, Tomohiko; Dejima, Toru; Ohki, Koji; Haku, Sona; Yamashita, Akio; Umemura, Satoshi

    2014-01-01

    Recent studies indicate that the functional renin-angiotensin system (RAS) exists in the adipose tissue. The adipose tissue RAS is proposed in the pathophysiology of metabolic disorders. In the present study, we examined therapeutic effects of irbesartan, an angiotensin II (Ang II) type 1 receptor (AT1R)-specific blocker, in genetically obese diabetic KKAy mice, a model of human metabolic disorders without any dietary loading, with our focus on the analysis on possible effect of irbesartan on the adipose tissue. The treatment with irbesartan significantly lowered systolic blood pressure with a concomitant decrease in body weight in KKAy mice. In addition, irbesartan significantly decreased the adipose leptin mRNA expression and tended to decrease IL-6 mRNA expression in the adipose tissue of KKAy mice. Furthermore irbesartan preserved the adipose gene expression of AT1R-associated protein (ATRAP), an endogenous inhibitory molecule of tissue AT1R signaling, with a concomitant tendency of up-regulation of adipose tissue ATRAP/AT1R ratio. Collectively, these results suggest that the irbesartan-induced beneficial suppressive effect on the leptin-IL-6 axis in the adipose tissue in KKAy mice is partly mediated by a trend of up-regulation of the adipose ATRAP/AT1R ratio as one of pleiotropic effects of irbesartan.

  10. The potential roles for adipose tissue in peripheral nerve regeneration.

    Science.gov (United States)

    Walocko, Frances M; Khouri, Roger K; Urbanchek, Melanie G; Levi, Benjamin; Cederna, Paul S

    2016-01-01

    This review summarizes current understanding about the role of adipose-derived tissues in peripheral nerve regeneration and discusses potential advances that would translate this approach into the clinic. We searched PubMed for in vivo, experimental studies on the regenerative effects of adipose-derived tissues on peripheral nerve injuries. We summarized the methods and results for the 42 experiments. Adipose-derived tissues enhanced peripheral nerve regeneration in 86% of the experiments. Ninety-five percent evaluated purified, cultured, or differentiated adipose tissue. These approaches have regulatory and scaling burdens, restricting clinical usage. Only one experiment tested the ability of adipose tissue to enhance nerve regeneration in conjunction with nerve autografts, the clinical gold standard. Scientific studies illustrate that adipose-derived tissues enhance regeneration of peripheral nerves. Before this approach achieves clinical acceptance, fat processing must become automated and regulatory approval achieved. Animal studies using whole fat grafts are greatly needed for clinical translation. © 2015 Wiley Periodicals, Inc.

  11. Adipose tissue and its role in organ crosstalk.

    Science.gov (United States)

    Romacho, T; Elsen, M; Röhrborn, D; Eckel, J

    2014-04-01

    The discovery of adipokines has revealed adipose tissue as a central node in the interorgan crosstalk network, which mediates the regulation of multiple organs and tissues. Adipose tissue is a true endocrine organ that produces and secretes a wide range of mediators regulating adipose tissue function in an auto-/paracrine manner and important distant targets, such as the liver, skeletal muscle, the pancreas and the cardiovascular system. In metabolic disorders such as obesity, enlargement of adipocytes leads to adipose tissue dysfunction and a shift in the secretory profile with an increased release of pro-inflammatory adipokines. Adipose tissue dysfunction has a central role in the development of insulin resistance, type 2 diabetes, and cardiovascular diseases. Besides the well-acknowledged role of adipokines in metabolic diseases, and the increasing number of adipokines being discovered in the last years, the mechanisms underlying the release of many adipokines from adipose tissue remain largely unknown. To combat metabolic diseases, it is crucial to better understand how adipokines can modulate adipose tissue growth and function. Therefore, we will focus on adipokines with a prominent role in auto-/paracrine crosstalk within the adipose tissue such as RBP4, HO-1, WISP2, SFRPs and chemerin. To depict the endocrine crosstalk between adipose tissue with skeletal muscle, the cardiovascular system and the pancreas, we will report the main findings regarding the direct effects of adiponectin, leptin, DPP4 and visfatin on skeletal muscle insulin resistance, cardiovascular function and β-cell growth and function.

  12. Microarray Evidences the Role of Pathologic Adipose Tissue in Insulin Resistance and Their Clinical Implications

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    Sandeep Kumar Mathur

    2011-01-01

    Full Text Available Clustering of insulin resistance and dysmetabolism with obesity is attributed to pathologic adipose tissue. The morphologic hallmarks of this pathology are adipocye hypertrophy and heightened inflammation. However, it's underlying molecular mechanisms remains unknown. Study of gene function in metabolically active tissues like adipose tissue, skeletal muscle and liver is a promising strategy. Microarray is a powerful technique of assessment of gene function by measuring transcription of large number of genes in an array. This technique has several potential applications in understanding pathologic adipose tissue. They are: (1 transcriptomic differences between various depots of adipose tissue, adipose tissue from obese versus lean individuals, high insulin resistant versus low insulin resistance, brown versus white adipose tissue, (2 transcriptomic profiles of various stages of adipogenesis, (3 effect of diet, cytokines, adipokines, hormones, environmental toxins and drugs on transcriptomic profiles, (4 influence of adipokines on transcriptomic profiles in skeletal muscle, hepatocyte, adipose tissue etc., and (5 genetics of gene expression. The microarray evidences of molecular basis of obesity and insulin resistance are presented here. Despite the limitations, microarray has potential clinical applications in finding new molecular targets for treatment of insulin resistance and classification of adipose tissue based on future risk of insulin resistance syndrome.

  13. Bone Marrow Adipose Tissue: To Be or Not To Be a Typical Adipose Tissue?

    Science.gov (United States)

    Hardouin, Pierre; Rharass, Tareck; Lucas, Stéphanie

    2016-01-01

    Bone marrow adipose tissue (BMAT) emerges as a distinct fat depot whose importance has been proved in the bone-fat interaction. Indeed, it is well recognized that adipokines and free fatty acids released by adipocytes can directly or indirectly interfere with cells of bone remodeling or hematopoiesis. In pathological states, such as osteoporosis, each of adipose tissues - subcutaneous white adipose tissue (WAT), visceral WAT, brown adipose tissue (BAT), and BMAT - is differently associated with bone mineral density (BMD) variations. However, compared with the other fat depots, BMAT displays striking features that makes it a substantial actor in bone alterations. BMAT quantity is well associated with BMD loss in aging, menopause, and other metabolic conditions, such as anorexia nervosa. Consequently, BMAT is sensed as a relevant marker of a compromised bone integrity. However, analyses of BMAT development in metabolic diseases (obesity and diabetes) are scarce and should be, thus, more systematically addressed to better apprehend the bone modifications in that pathophysiological contexts. Moreover, bone marrow (BM) adipogenesis occurs throughout the whole life at different rates. Following an ordered spatiotemporal expansion, BMAT has turned to be a heterogeneous fat depot whose adipocytes diverge in their phenotype and their response to stimuli according to their location in bone and BM. In vitro, in vivo, and clinical studies point to a detrimental role of BM adipocytes (BMAs) throughout the release of paracrine factors that modulate osteoblast and/or osteoclast formation and function. However, the anatomical dissemination and the difficulties to access BMAs still hamper our understanding of the relative contribution of BMAT secretions compared with those of peripheral adipose tissues. A further characterization of the phenotype and the functional regulation of BMAs are ever more required. Based on currently available data and comparison with other fat tissues

  14. Obesity induces a phenotypic switch in adipose tissue macrophage polarization

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    Lumeng, Carey N.; Bodzin, Jennifer L.; Alan R Saltiel

    2007-01-01

    Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80+CD11c+ population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or “alternatively activated” macrophages, i...

  15. FGF receptor antagonism does not affect adipose tissue development in nutritionally induced obesity.

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    Scroyen, Ilse; Vranckx, Christine; Lijnen, Henri Roger

    2014-01-01

    The fibroblast growth factor (FGF)-FGF receptor (FGFR) system plays a role in angiogenesis and maintenance of vascular integrity, but its potential role in adipose tissue related angiogenesis and development is still unknown. Administration of SSR, a low molecular weight inhibitor of multiple FGFRs, did not significantly affect body weight nor weight of subcutaneous or gonadal (GON) fat, as compared with pair-fed control mice. Adipocyte hypertrophy and reduced adipocyte density were only observed in GON adipose tissues of treated mice. Adipose tissue angiogenesis was not affected by SSR treatment, as normalized blood vessel density was comparable in adipose tissues of both groups. Blocking the FGF-FGFR system in vivo does not markedly affect adipose tissue development in mice with nutritionally induced obesity.

  16. Exercise Regulation of Marrow Adipose Tissue

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    Pagnotti, Gabriel M.; Styner, Maya

    2016-01-01

    Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT) remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell (MSC) pool that also gives rise to osteoblasts, chondrocytes, and myocytes, among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here, we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions, and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally supportive tissues, inhibits bone resorption, and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high-fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone – a PPARγ-agonist known to increase MAT and fracture risk – mice demonstrate a fivefold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  17. Exercise Regulation of Marrow Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Gabriel M Pagnotti

    2016-07-01

    Full Text Available Despite association with low bone density and skeletal fractures, marrow adipose tissue (MAT remains poorly understood. The marrow adipocyte originates from the mesenchymal stem cell pool (MSC that gives rise also to osteoblasts, chondrocytes, and myocytes among other cell types. To date, the presence of MAT has been attributed to preferential biasing of MSC into the adipocyte rather than osteoblast lineage, thus negatively impacting bone formation. Here we focus on understanding the physiology of MAT in the setting of exercise, dietary interventions and pharmacologic agents that alter fat metabolism. The beneficial effect of exercise on musculoskeletal strength is known: exercise induces bone formation, encourages growth of skeletally-supportive tissues, inhibits bone resorption and alters skeletal architecture through direct and indirect effects on a multiplicity of cells involved in skeletal adaptation. MAT is less well studied due to the lack of reproducible quantification techniques. In recent work, osmium-based 3D quantification shows a robust response of MAT to both dietary and exercise intervention in that MAT is elevated in response to high fat diet and can be suppressed following daily exercise. Exercise-induced bone formation correlates with suppression of MAT, such that exercise effects might be due to either calorie expenditure from this depot, or from mechanical biasing of MSC lineage away from fat and toward bone, or a combination thereof. Following treatment with the anti-diabetes drug rosiglitazone - a PPARγ-agonist known to increase MAT and fracture risk - mice demonstrate a 5-fold higher femur MAT volume compared to the controls. In addition to preventing MAT accumulation in control mice, exercise intervention significantly lowers MAT accumulation in rosiglitazone-treated mice. Importantly, exercise induction of trabecular bone volume is unhindered by rosiglitazone. Thus, despite rosiglitazone augmentation of MAT, exercise

  18. Browning effects of (-)-epicatechin on adipocytes and white adipose tissue.

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    Varela, Claudia Elena; Rodriguez, Alonso; Romero-Valdovinos, Mirza; Mendoza-Lorenzo, Patricia; Mansour, Christina; Ceballos, Guillermo; Villarreal, Francisco; Ramirez-Sanchez, Israel

    2017-09-15

    In this study, we demonstrate that (-)-epicatechin (Epi), a cacao flavanol, induces the browning of fat by promoting mitochondrial biogenesis, enhancing indicators of mitochondrial structure and function, increasing fatty acid metabolism and upregulating the expression of brown adipose tissue-specific proteins in a high-fat diet mouse model of obesity and in cultured human adipocytes. Epi treatment significantly improved mitochondrial function, as measured by citrate synthase activity, and also reduced protein acetylation of total and specific regulators in both adipose tissue and human adipocytes. Browning of fat via Epi was evidenced by the increased expression of key thermogenic genes, phosphorylation of upstream regulators of fatty acid oxidation, and reduced triglyceride levels. Properly designed clinical trials are needed to explore the potential of Epi as an agent that promotes the browning of fat. Copyright © 2017. Published by Elsevier B.V.

  19. Heterogeneity of white adipose tissue: molecular basis and clinical implications.

    Science.gov (United States)

    Kwok, Kelvin H M; Lam, Karen S L; Xu, Aimin

    2016-03-11

    Adipose tissue is a highly heterogeneous endocrine organ. The heterogeneity among different anatomical depots stems from their intrinsic differences in cellular and physiological properties, including developmental origin, adipogenic and proliferative capacity, glucose and lipid metabolism, insulin sensitivity, hormonal control, thermogenic ability and vascularization. Additional factors that influence adipose tissue heterogeneity are genetic predisposition, environment, gender and age. Under obese condition, these depot-specific differences translate into specific fat distribution patterns, which are closely associated with differential cardiometabolic risks. For instance, individuals with central obesity are more susceptible to developing diabetes and cardiovascular complications, whereas those with peripheral obesity are more metabolically healthy. This review summarizes the clinical and mechanistic evidence for the depot-specific differences that give rise to different metabolic consequences, and provides therapeutic insights for targeted treatment of obesity.

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

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    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.

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

    Science.gov (United States)

    Park, Byung Young; Lee, Hyunghee; Woo, Sangee; Yoon, Miso; Kim, Jeongjun; Hong, Yeonhee; Lee, Hee Suk; Park, Eun Kyu; Hahm, Jong Cheon; Kim, Jin Woo; Shin, Soon Shik; Kim, Min-Young; Yoon, Michung

    2015-01-01

    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.

  2. Adipose tissue inflammation: a cause or consequence of obesity-related insulin resistance?

    Science.gov (United States)

    Blüher, Matthias

    2016-09-01

    The worldwide obesity epidemic has become a major health concern, because it contributes to higher mortality due to an increased risk for noncommunicable diseases including cardiovascular diseases, type 2 diabetes, musculoskeletal disorders and some cancers. Insulin resistance may link accumulation of adipose tissue in obesity to metabolic diseases, although the underlying mechanisms are not completely understood. In the past decades, data from human studies and transgenic animal models strongly suggested correlative, but also causative associations between activation of proinflammatory pathways and insulin resistance. Particularly chronic inflammation in adipose tissue seems to play an important role in the development of obesity-related insulin resistance. On the other hand, adipose tissue inflammation has been shown to be essential for healthy adipose tissue expansion and remodelling. However, whether adipose tissue inflammation represents a consequence or a cause of impaired insulin sensitivity remains an open question. A better understanding of the molecular pathways linking excess adipose tissue storage to chronic inflammation and insulin resistance may provide the basis for the future development of anti-inflammatory treatment strategies to improve adverse metabolic consequences of obesity. In this review, potential mechanisms of adipose tissue inflammation and how adipose tissue inflammation may cause insulin resistance are discussed. © 2016 The Author(s). published by Portland Press Limited on behalf of the Biochemical Society.

  3. Brown adipose tissue in cetacean blubber.

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    Osamu Hashimoto

    Full Text Available Brown adipose tissue (BAT plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1, within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool

  4. Brown adipose tissue in cetacean blubber.

    Science.gov (United States)

    Hashimoto, Osamu; Ohtsuki, Hirofumi; Kakizaki, Takehiko; Amou, Kento; Sato, Ryo; Doi, Satoru; Kobayashi, Sara; Matsuda, Ayaka; Sugiyama, Makoto; Funaba, Masayuki; Matsuishi, Takashi; Terasawa, Fumio; Shindo, Junji; Endo, Hideki

    2015-01-01

    Brown adipose tissue (BAT) plays an important role in thermoregulation in species living in cold environments, given heat can be generated from its chemical energy reserves. Here we investigate the existence of BAT in blubber in four species of delphinoid cetacean, the Pacific white-sided and bottlenose dolphins, Lagenorhynchus obliquidens and Tursiops truncates, and Dall's and harbour porpoises, Phocoenoides dalli and Phocoena phocoena. Histology revealed adipocytes with small unilocular fat droplets and a large eosinophilic cytoplasm intermingled with connective tissue in the innermost layers of blubber. Chemistry revealed a brown adipocyte-specific mitochondrial protein, uncoupling protein 1 (UCP1), within these same adipocytes, but not those distributed elsewhere throughout the blubber. Western blot analysis of extracts from the inner blubber layer confirmed that the immunohistochemical positive reaction was specific to UCP1 and that this adipose tissue was BAT. To better understand the distribution of BAT throughout the entire cetacean body, cadavers were subjected to computed tomography (CT) scanning. Resulting imagery, coupled with histological corroboration of fine tissue structure, revealed adipocytes intermingled with connective tissue in the lowest layer of blubber were distributed within a thin, highly dense layer that extended the length of the body, with the exception of the rostrum, fin and fluke regions. As such, we describe BAT effectively enveloping the cetacean body. Our results suggest that delphinoid blubber could serve a role additional to those frequently attributed to it: simple insulation blanket, energy storage, hydrodynamic streamlining or contributor to positive buoyancy. We believe delphinoid BAT might also function like an electric blanket, enabling animals to frequent waters cooler than blubber as an insulator alone might otherwise allow an animal to withstand, or allow animals to maintain body temperature in cool waters during

  5. Brain-adipose tissue neural crosstalk.

    Science.gov (United States)

    Bartness, Timothy J; Song, C Kay

    2007-07-24

    The preponderance of basic obesity research focuses on its development as affected by diet and other environmental factors, genetics and their interactions. By contrast, we have been studying the reversal of a naturally-occurring seasonal obesity in Siberian hamsters. In the course of this work, we determined that the sympathetic innervation of white adipose tissue (WAT) is the principal initiator of lipid mobilization not only in these animals, but in all mammals including humans. We present irrefutable evidence for the sympathetic nervous system (SNS) innervation of WAT with respect to neuroanatomy (including its central origins as revealed by transneuronal viral tract tracers), neurochemistry (norepinephrine turnover studies) and function (surgical and chemical denervation). A relatively unappreciated role of WAT SNS innervation also is reviewed--the control of fat cell proliferation as shown by selective chemical denervation that triggers adipocyte proliferation, although the precise mechanism by which this occurs presently is unknown. There is no, however, equally strong evidence for the parasympathetic innervation of this tissue; indeed, the data largely are negative severely questioning its existence and importance. Convincing evidence also is given for the sensory innervation of WAT (as shown by tract tracing and by markers for sensory nerves in WAT), with suggestive data supporting a possible role in conveying information on the degree of adiposity to the brain. Collectively, these data offer an additional or alternative view to the predominate one of the control of body fat stores via circulating factors that serve as efferent and afferent communicators.

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

    Science.gov (United States)

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

    2017-03-01

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

  7. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation.

    Science.gov (United States)

    Huang, Zhi H; Reardon, Catherine A; Getz, Godfrey S; Maeda, Nobuyo; Mazzone, Theodore

    2015-02-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state.

  8. Selective suppression of adipose tissue apoE expression impacts systemic metabolic phenotype and adipose tissue inflammation

    Science.gov (United States)

    Huang, Zhi H.; Reardon, Catherine A.; Getz, Godfrey S.; Maeda, Nobuyo; Mazzone, Theodore

    2015-01-01

    apoE is a multi-functional protein expressed in several cell types and in several organs. It is highly expressed in adipose tissue, where it is important for modulating adipocyte lipid flux and gene expression in isolated adipocytes. In order to investigate a potential systemic role for apoE that is produced in adipose tissue, mice were generated with selective suppression of adipose tissue apoE expression and normal circulating apoE levels. These mice had less adipose tissue with smaller adipocytes containing fewer lipids, but no change in adipocyte number compared with control mice. Adipocyte TG synthesis in the presence of apoE-containing VLDL was markedly impaired. Adipocyte caveolin and leptin gene expression were reduced, but adiponectin, PGC-1, and CPT-1 gene expression were increased. Mice with selective suppression of adipose tissue apoE had lower fasting lipid, insulin, and glucose levels, and glucose and insulin tolerance tests were consistent with increased insulin sensitivity. Lipid storage in muscle, heart, and liver was significantly reduced. Adipose tissue macrophage inflammatory activation was markedly diminished with suppression of adipose tissue apoE expression. Our results establish a novel effect of adipose tissue apoE expression, distinct from circulating apoE, on systemic substrate metabolism and adipose tissue inflammatory state. PMID:25421060

  9. Macrophage elastase suppresses white adipose tissue expansion with cigarette smoking.

    Science.gov (United States)

    Tsuji, Takao; Kelly, Neil J; Takahashi, Saeko; Leme, Adriana S; Houghton, A McGarry; Shapiro, Steven D

    2014-12-01

    Macrophage elastase (MMP12) is a key mediator of cigarette smoke (CS)-induced emphysema, yet its role in other smoking related pathologies remains unclear. The weight suppressing effects of smoking are a major hindrance to cessation efforts, and MMP12 is known to suppress the vascularization on which adipose tissue growth depends by catalyzing the formation of antiangiogenic peptides endostatin and angiostatin. The goal of this study was to determine the role of MMP12 in adipose tissue growth and smoking-related suppression of weight gain. Whole body weights and white adipose depots from wild-type and Mmp12-deficient mice were collected during early postnatal development and after chronic CS exposure. Adipose tissue specimens were analyzed for angiogenic and adipocytic markers and for content of the antiangiogenic peptides endostatin and angiostatin. Cultured 3T3-L1 adipocytes were treated with adipose tissue homogenate to examine its effects on vascular endothelial growth factor (VEGF) expression and secretion. MMP12 content and activity were increased in the adipose tissue of wild-type mice at 2 weeks of age, leading to elevated endostatin production, inhibition of VEGF secretion, and decreased adipose tissue vascularity. By 8 weeks of age, adipose MMP12 levels subsided, and the protein was no longer detectable. However, chronic CS exposure led to macrophage accumulation and restored adipose MMP12 activity, thereby suppressing adipose tissue mass and vascularity. Our results reveal a novel systemic role for MMP12 in postnatal adipose tissue expansion and smoking-associated weight loss by suppressing vascularity within the white adipose tissue depots.

  10. Adipokines and the Endocrine Role of Adipose Tissues.

    Science.gov (United States)

    Giralt, Marta; Cereijo, Rubén; Villarroya, Francesc

    2016-01-01

    The last two decades have witnessed a shift in the consideration of white adipose tissue as a mere repository of fat to be used when food becomes scarce to a true endocrine tissue releasing regulatory signals, the so-called adipokines, to the whole body. The control of eating behavior, the peripheral insulin sensitivity, and even the development of the female reproductive system are among the physiological events controlled by adipokines. Recently, the role of brown adipose tissue in human physiology has been recognized. The metabolic role of brown adipose tissue is opposite to white fat; instead of storing fat, brown adipose tissue is a site of energy expenditure via adaptive thermogenesis. There is growing evidence that brown adipose tissue may have its own pattern of secreted hormonal factors, the so-called brown adipokines, having distinctive biological actions on the overall physiological adaptations to enhance energy expenditure.

  11. Brown Adipose Tissue: A New Target for Antiobesity Therapy

    Directory of Open Access Journals (Sweden)

    Anna Meiliana

    2010-08-01

    Full Text Available BACKGROUND: Human fat consist of white and brown adipose tissue (WAT and BAT. Though most fat is energy-storing WAT, the thermogenic capacity of even small amounts of BAT makes it an attractive therapeutic target for inducing weight loss through energy expenditure. CONTENT: Over the past year, several independent research teams used a combination of positron-emission tomography and computed tomography (PET/CT imaging, immunohistochemistry and gene and protein expression assays to prove conclusively that adult humans have functional BAT. BAT is important for thermogenesis and energy balance in small mammals and its induction in mice promotes energy expenditure, reduces adiposity and protects mice from diet-induced obesity. The thermogenic capacity of BAT is impressive. In humans, it has been estimated that as little as 50g of BAT could utilize up to 20% of basal caloric needs if maximally stimulated. SUMMARY: The obesity pandemic requires new and novel treatments. The past few years have witnessed multiple studies conclusively showing that adult humans have functional BAT, a tissue that has a tremendous capacity for obesity-reducing thermogenesis. Novel therapies targeting BAT thermogenesis may be available in the near future as therapeutic options for obesity and diabetes. Thermogenic ingredients may be considered as functional agents that could help in preventing a positive energy balance and obesity. KEYWORDS: brown adipose tissue, thermogenesis, energy expenditure, antiobesity therapy.

  12. Brain–gut–adipose-tissue communication pathways at a glance

    Directory of Open Access Journals (Sweden)

    Chun-Xia Yi

    2012-09-01

    Full Text Available One of the ‘side effects’ of our modern lifestyle is a range of metabolic diseases: the incidence of obesity, type 2 diabetes and associated cardiovascular diseases has grown to pandemic proportions. This increase, which shows no sign of reversing course, has occurred despite education and new treatment options, and is largely due to a lack of knowledge about the precise pathology and etiology of metabolic disorders. Accumulating evidence suggests that the communication pathways linking the brain, gut and adipose tissue might be promising intervention points for metabolic disorders. To maintain energy homeostasis, the brain must tightly monitor the peripheral energy state. This monitoring is also extremely important for the brain’s survival, because the brain does not store energy but depends solely on a continuous supply of nutrients from the general circulation. Two major groups of metabolic inputs inform the brain about the peripheral energy state: short-term signals produced by the gut system and long-term signals produced by adipose tissue. After central integration of these inputs, the brain generates neuronal and hormonal outputs to balance energy intake with expenditure. Miscommunication between the gut, brain and adipose tissue, or the degradation of input signals once inside the brain, lead to the brain misunderstanding the peripheral energy state. Under certain circumstances, the brain responds to this miscommunication by increasing energy intake and production, eventually causing metabolic disorders. This poster article overviews current knowledge about communication pathways between the brain, gut and adipose tissue, and discusses potential research directions that might lead to a better understanding of the mechanisms underlying metabolic disorders.

  13. Implication of low level inflammation in the insulin resistance of adipose tissue at late pregnancy.

    Science.gov (United States)

    de Castro, J; Sevillano, J; Marciniak, J; Rodriguez, R; González-Martín, C; Viana, M; Eun-suk, O H; de Mouzon, S Hauguel; Herrera, E; Ramos, M P

    2011-11-01

    Insulin resistance is a characteristic of late pregnancy, and adipose tissue is one of the tissues that most actively contributes to the reduced maternal insulin sensitivity. There is evidence that pregnancy is a condition of moderate inflammation, although the physiological role of this low-grade inflammation remains unclear. The present study was designed to validate whether low-grade inflammation plays a role in the development of insulin resistance in adipose tissue during late pregnancy. To this end, we analyzed proinflammatory adipokines and kinases in lumbar adipose tissue of nonpregnant and late pregnant rats at d 18 and 20 of gestation. We found that circulating and tissue levels of adipokines, such as IL-1β, plasminogen activator inhibitor-1, and TNF-α, were increased at late pregnancy, which correlated with insulin resistance. The observed increase in adipokines coincided with an enhanced activation of p38 MAPK in adipose tissue. Treatment of pregnant rats with the p38 MAPK inhibitor SB 202190 increased insulin-stimulated tyrosine phosphorylation of the insulin receptor (IR) and IR substrate-1 in adipose tissue, which was paralleled by a reduction of IR substrate-1 serine phosphorylation and an enhancement of the metabolic actions of insulin. These results indicate that activation of p38 MAPK in adipose tissue contributes to adipose tissue insulin resistance at late pregnancy. Furthermore, the results of the present study support the hypothesis that physiological low-grade inflammation in the maternal organism is relevant to the development of pregnancy-associated insulin resistance.

  14. Comparison of different fabrication techniques for human adipose tissue engineering in severe combined immunodeficient mice.

    Science.gov (United States)

    Frerich, Bernhard; Winter, Karsten; Scheller, Konstanze; Braumann, Ulf-Dietrich

    2012-03-01

    Adipose tissue engineering has been advocated for soft-tissue augmentation and for the treatment of soft tissue defects. The efficacy in terms of persistence of the engineered fat is, however, not yet understood and could depend on the nature of fabrication and application. The high metabolic demand of adipose tissue also points to the problem of vascularization. Endothelial cell (EC) cotransplantation could be a solution. Human adipose tissue-derived stromal cells were seeded on collagen microcarriers and submitted to adipogenic differentiation ("microparticles"). In a first run of experiments, these microparticles were implanted under the skin of severe combined immunodeficient (SCID) mice (n = 45) with and without the addition of human umbilical vein ECs (HUVECs). A group of carriers without any cells served as control. In a second run, adipose tissue constructs were fabricated by embedding microparticles in fibrin matrix with and without the addition of HUVEC, and were also implanted in SCID mice (n = 30). The mice were sacrificed after 12 days, 4 weeks, and 4 months. Mature adipose tissue, fibrous tissue, and acellular regions were quantified on whole-specimen histological sections. The implantation of microparticles showed a better sustainment of tissue volume and a higher degree of mature adipose tissue compared with adipose tissue constructs. Immunohistology proved obviously perfused human tissue-engineered vessels. There was a limited but not significant advantage in EC cotransplantation after 4 weeks in terms of tissue volume. In groups with EC cotransplantation, there were significantly fewer acellular/necrotic areas after 4 weeks and 4 months. In conclusion, the size of the implanted tissue equivalents is a crucial parameter, affecting volume maintenance and the gain of mature adipose tissue. EC cotransplantation leads to functional stable vascular networks connecting in part to the host vasculature and contributing to tissue perfusion; however

  15. Berberine activates thermogenesis in white and brown adipose tissue.

    Science.gov (United States)

    Zhang, Zhiguo; Zhang, Huizhi; Li, Bo; Meng, Xiangjian; Wang, Jiqiu; Zhang, Yifei; Yao, Shuangshuang; Ma, Qinyun; Jin, Lina; Yang, Jian; Wang, Weiqing; Ning, Guang

    2014-11-25

    Obesity develops when energy intake exceeds energy expenditure. Promoting brown adipose tissue formation and function increases energy expenditure and hence may counteract obesity. Berberine (BBR) is a compound derived from the Chinese medicinal plant Coptis chinensis. Here we show that BBR increases energy expenditure, limits weight gain, improves cold tolerance and enhances brown adipose tissue (BAT) activity in obese db/db mice. BBR markedly induces the development of brown-like adipocytes in inguinal, but not epididymal adipose depots. BBR also increases expression of UCP1 and other thermogenic genes in white and BAT and primary adipocytes via a mechanism involving AMPK and PGC-1α. BBR treatment also inhibits AMPK activity in the hypothalamus, but genetic activation of AMPK in the ventromedial nucleus of the hypothalamus does not prevent BBR-induced weight loss and activation of the thermogenic programme. Our findings establish a role for BBR in regulating organismal energy balance, which may have potential therapeutic implications for the treatment of obesity.

  16. Cell supermarket: Adipose tissue as a source of stem cells

    Science.gov (United States)

    Adipose tissue is derived from numerous sources, and in recent years has been shown to provide numerous cells from what seemingly was a population of homogeneous adipocytes. Considering the types of cells that adipose tissue-derived cells may form, these cells may be useful in a variety of clinical ...

  17. Reduced adipose tissue lymphatic drainage of macromolecules in obese subjects

    DEFF Research Database (Denmark)

    Arngrim, N; Simonsen, L; Holst, Jens Juul

    2012-01-01

    The aim of this study was to investigate subcutaneous adipose tissue lymphatic drainage (ATLD) of macromolecules in lean and obese subjects and, furthermore, to evaluate whether ATLD may change in parallel with adipose tissue blood flow. Lean and obese male subjects were studied before and after ...... online publication, 3 July 2012; doi:10.1038/ijo.2012.98....

  18. Adipose tissue macrophages: going off track during obesity

    NARCIS (Netherlands)

    Boutens, L.; Stienstra, R.

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically

  19. Local and systemic effects of visceral and perivascular adipose tissue

    NARCIS (Netherlands)

    Verhagen, S.N.

    2012-01-01

    Rather than being solely a storage depot for triglycerides, adipose tissue is able to secrete pro- and anti-inflammatory cytokines and adipokines. A state of low grade inflammation associated with excess adipose tissue is involved in the increase in the incidences of atherosclerotic diseases and

  20. Adipose tissue macrophages: going off track during obesity

    NARCIS (Netherlands)

    Boutens, L.; Stienstra, R.

    2016-01-01

    Inflammation originating from the adipose tissue is considered to be one of the main driving forces for the development of insulin resistance and type 2 diabetes in obese individuals. Although a plethora of different immune cells shapes adipose tissue inflammation, this review is specifically focuse

  1. Relations between antioxidant vitamins in adipose tissue, plasma, and diet

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Veer, P. van 't; Brants, H.A.M.; Berg, H. van den; Schoonhoven, J. van; Hermus, R.J.J.

    1995-01-01

    For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of β-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of β-carotene, retinol, an

  2. Characterization of the human visceral adipose tissue secretome

    NARCIS (Netherlands)

    Alvarez Llamas, Gloria; Szalowska, Ewa; de Vries, Marcel P.; Weening, Desiree; Landman, Karloes; Hoek, Annemieke; Wolffenbuttel, Bruce H. R.; Roelofsen, Johan; Vonk, Roel J.

    2007-01-01

    Adipose tissue is an endocrine organ involved in storage and release of energy but also in regulation of energy metabolism in other organs via secretion of peptide and protein hormones (adipokines). Especially visceral adipose tissue has been implicated in the development of metabolic syndrome and t

  3. Involvement of mast cells in adipose tissue fibrosis.

    Science.gov (United States)

    Hirai, Shizuka; Ohyane, Chie; Kim, Young-Il; Lin, Shan; Goto, Tsuyoshi; Takahashi, Nobuyuki; Kim, Chu-Sook; Kang, Jihey; Yu, Rina; Kawada, Teruo

    2014-02-01

    Recently, fibrosis is observed in obese adipose tissue; however, the pathogenesis remains to be clarified. Obese adipose tissue is characterized by chronic inflammation with massive accumulation of immune cells including mast cells. The objective of the present study was to clarify the relationship between fibrosis and mast cells in obese adipose tissue, as well as to determine the origin of infiltrating mast cells. We observed the enhancement of mast cell accumulation and fibrosis in adipose tissue of severely obese diabetic db/db mice. Furthermore, adipose tissue-conditioned medium (ATCM) from severely obese diabetic db/db mice significantly enhanced collagen 5 mRNA expression in NIH-3T3 fibroblasts, and this enhancement was suppressed by the addition of an anti-mast cell protease 6 (MCP-6) antibody. An in vitro study showed that only collagen V among various types of collagen inhibited preadipocyte differentiation. Moreover, we found that ATCM from the nonobese but not obese stages of db/db mice significantly enhanced the migration of bone marrow-derived mast cells (BMMCs). These findings suggest that immature mast cells that infiltrate into adipose tissue at the nonobese stage gradually mature with the progression of obesity and diabetes and that MCP-6 secreted from mature mast cells induces collagen V expression in obese adipose tissue, which may contribute to the process of adipose tissue fibrosis. Induction of collagen V by MCP-6 might accelerate insulin resistance via the suppression of preadipocyte differentiation.

  4. Local and systemic effects of visceral and perivascular adipose tissue

    NARCIS (Netherlands)

    Verhagen, S.N.

    2012-01-01

    Rather than being solely a storage depot for triglycerides, adipose tissue is able to secrete pro- and anti-inflammatory cytokines and adipokines. A state of low grade inflammation associated with excess adipose tissue is involved in the increase in the incidences of atherosclerotic diseases and typ

  5. Characterization of the human visceral adipose tissue secretome

    NARCIS (Netherlands)

    Alvarez Llamas, Gloria; Szalowska, Ewa; de Vries, Marcel P.; Weening, Desiree; Landman, Karloes; Hoek, Annemieke; Wolffenbuttel, Bruce H. R.; Roelofsen, Johan; Vonk, Roel J.

    2007-01-01

    Adipose tissue is an endocrine organ involved in storage and release of energy but also in regulation of energy metabolism in other organs via secretion of peptide and protein hormones (adipokines). Especially visceral adipose tissue has been implicated in the development of metabolic syndrome and t

  6. Mechanisms of inflammatory responses in obese adipose tissue

    NARCIS (Netherlands)

    Sun, S.Y.; Yewei, Ji; Kersten, A.H.; Qi, L.

    2012-01-01

    The fields of immunology and metabolism are rapidly converging on adipose tissue. During obesity, many immune cells infiltrate or populate in adipose tissue and promote a low-grade chronic inflammation. Studies to date have suggested that perturbation of inflammation is critically linked to nutrient

  7. Relations between antioxidant vitamins in adipose tissue, plasma, and diet

    NARCIS (Netherlands)

    Kardinaal, A.F.M.; Veer, P. van 't; Brants, H.A.M.; Berg, H. van den; Schoonhoven, J. van; Hermus, R.J.J.

    1995-01-01

    For an evaluation of fat-soluble vitamin concentrations in adipose tissue as biomarkers of intake, estimates of usual intake of β-carotene, total vitamin A, and vitamin E (assessed by food frequency questionnaire) were compared with plasma and adipose tissue concentrations of β-carotene, retinol, an

  8. A hot interaction between immune cells and adipose tissue

    NARCIS (Netherlands)

    van den Berg, S.M.

    2017-01-01

    Systemic as well as adipose tissue inflammation contributes to the development of obesity-associated diseases. This thesis describes three targets to battle this chronic inflammation in a model of diet-induced obesity in mice. First, we studied inflammation in obese white - and brown adipose tissue

  9. Altered autophagy in human adipose tissues in obesity

    Science.gov (United States)

    Context: Autophagy is a housekeeping mechanism, involved in metabolic regulation and stress response, shown recently to regulate lipid droplets biogenesis/breakdown and adipose tissue phenotype. Objective: We hypothesized that in human obesity autophagy may be altered in adipose tissue in a fat d...

  10. The role of adipose tissue in cancer-associated cachexia.

    Science.gov (United States)

    Vaitkus, Janina A; Celi, Francesco S

    2017-03-01

    Adipose tissue (fat) is a heterogeneous organ, both in function and histology, distributed throughout the body. White adipose tissue, responsible for energy storage and more recently found to have endocrine and inflammation-modulatory activities, was historically thought to be the only type of fat present in adult humans. The recent demonstration of functional brown adipose tissue in adults, which is highly metabolic, shifted this paradigm. Additionally, recent studies demonstrate the ability of white adipose tissue to be induced toward the brown adipose phenotype - "beige" or "brite" adipose tissue - in a process referred to as "browning." While these adipose tissue depots are under investigation in the context of obesity, new evidence suggests a maladaptive role in other metabolic disturbances including cancer-associated cachexia, which is the topic of this review. This syndrome is multifactorial in nature and is an independent factor associated with poor prognosis. Here, we review the contributions of all three adipose depots - white, brown, and beige - to the development and progression of cancer-associated cachexia. Specifically, we focus on the local and systemic processes involving these adipose tissues that lead to increased energy expenditure and sustained negative energy balance. We highlight key findings from both animal and human studies and discuss areas within the field that need further exploration. Impact statement Cancer-associated cachexia (CAC) is a complex, multifactorial syndrome that negatively impacts patient quality of live and prognosis. This work reviews a component of CAC that lacks prior discussion: adipose tissue contributions. Uniquely, it discusses all three types of adipose tissue, white, beige, and brown, their interactions, and their contributions to the development and progression of CAC. Summarizing key bench and clinical studies, it provides information that will be useful to both basic and clinical researchers in designing

  11. The Effect of Resveratrol and Quercetin Treatment on PPAR Mediated Uncoupling Protein (UCP- 1, 2, and 3 Expression in Visceral White Adipose Tissue from Metabolic Syndrome Rats

    Directory of Open Access Journals (Sweden)

    Vicente Castrejón-Tellez

    2016-07-01

    Full Text Available Uncoupling proteins (UCPs are members of the mitochondrial anion carrier superfamily involved in the control of body temperature and energy balance regulation. They are currently proposed as therapeutic targets for treating obesity and metabolic syndrome (MetS. We studied the gene expression regulation of UCP1, -2, and -3 in abdominal white adipose tissue (WAT from control and MetS rats treated with two doses of a commercial mixture of resveratrol (RSV and quercetin (QRC. We found that UCP2 was the predominantly expressed isoform, UCP3 was present at very low levels, and UCP1 was undetectable. The treatment with RSV + QRC did not modify UCP3 levels; however, it significantly increased UCP2 mRNA in control and MetS rats in association with an increase in oleic and linoleic fatty acids. WAT from MetS rats showed a significantly increased expression of peroxisome proliferator-activated receptor (PPAR-α and PPAR-γ when compared to the control group. Furthermore, PPAR-α protein levels were increased by the highest dose of RSV + QRC in the control and MetS groups. PPAR-γ expression was only increased in the control group. We conclude that the RSV + QRC treatment leads to overexpression of UCP2, which is associated with an increase in MUFA and PUFA, which might increase PPAR-α expression.

  12. Automatic Segmentation of Abdominal Adipose Tissue in MRI

    DEFF Research Database (Denmark)

    Mosbech, Thomas Hammershaimb; Pilgaard, Kasper; Vaag, Allan

    2011-01-01

    This paper presents a method for automatically segmenting abdominal adipose tissue from 3-dimensional magnetic resonance images. We distinguish between three types of adipose tissue; visceral, deep subcutaneous and superficial subcutaneous. Images are pre-processed to remove the bias field effect...... of intensity in-homogeneities. This effect is estimated by a thin plate spline extended to fit two classes of automatically sampled intensity points in 3D. Adipose tissue pixels are labelled with fuzzy c-means clustering and locally determined thresholds. The visceral and subcutaneous adipose tissue...... are separated using deformable models, incorporating information from the clustering. The subcutaneous adipose tissue is subdivided into a deep and superficial part by means of dynamic programming applied to a spatial transformation of the image data. Regression analysis shows good correspondences between our...

  13. Inflammatory peptides derived from adipose tissue

    Directory of Open Access Journals (Sweden)

    Barzilai Nir

    2005-01-01

    Full Text Available Abstract The low-grade inflammation seen with aging is noted particularly in subjects with the metabolic syndrome of aging. Insulin resistance, obesity/abdominal obesity, and risks for many age-related diseases characterize this common syndrome. It is becoming clear that this increased adipose tissue is not simply a reservoir for excess nutrients, but rather an active and dynamic organ capable of expressing several cytokines and other fat-derived peptides (FDP. Some, but not all, FDP may have a role in development of the metabolic syndrome but there is no evidence that these FDP are causing inflammation directly. We suggest that high levels of inflammatory peptides are markers for obesity/abdominal obesity seen with aging, but some may not necessarily have a causative role in the development of inflammation.

  14. The Ontogeny of Brown Adipose Tissue.

    Science.gov (United States)

    Symonds, Michael E; Pope, Mark; Budge, Helen

    2015-01-01

    There are three different types of adipose tissue (AT)-brown, white, and beige-that differ with stage of development, species, and anatomical location. Of these, brown AT (BAT) is the least abundant but has the greatest potential impact on energy balance. BAT is capable of rapidly producing large amounts of heat through activation of the unique uncoupling protein 1 (UCP1) located within the inner mitochondrial membrane. White AT is an endocrine organ and site of lipid storage, whereas beige AT is primarily white but contains some cells that possess UCP1. BAT first appears in the fetus around mid-gestation and is then gradually lost through childhood, adolescence, and adulthood. We focus on the interrelationships between adipocyte classification, anatomical location, and impact of diet in early life together with the extent to which fat development differs between the major species examined. Ultimately, novel dietary interventions designed to reactivate BAT could be possible.

  15. FEEDING INFLUENCES ADIPOSE TISSUE RESPONSES TO EXERCISE IN OVERWEIGHT MEN.

    Science.gov (United States)

    Chen, Yung-Chih; Travers, Rebecca L; Walhin, Jean-Philippe; Gonzalez, Javier T; Koumanov, Francoise; Betts, James A; Thompson, Dylan

    2017-03-14

    Feeding profoundly affects metabolic responses to exercise in various tissues but the effect of feeding status on human adipose tissue responses to exercise has never been studied. Ten healthy overweight men aged 26 ± 5 years (mean ± SD) with a waist circumference of 105 ± 10 cm walked at 60% of maximum oxygen uptake under either FASTED or FED conditions in a randomised, counterbalanced design. Feeding comprised 648 ± 115 kcal 2 h before exercise. Blood samples were collected at regular intervals to examine changes in metabolic parameters and adipokine concentrations. Adipose tissue samples were obtained at baseline and one hour post-exercise to examine changes in adipose tissue mRNA expression and secretion of selected adipokines ex-vivo. Adipose tissue mRNA expression of PDK4, ATGL, HSL, FAT/CD36, GLUT4 and IRS2 in response to exercise were lower in FED compared to FASTED conditions (all p ≤ 0.05). Post-exercise adipose IRS2 protein was affected by feeding (p ≤ 0.05), but Akt2, AMPK, IRS1, GLUT4, PDK4 and HSL protein levels were not different. Feeding status did not impact serum and ex-vivo adipose secretion of IL-6, leptin or adiponectin in response to exercise. This is the first study to show that feeding prior to acute exercise affects post-exercise adipose tissue gene expression and we propose that feeding is likely to blunt long-term adipose tissue adaptation to regular exercise.

  16. Porous decellularized adipose tissue foams for soft tissue regeneration.

    Science.gov (United States)

    Yu, Claire; Bianco, Juares; Brown, Cody; Fuetterer, Lydia; Watkins, John F; Samani, Abbas; Flynn, Lauren E

    2013-04-01

    To design tissue-specific bioscaffolds with well-defined properties and 3-D architecture, methods were developed for preparing porous foams from enzyme-solubilized human decellularized adipose tissue (DAT). Additionally, a technique was established for fabricating "bead foams" comprised of interconnected networks of porous DAT beads fused through a controlled freeze-thawing and lyophilization procedure. In characterization studies, the foams were stable without the need for chemical crosslinking, with properties that could be tuned by controlling the protein concentration and freezing rate during synthesis. Adipogenic differentiation studies with human adipose-derived stem cells (ASCs) suggested that stiffness influenced ASC adipogenesis on the foams. In support of our previous work with DAT scaffolds and microcarriers, the DAT foams and bead foams strongly supported adipogenesis and were also adipo-inductive, as demonstrated by glycerol-3-phosphate dehydrogenase (GPDH) enzyme activity, endpoint RT-PCR analysis of adipogenic gene expression, and intracellular lipid accumulation. Adipogenic differentiation was enhanced on the microporous DAT foams, potentially due to increased cell-cell interactions in this group. In vivo assessment in a subcutaneous Wistar rat model demonstrated that the DAT bioscaffolds were well tolerated and integrated into the host tissues, supporting angiogenesis and adipogenesis. The DAT-based foams induced a strong angiogenic response, promoted inflammatory cell migration and gradually resorbed over the course of 12 weeks, demonstrating potential as scaffolds for wound healing and soft tissue regeneration.

  17. Resistin induces lipolysis and suppresses adiponectin secretion in cultured human visceral adipose tissue.

    Science.gov (United States)

    Chen, Neng; Zhou, Lingmei; Zhang, Zixiang; Xu, Jiaying; Wan, Zhongxiao; Qin, Liqiang

    2014-11-01

    Resistin is an adipokine secreted from adipose tissue, which is likely involved in the development of obesity and insulin resistance via its interaction with other organs, as well as affecting adipose tissue function. The impact of resistin treatment on lipolysis and adiponectin secretion in human visceral adipose tissue is currently unknown. Mesenteric adipose tissue samples were obtained from 14 male subjects [age 54±6 yr, body mass index (BMI) 23.59±0.44 kg/m(2)] undergoing abdominal surgeries. Adipose tissues were cultured and treated with resistin (100 ng/mL, 24h) in the absence or presence of different signaling inhibitors: H89 (1 μM), PD98059 (25 μM) and SB201290 (20 μM) for glycerol and non-esterified fatty acid (NEFA) measurement. Adiponectin level from media at 24 h was also measured via ELISA. Adipose tissue minces after resistin incubation (100 ng/mL, 24 h) were also collected for further Western blotting analysis. Resistin resulted in significant induction of glycerol (3.62±0.57 vs. 5.30±1.11 mmol/L/g tissue, ptissue, ptissue, ptissues via its effect on adipose tissue function.

  18. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue

    Directory of Open Access Journals (Sweden)

    Miroslav Šram

    2015-01-01

    Full Text Available Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT and visceral adipose tissue (VAT, the latter being highly associated with coronary artery disease (CAD. Expansion of epicardial adipose tissue (EAT is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1 the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2 determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value.

  19. Epicardial Adipose Tissue Is Nonlinearly Related to Anthropometric Measures and Subcutaneous Adipose Tissue.

    Science.gov (United States)

    Šram, Miroslav; Vrselja, Zvonimir; Lekšan, Igor; Ćurić, Goran; Selthofer-Relatić, Kristina; Radić, Radivoje

    2015-01-01

    Introduction. Adipose tissue is the largest endocrine organ, composed of subcutaneous (SAT) and visceral adipose tissue (VAT), the latter being highly associated with coronary artery disease (CAD). Expansion of epicardial adipose tissue (EAT) is linked to CAD. One way of assessing the CAD risk is with low-cost anthropometric measures, although they are inaccurate and cannot discriminate between VAT and SAT. The aim of this study is to evaluate (1) the relationship between EAT thickness, SAT thickness and anthropometric measures in a cohort of patients assessed at the cardiology unit and (2) determine predictive power of anthropometric measures and EAT and SAT thickness in establishment of CAD. Methods. Anthropometric measures were obtained from 53 CAD and 42 non-CAD patients. Vascular and structural statuses were obtained with coronarography and echocardiography, as well as measurements of the EAT and SAT thickness. Results. Anthropometric measures showed moderate positive correlation with EAT and SAT thickness. Anthropometric measures and SAT follow nonlinear S curve relationship with EAT. Strong nonlinear power curve relationship was observed between EAT and SAT thinner than 10 mm. Anthropometric measures and EAT and SAT were poor predictors of CAD. Conclusion. Anthropometric measures and SAT have nonlinear relationship with EAT. EAT thickness and anthropometric measures have similar CAD predictive value.

  20. Hepatic oleate regulates adipose tissue lipogenesis and fatty acid oxidation.

    Science.gov (United States)

    Burhans, Maggie S; Flowers, Matthew T; Harrington, Kristin R; Bond, Laura M; Guo, Chang-An; Anderson, Rozalyn M; Ntambi, James M

    2015-02-01

    Hepatic steatosis is associated with detrimental metabolic phenotypes including enhanced risk for diabetes. Stearoyl-CoA desaturases (SCDs) catalyze the synthesis of MUFAs. In mice, genetic ablation of SCDs reduces hepatic de novo lipogenesis (DNL) and protects against diet-induced hepatic steatosis and adiposity. To understand the mechanism by which hepatic MUFA production influences adipose tissue stores, we created two liver-specific transgenic mouse models in the SCD1 knockout that express either human SCD5 or mouse SCD3, that synthesize oleate and palmitoleate, respectively. We demonstrate that hepatic de novo synthesized oleate, but not palmitoleate, stimulate hepatic lipid accumulation and adiposity, reversing the protective effect of the global SCD1 knockout under lipogenic conditions. Unexpectedly, the accumulation of hepatic lipid occurred without induction of the hepatic DNL program. Changes in hepatic lipid composition were reflected in plasma and in adipose tissue. Importantly, endogenously synthesized hepatic oleate was associated with suppressed DNL and fatty acid oxidation in white adipose tissue. Regression analysis revealed a strong correlation between adipose tissue lipid fuel utilization and hepatic and adipose tissue lipid storage. These data suggest an extrahepatic mechanism where endogenous hepatic oleate regulates lipid homeostasis in adipose tissues.

  1. Role of adipose tissue in the pathogenesis of cardiac arrhythmias.

    Science.gov (United States)

    Samanta, Rahul; Pouliopoulos, Jim; Thiagalingam, Aravinda; Kovoor, Pramesh

    2016-01-01

    Epicardial adipose tissue is present in normal healthy individuals. It is a unique fat depot that, under physiologic conditions, plays a cardioprotective role. However, excess epicardial adipose tissue has been shown to be associated with prevalence and severity of atrial fibrillation. In arrhythmogenic right ventricular cardiomyopathy and myotonic dystrophy, fibrofatty infiltration of the myocardium is associated with ventricular arrhythmias. In the ovine model of ischemic cardiomyopathy, the presence of intramyocardial adipose or lipomatous metaplasia has been associated with increased propensity to ventricular tachycardia. These observations suggest a role of adipose tissue in the pathogenesis of cardiac arrhythmias. In this article, we review the role of cardiac adipose tissue in various cardiac arrhythmias and discuss the possible pathophysiologic mechanisms.

  2. 0Adipose-derived stem cells: Implications in tissue regeneration

    Institute of Scientific and Technical Information of China (English)

    Wakako; Tsuji; J; Peter; Rubin; Kacey; G; Marra

    2014-01-01

    Adipose-derived stem cells(ASCs) are mesenchymal stem cells(MSCs) that are obtained from abundant adipose tissue, adherent on plastic culture flasks, can be expanded in vitro, and have the capacity to differ-entiate into multiple cell lineages. Unlike bone marrow-derived MSCs, ASCs can be obtained from abundant adipose tissue by a minimally invasive procedure, which results in a high number of cells. Therefore, ASCs are promising for regenerating tissues and organs dam-aged by injury and diseases. This article reviews the implications of ASCs in tissue regeneration.

  3. M1-M2 balancing act in white adipose tissue browning – a new role for RIP140

    OpenAIRE

    Liu, Pu-Ste; LIN, YI-WEI; Burton, Frank H; Wei, Li-Na

    2015-01-01

    A “Holy Grail” sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophage...

  4. The Effect of Resveratrol and Quercetin Treatment on PPAR Mediated Uncoupling Protein (UCP-) 1, 2, and 3 Expression in Visceral White Adipose Tissue from Metabolic Syndrome Rats

    OpenAIRE

    2016-01-01

    Uncoupling proteins (UCPs) are members of the mitochondrial anion carrier superfamily involved in the control of body temperature and energy balance regulation. They are currently proposed as therapeutic targets for treating obesity and metabolic syndrome (MetS). We studied the gene expression regulation of UCP1, -2, and -3 in abdominal white adipose tissue (WAT) from control and MetS rats treated with two doses of a commercial mixture of resveratrol (RSV) and quercetin (QRC). We found that U...

  5. Treatment with TUG891, a free fatty acid receptor 4 agonist, restores adipose tissue metabolic dysfunction following chronic sleep fragmentation in mice

    DEFF Research Database (Denmark)

    Gozal, D; Qiao, Z; Almendros, I

    2016-01-01

    BACKGROUND: Sleep fragmentation (SF), a frequent occurrence in multiple sleep and other diseases leads to increased food intake and insulin resistance via increased macrophage activation and inflammation in visceral white adipose tissue (VWAT). Free fatty acid receptor 4 (FFA4) is reduced in pedi...... FFA4 activity may serve as potentially useful adjunctive therapies for sleep disorders accompanied by metabolic morbidity.International Journal of Obesity accepted article preview online, 16 March 2016. doi:10.1038/ijo.2016.37....

  6. Brown adipose tissue and novel therapeutic approaches to treat metabolic disorders.

    Science.gov (United States)

    Roman, Sabiniano; Agil, Ahmad; Peran, Macarena; Alvaro-Galue, Eduardo; Ruiz-Ojeda, Francisco J; Fernández-Vázquez, Gumersindo; Marchal, Juan A

    2015-04-01

    In humans, 2 functionally different types of adipose tissue coexist: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT is involved in energy storage, whereas BAT is involved in energy expenditure. Increased amounts of WAT may contribute to the development of metabolic disorders, such as obesity-associated type 2 diabetes mellitus and cardiovascular diseases. In contrast, the thermogenic function of BAT allows high consumption of fatty acids because of the activity of uncoupling protein 1 in the internal mitochondrial membrane. Interestingly, obesity reduction and insulin sensitization have been achieved by BAT activation-regeneration in animal models. This review describes the origin, function, and differentiation mechanisms of BAT to identify new therapeutic strategies for the treatment of metabolic disorders related to obesity. On the basis of the animal studies, novel approaches for BAT regeneration combining stem cells from the adipose tissue with active components, such as melatonin, may have potential for the treatment of metabolic disorders in humans.

  7. The mechanism of functional vasodilatation in rabbit epigastric adipose tissue.

    Science.gov (United States)

    Lewis, G P; Mattews, J

    1970-03-01

    1. The effect of close-arterial infusions of fat-mobilizing substances has been examined on the release of free fatty acids and blood flow in the epigastric adipose tissue of rabbits.2. All the fat mobilizers in addition to causing the release of free fatty acids also caused an increased blood flow in the fat tissue.3. Both the fat mobilization and the vasodilatation continued for an hour or so after the end of infusion.4. Although no vasodilator substance could be detected in the venous effluent from the activated adipose tissue, a vasodilator could be detected in acid-ether extracts of adipose tissue excised during a period of fat mobilization.5. It is suggested that a vasodilator substance is released or formed in adipose tissue during fat mobilization and that this substance accounts for the vasodilatation accompanying activity in the tissue.

  8. Does Adipose Tissue Thermogenesis Play a Role in Metabolic Health?

    Directory of Open Access Journals (Sweden)

    Craig Porter

    2013-01-01

    Full Text Available The function ascribed to brown adipose tissue in humans has long been confined to thermoregulation in neonates, where this thermogenic capacity was thought lost with maturation. Recently, brown adipose tissue depots have been identified in adult humans. The significant oxidative capacity of brown adipocytes and the ability of their mitochondria to respire independently of ATP production, has led to renewed interest in the role that these adipocytes play in human energy metabolism. In our view, there is a need for robust physiological studies determining the relationship between molecular signatures of brown adipose tissue, adipose tissue mitochondrial function, and whole body energy metabolism, in order to elucidate the significance of thermogenic adipose tissue in humans. Until such information is available, the role of thermogenic adipose tissue in human metabolism and the potential that these adipocytes may prevent or treat obesity and metabolic diseases in humans will remain unknown. In this article, we summarize the recent literature pertaining to brown adipose tissue function with the aims of drawing the readers’ attention to the lack of data concerning the role of brown adipocytes in human physiology, and to the potential limitations of current research strategies.

  9. Adipose tissue macrophages: the inflammatory link between obesity and cancer?

    Science.gov (United States)

    Wagner, Marek; Samdal Steinskog, Eli Sihn; Wiig, Helge

    2015-04-01

    Obesity has increased dramatically over the last three decades. Thus, epidemiological evidence linking obesity and cancer has ignited our interest in the relationship between adipose tissue mass and cancer development. Obesity is defined as an excess of adipose tissue that is typified by a chronic, low-grade inflammatory response instigated by macrophage infiltration. Therefore, in this review, we will discuss the putative causal relationship between obesity-induced chronic inflammation and cancer with particular focus on adipose tissue macrophages. Chronic, low-grade inflammation has long been associated with cancer initiation, promotion and progression. Therefore, signals derived from adipose tissue macrophages may play a significant role in carcinogenesis. In this review we will discuss the molecular mechanisms of cancer development in obesity and highlight possible therapeutic strategies aiming at adipose tissue macrophages. The strong correlation between tumor-associated macrophage infiltration and tumor growth and progression emphasizes the value of macrophages as an effective therapeutic target. It remains to be deciphered to what extent adipose tissue macrophages contribute to these processes, especially in tumors growing within or adjacent to adipose tissue. More effort should also be placed on elucidating macrophage differences between humans and mice that may lead to the development of more effective diagnostic and therapeutic strategies.

  10. Adipose tissue and skeletal muscle blood flow during mental stress

    Energy Technology Data Exchange (ETDEWEB)

    Linde, B.; Hjemdahl, P.; Freyschuss, U.; Juhlin-Dannfelt, A.

    1989-01-01

    Mental stress (a modified Stroop color word conflict test (CWT)) increased adipose tissue blood flow (ATBF; 133Xe clearance) by 70% and reduced adipose tissue vascular resistance (ATR) by 25% in healthy male volunteers. The vasculatures of adipose tissue (abdomen as well as thigh), skeletal muscle of the calf (133Xe clearance), and the entire calf (venous occlusion plethysmography) responded similarly. Arterial epinephrine (Epi) and glycerol levels were approximately doubled by stress. Beta-Blockade by metoprolol (beta 1-selective) or propranolol (nonselective) attenuated CWT-induced tachycardia similarly. Metoprolol attenuated stress-induced vasodilation in the calf and tended to do so in adipose tissue. Propranolol abolished vasodilation in the calf and resulted in vasoconstriction during CWT in adipose tissue. Decreases in ATR, but not in skeletal muscle or calf vascular resistances, were correlated to increases in arterial plasma glycerol (r = -0.42, P less than 0.05), whereas decreases in skeletal muscle and calf vascular resistances, but not in ATR, were correlated to increases in arterial Epi levels (r = -0.69, P less than 0.01; and r = -0.43, P less than 0.05, respectively). The results suggest that mental stress increases nutritive blood flow in adipose tissue and skeletal muscle considerably, both through the elevation of perfusion pressure and via vasodilatation. Withdrawal of vasoconstrictor nerve activity, vascular beta 2-adrenoceptor stimulation by circulating Epi, and metabolic mechanisms (in adipose tissue) may contribute to the vasodilatation.

  11. Role of inflammatory factors and adipose tissue in pathogenesis of rheumatoid arthritis and osteoarthritis. Part I: Rheumatoid adipose tissue.

    Science.gov (United States)

    Sudoł-Szopińska, Iwona; Kontny, Ewa; Zaniewicz-Kaniewska, Katarzyna; Prohorec-Sobieszek, Monika; Saied, Fadhil; Maśliński, Włodzimierz

    2013-06-01

    For many years, it was thought that synovial cells and chondrocytes are the only sources of proinflammatory cytokines and growth factors found in the synovial fluid in patients suffering from osteoarthritis and rheumatoid arthritis. Currently, it is more and more frequently indicated that adipose tissue plays a significant role in the pathogenesis of these diseases as well as that a range of pathological processes that take place in the adipose tissue, synovial membrane and cartilage are interconnected. The adipose tissue is considered a specialized form of the connective tissue containing various types of cells which produce numerous biologically active factors. The latest studies reveal that, similarly to the synovial membrane, articular adipose tissue may take part in the local inflammatory response and affect the metabolism of the cartilage and subchondral osseous tissue. In in vitro conditions, the explants of this tissue obtained from patients suffering from osteoarthritis and rheumatoid arthritis produce similar pro- and anti-inflammatory cytokines to the explants of the synovial membrane. At this stage already, knowledge translates into imaging diagnostics. In radiological images, the shadowing of the periarticular soft tissues may not only reflect synovial membrane pathologies or joint effusion, but may also suggest inflammatory edema of the adipose tissue. On ultrasound examinations, abnormal presentation of the adipose tissue, i.e. increased echogenicity and hyperemia, may indicate its inflammation. Such images have frequently been obtained during ultrasound scanning and have been interpreted as inflammation, edema, hypertrophy or fibrosis of the adipose tissue. At present, when the knowledge concerning pathogenic mechanisms is taken into account, abnormal echogenicity and hyperemia of the adipose tissue may be considered as a proof of its inflammation. In the authors' own practice, the inflammation of the adipose tissue usually accompanies synovitis

  12. Adipose tissue content and distribution in children and adolescents with bronchial asthma.

    Science.gov (United States)

    Umławska, Wioleta

    2015-02-01

    The excess of adipose tissue and the pattern of adipose tissue distribution in the body seem to play an important role in the complicated dependencies between obesity and risk of developing asthma. The aim of the present study was to determine nutritional status in children and adolescents with bronchial asthma with special emphasis on adipose tissue distribution evaluated on the basis of skin-fold thicknesses, and to determine the relationships between patterns of adipose tissue distribution and the course of the disease. Anthropometric data on height, weight, circumferences and skin-fold thicknesses were extracted from the medical histories of 261 children diagnosed with asthma bronchitis. Values for children with asthma were compared to Polish national growth reference charts. Distribution of subcutaneous adipose tissue was evaluated using principal components analysis (PCA). Multivariate linear regression analyses tested the effect of three factors on subcutaneous adipose tissue distribution: type of asthma, the severity of the disease and the duration of the disease. Mean body height in the children examined in this study was lower than in their healthy peers. Mean BMI and skin-fold thicknesses were significantly higher and lean body mass was lower in the study group. Excess body fat was noted, especially in girls. Adipose tissue was preferentially deposited in the trunk in girls with severe asthma, as well as in those who had been suffering from asthma for a longer time. The type of asthma, atopic or non-atopic, had no observable effect on subcutaneous adipose tissue distribution in children examined. The data suggest that long-treated subjects and those with severe bronchial asthma accumulate more adipose tissue on the trunk. It is important to regularly monitor nutritional status in children with asthma, especially in those receiving high doses of systemic or inhaled glucocorticosteroids, and long-term treatment as well. Copyright © 2014 Elsevier Ltd. All

  13. Injury-Induced Insulin Resistance in Adipose Tissue

    OpenAIRE

    Williams, Vanessa L.; Martin, Rachel E.; Franklin, John L.; Hardy, Robert. W.; Messina, Joseph L.

    2012-01-01

    Hyperglycemia and insulin resistance are common findings in critical illness. Patients in the surgical ICU are frequently treated for this ‘critical illness diabetes’ with intensive insulin therapy, resulting in a substantial reduction in morbidity and mortality. Adipose tissue is an important insulin target tissue, but it is not known whether adipose tissue is affected by critical illness diabetes. In the present study, a rodent model of critical illness diabetes was used to determine whethe...

  14. Brown Adipose Tissue Bioenergetics: A New Methodological Approach

    Science.gov (United States)

    Calderon‐Dominguez, María; Alcalá, Martín; Sebastián, David; Zorzano, Antonio; Viana, Marta; Serra, Dolors

    2017-01-01

    The rediscovery of brown adipose tissue (BAT) in humans and its capacity to oxidize fat and dissipate energy as heat has put the spotlight on its potential as a therapeutic target in the treatment of several metabolic conditions including obesity and diabetes. To date the measurement of bioenergetics parameters has required the use of cultured cells or extracted mitochondria with the corresponding loss of information in the tissue context. Herein, we present a method to quantify mitochondrial bioenergetics directly in BAT. Based on XF Seahorse Technology, we assessed the appropriate weight of the explants, the exact concentration of each inhibitor in the reaction, and the specific incubation time to optimize bioenergetics measurements. Our results show that BAT basal oxygen consumption is mostly due to proton leak. In addition, BAT presents higher basal oxygen consumption than white adipose tissue and a positive response to b‐adrenergic stimulation. Considering the whole tissue and not just subcellular populations is a direct approach that provides a realistic view of physiological respiration. In addition, it can be adapted to analyze the effect of potential activators of thermogenesis, or to assess the use of fatty acids or glucose as a source of energy. PMID:28435771

  15. Macrophage Migration Inhibitory Factor in Acute Adipose Tissue Inflammation.

    Directory of Open Access Journals (Sweden)

    Bong-Sung Kim

    Full Text Available Macrophage migration inhibitory factor (MIF is a pleiotropic cytokine and has been implicated in inflammatory diseases. However, little is known about the regulation of MIF in adipose tissue and its impact on wound healing. The aim of this study was to investigate MIF expression in inflamed adipose and determine its role in inflammatory cell recruitment and wound healing. Adipose tissue was harvested from subcutaneous adipose tissue layers of 24 healthy subjects and from adipose tissue adjacent to acutely inflamed wounds of 21 patients undergoing wound debridement. MIF protein and mRNA expression were measured by ELISA and RT-PCR. Cell-specific MIF expression was visualized by immunohistochemistry. The functional role of MIF in cell recruitment was investigated by a chemotaxis assay and by flow cytometry of labeled macrophages that were injected into Mif-/-and wildtype mice. Wound healing was evaluated by an in vitro scratch assay on human fibroblast monolayers. MIF protein levels of native adipose tissue and supernatants from acutely inflamed wounds were significantly elevated when compared to healthy controls. MIF mRNA expression was increased in acutely inflamed adipose tissue indicating the activation of MIF gene transcription in response to adipose tissue inflammation. MIF is expressed in mature adipocytes and in infiltrated macrophages. Peripheral blood mononuclear cell migration was significantly increased towards supernatants derived from inflamed adipose tissue. This effect was partially abrogated by MIF-neutralizing antibodies. Moreover, when compared to wildtype mice, Mif-/-mice showed reduced infiltration of labeled macrophages into LPS-stimulated epididymal fat pads in vivo. Finally, MIF antibodies partially neutralized the detrimental effect of MIF on fibroblast wound healing. Our results indicate that increased MIF expression and rapid activation of the MIF gene in fat tissue adjacent to acute wound healing disorders may play a

  16. Sex matters: The effects of biological sex on adipose tissue biology and energy metabolism

    Directory of Open Access Journals (Sweden)

    Teresa G. Valencak

    2017-08-01

    Full Text Available Adipose tissue is a complex and multi-faceted organ. It responds dynamically to internal and external stimuli, depending on the developmental stage and activity of the organism. The most common functional subunits of adipose tissue, white and brown adipocytes, regulate and respond to endocrine processes, which then determine metabolic rate as well as adipose tissue functions. While the molecular aspects of white and brown adipose biology have become clearer in the recent past, much less is known about sex-specific differences in regulation and deposition of adipose tissue, and the specific role of the so-called pink adipocytes during lactation in females. This review summarises the current understanding of adipose tissue dynamics with a focus on sex-specific differences in adipose tissue energy metabolism and endocrine functions, focussing on mammalian model organisms as well as human-derived data. In females, pink adipocytes trans-differentiate during pregnancy from subcutaneous white adipocytes and are responsible for milk-secretion in mammary glands. Overlooking biological sex variation may ultimately hamper clinical treatments of many aspects of metabolic disorders.

  17. Hypoxia and adipose tissue function and dysfunction in obesity.

    Science.gov (United States)

    Trayhurn, Paul

    2013-01-01

    The rise in the incidence of obesity has led to a major interest in the biology of white adipose tissue. The tissue is a major endocrine and signaling organ, with adipocytes, the characteristic cell type, secreting a multiplicity of protein factors, the adipokines. Increases in the secretion of a number of adipokines occur in obesity, underpinning inflammation in white adipose tissue and the development of obesity-associated diseases. There is substantial evidence, particularly from animal studies, that hypoxia develops in adipose tissue as the tissue mass expands, and the reduction in Po(2) is considered to underlie the inflammatory response. Exposure of white adipocytes to hypoxic conditions in culture induces changes in the expression of >1,000 genes. The secretion of a number of inflammation-related adipokines is upregulated by hypoxia, and there is a switch from oxidative metabolism to anaerobic glycolysis. Glucose utilization is increased in hypoxic adipocytes with corresponding increases in lactate production. Importantly, hypoxia induces insulin resistance in fat cells and leads to the development of adipose tissue fibrosis. Many of the responses of adipocytes to hypoxia are initiated at Po(2) levels above the normal physiological range for adipose tissue. The other cell types within the tissue also respond to hypoxia, with the differentiation of preadipocytes to adipocytes being inhibited and preadipocytes being transformed into leptin-secreting cells. Overall, hypoxia has pervasive effects on the function of adipocytes and appears to be a key factor in adipose tissue dysfunction in obesity.

  18. TAF7L modulates brown adipose tissue formation

    OpenAIRE

    ZHOU, HAIYING; Wan, Bo; Grubisic, Ivan; Kaplan, Tommy; Tjian, Robert

    2014-01-01

    eLife digest Mammals produce two distinct types of adipose tissue: white adipose tissue (white fat) is the more common type and is used to store energy; brown adipose tissue (brown fat) is mostly found in young animals and infants, and it plays an important role in dissipating energy as heat rather than storing it in fat for future use. In adults, higher levels of brown fat are associated with lower levels of fat overall, so there is considerable interest in learning more about this form of f...

  19. Self-synthesized extracellular matrix contributes to mature adipose tissue regeneration in a tissue engineering chamber.

    Science.gov (United States)

    Zhan, Weiqing; Chang, Qiang; Xiao, Xiaolian; Dong, Ziqing; Zeng, Zhaowei; Gao, Jianhua; Lu, Feng

    2015-01-01

    The development of an engineered adipose tissue substitute capable of supporting reliable, predictable, and complete fat tissue regeneration would be of value in plastic and reconstructive surgery. For adipogenesis, a tissue engineering chamber provides an optimized microenvironment that is both efficacious and reproducible; however, for reasons that remain unclear, tissues regenerated in a tissue engineering chamber consist mostly of connective rather than adipose tissue. Here, we describe a chamber-based system for improving the yield of mature adipose tissue and discuss the potential mechanism of adipogenesis in tissue-chamber models. Adipose tissue flaps with independent vascular pedicles placed in chambers were implanted into rabbits. Adipose volume increased significantly during the observation period (week 1, 2, 3, 4, 16). Histomorphometry revealed mature adipose tissue with signs of adipose tissue remolding. The induced engineered constructs showed high-level expression of adipogenic (peroxisome proliferator-activated receptor γ), chemotactic (stromal cell-derived factor 1a), and inflammatory (interleukin 1 and 6) genes. In our system, the extracellular matrix may have served as a scaffold for cell migration and proliferation, allowing mature adipose tissue to be obtained in a chamber microenvironment without the need for an exogenous scaffold. Our results provide new insights into key elements involved in the early development of adipose tissue regeneration.

  20. Adipose Tissue: Sanctuary for HIV/SIV Persistence and Replication.

    Science.gov (United States)

    Pallikkuth, Suresh; Mohan, Mahesh

    2015-12-01

    This commentary highlights new findings from a recent study identifying adipose tissue as a potential HIV reservoir and a major site of inflammation during chronic human/simian immunodeficiency virus (HIV/SIV) infection. A concise discussion about upcoming challenges and new research avenues for reducing chronic adipose inflammation during HIV/SIV infection is presented.

  1. Interleukin-6 production in human subcutaneous abdominal adipose tissue

    DEFF Research Database (Denmark)

    Lyngsø, Dorthe; Simonsen, Lene; Bülow, Jens

    2002-01-01

    The interleukin-6 (IL-6) output from subcutaneous, abdominal adipose tissue was studied in nine healthy subjects before, during and for 3 h after 1 h two-legged bicycle exercise at 60 % maximal oxygen consumption. Seven subjects were studied in control experiments without exercise. The adipose ti...

  2. Altered white adipose tissue protein profile in C57BL/6J mice displaying delipidative, inflammatory, and browning characteristics after bitter melon seed oil treatment.

    Directory of Open Access Journals (Sweden)

    Cheng-Hsien Hsieh

    Full Text Available OBJECTIVE: We have previously shown that bitter melon seed oil (BMSO, which is rich in cis-9, trans-11, trans-13 conjugated linolenic acid, is more potent than soybean oil in attenuating body fat deposition in high-fat diet-induced obese C57BL/6J mice. The aim of this study was to obtain a comprehensive insight into how white adipose tissue (WAT is affected by BMSO administration and to explore the underlying mechanisms of the anti-adiposity effect of BMSO. METHODS AND RESULTS: A proteomic approach was used to identify proteins differentially expressed in the WAT of mice fed diets with or without BMSO for 11 wks. The WAT was also analyzed histologically for morphological changes. Two-dimensional gel electrophoresis (pH 4-7 revealed 32 spots showing a statistically significant difference (P2-fold change. Combined with histological evidence of macrophage infiltration and brown adipocyte recruitment, the proteomic and immunoblotting data showed that the WAT in mice subjected to long-term high dose BMSO administration was characterized by reduced caveolae formation, increased ROS insult, tissue remodeling/repair, mitochondria uncoupling, and stabilization of the actin cytoskeleton, this last change being putatively related to an increased inflammatory response. CONCLUSION: The anti-adiposity effect of BMSO is associated with WAT delipidation, inflammation, and browning. Some novel proteins participating in these processes were identified. In addition, the BMSO-mediated WAT browning may account for the increased inflammation without causing adverse metabolic effects.

  3. Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity.

    Science.gov (United States)

    Okada, Sadanori; Kozuka, Chisayo; Masuzaki, Hiroaki; Yasue, Shintaro; Ishii-Yonemoto, Takako; Tanaka, Tomohiro; Yamamoto, Yuji; Noguchi, Michio; Kusakabe, Toru; Tomita, Tsutomu; Fujikura, Junji; Ebihara, Ken; Hosoda, Kiminori; Sakaue, Hiroshi; Kobori, Hiroyuki; Ham, Mira; Lee, Yun Sok; Kim, Jae Bum; Saito, Yoshihiko; Nakao, Kazuwa

    2010-09-01

    Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of AGT in obese adipose tissue. In this context, we here demonstrated that the AGT messenger RNA (mRNA) level in human subcutaneous adipose tissue was significantly reduced in obese subjects as compared with nonobese subjects. Adipose tissue AGT mRNA level in obese mice was also lower as compared with their lean littermates; however, the hepatic AGT mRNA level remained unchanged. When 3T3-L1 adipocytes were cultured for a long period, the adipocytes became hypertrophic with a marked increase in the production of reactive oxygen species. Expression and secretion of AGT continued to decrease during the course of adipocyte hypertrophy. Treatment of the 3T3-L1 and primary adipocytes with reactive oxygen species (hydrogen peroxide) or tumor necrosis factor alpha caused a significant decrease in the expression and secretion of AGT. On the other hand, treatment with the antioxidant N-acetyl cysteine suppressed the decrease in the expression and secretion of AGT in the hypertrophied 3T3-L1 adipocytes. Finally, treatment of obese db/db mice with N-acetyl cysteine augmented the expression of AGT in the adipose tissue, but not in the liver. The present study demonstrates for the first time that oxidative stress dysregulates AGT in obese adipose tissue, providing a novel insight into the adipose tissue-specific interaction between the regulation of AGT and oxidative stress in the pathophysiology of obesity. Copyright 2010 Elsevier Inc. All rights reserved.

  4. Adipose tissue lymphocytes: types and roles.

    Science.gov (United States)

    Caspar-Bauguil, S; Cousin, B; Bour, S; Casteilla, L; Castiella, L; Penicaud, L; Carpéné, C

    2009-12-01

    Besides adipocytes, specialized in lipid handling and involved in energy balance regulation, white adipose tissue (WAT) is mainly composed of other cell types among which lymphocytes represent a non-negligible proportion. Different types of lymphocytes (B, alphabetaT, gammadeltaT, NK and NKT) have been detected in WAT of rodents or humans, and vary in their relative proportion according to the fat pad anatomical location. The lymphocytes found in intra-abdominal, visceral fat pads seem representative of innate immunity, while those present in subcutaneous fat depots are part of adaptive immunity, at least in mice. Both the number and the activity of the different lymphocyte classes, except B lymphocytes, are modified in obesity. Several of these modifications in the relative proportions of the lymphocyte classes depend on the degree of obesity, or on leptin concentration, or even fat depot anatomical location. Recent studies suggest that alterations of lymphocyte number and composition precede the macrophage increase and the enhanced inflammatory state of WAT found in obesity. Lymphocytes express receptors to adipokines while several proinflammatory chemokines are produced in WAT, rendering intricate crosstalk between fat and immune cells. However, the evidences and controversies available so far are in favour of an involvement of lymphocytes in the control of the number of other cells in WAT, either adipocytes or immune cells and of their secretory and metabolic activities. Therefore, immunotherapy deserves to be considered as a promising approach to treat the endocrino-metabolic disorders associated to excessive fat mass development.

  5. Brain-adipose tissue cross talk.

    Science.gov (United States)

    Bartness, Timothy J; Kay Song, C; Shi, Haifei; Bowers, Robert R; Foster, Michelle T

    2005-02-01

    While investigating the reversible seasonal obesity of Siberian hamsters, direct sympathetic nervous system (SNS) postganglionic innervation of white adipose tissue (WAT) has been demonstrated using anterograde and retrograde tract tracers. The primary function of this innervation is lipid mobilization. The brain SNS outflow to WAT has been defined using the pseudorabies virus (PRV), a retrograde transneuronal tract tracer. These PRV-labelled SNS outflow neurons are extensively co-localized with melanocortin-4 receptor mRNA, which, combined with functional data, suggests their involvement in lipolysis. The SNS innervation of WAT also regulates fat cell number, as noradrenaline inhibits and WAT denervation stimulates fat cell proliferation in vitro and in vivo respectively. The sensory innervation of WAT has been demonstrated by retrograde tract tracing, electrophysiological recording and labelling of the sensory-associated neuropeptide calcitonin gene-related peptide in WAT. Local injections of the sensory nerve neurotoxin capsaicin into WAT selectively destroy this innervation. Just as surgical removal of WAT pads triggers compensatory increases in lipid accretion by non-excised WAT depots, capsaicin-induced sensory denervation triggers increases in lipid accretion of non-capsaicin-injected WAT depots, suggesting that these nerves convey information about body fat levels to the brain. Finally, parasympathetic nervous system innervation of WAT has been suggested, but the recent finding of no WAT immunoreactivity for the possible parasympathetic marker vesicular acetylcholine transporter (VAChT) argues against this claim. Collectively, these data suggest several roles for efferent and afferent neural innervation of WAT in body fat regulation.

  6. New concepts in white adipose tissue physiology

    Energy Technology Data Exchange (ETDEWEB)

    Proença, A.R.G. [Universidade Estadual de Campinas, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Limeira, SP, Brasil, Laboratório de Biotecnologia, Faculdade de Ciências Aplicadas, Universidade Estadual de Campinas, Limeira, SP (Brazil); Sertié, R.A.L. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil); Oliveira, A.C. [Universidade Estadual do Ceará, Instituto Superior de Ciências Biomédicas, Fortaleza, CE, Brasil, Instituto Superior de Ciências Biomédicas, Universidade Estadual do Ceará, Fortaleza, CE (Brazil); Campaãa, A.B.; Caminhotto, R.O.; Chimin, P.; Lima, F.B. [Universidade de São Paulo, Instituto de Ciências Biomédicas, Departamento de Fisiologia e Biofísica, São Paulo, SP, Brasil, Departamento de Fisiologia e Biofísica, Instituto de Ciências Biomédicas, Universidade de São Paulo, São Paulo, SP (Brazil)

    2014-03-03

    Numerous studies address the physiology of adipose tissue (AT). The interest surrounding the physiology of AT is primarily the result of the epidemic outburst of obesity in various contemporary societies. Briefly, the two primary metabolic activities of white AT include lipogenesis and lipolysis. Throughout the last two decades, a new model of AT physiology has emerged. Although AT was considered to be primarily an abundant energy source, it is currently considered to be a prolific producer of biologically active substances, and, consequently, is now recognized as an endocrine organ. In addition to leptin, other biologically active substances secreted by AT, generally classified as cytokines, include adiponectin, interleukin-6, tumor necrosis factor-alpha, resistin, vaspin, visfatin, and many others now collectively referred to as adipokines. The secretion of such biologically active substances by AT indicates its importance as a metabolic regulator. Cell turnover of AT has also recently been investigated in terms of its biological role in adipogenesis. Consequently, the objective of this review is to provide a comprehensive critical review of the current literature concerning the metabolic (lipolysis, lipogenesis) and endocrine actions of AT.

  7. The Use of Adipose Tissue-Derived Progenitors in Bone Tissue Engineering - a Review

    Science.gov (United States)

    Bhattacharya, Indranil; Ghayor, Chafik; Weber, Franz E.

    2016-01-01

    2500 years ago, Hippocrates realized that bone can heal without scaring. The natural healing potential of bone is, however, restricted to small defects. Extended bone defects caused by trauma or during tumor resections still pose a huge problem in orthopedics and cranio-maxillofacial surgery. Bone tissue engineering strategies using stem cells, growth factors, and scaffolds could overcome the problems with the treatment of extended bone defects. In this review, we give a short overview on bone tissue engineering with emphasis on the use of adipose tissue-derived stem cells and small molecules.

  8. Isolation and Differentiation of Adipose-Derived Stem Cells from Porcine Subcutaneous Adipose Tissues.

    Science.gov (United States)

    Chen, Yu-Jen; Liu, Hui-Yu; Chang, Yun-Tsui; Cheng, Ying-Hung; Mersmann, Harry J; Kuo, Wen-Hung; Ding, Shih-Torng

    2016-03-31

    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. The dorsal white fat depot of porcine subcutaneous adipose tissues is sliced, minced and collagenase digested. These pADSC exhibit strong potential to differentiate into adipocytes. Moreover, the pADSC also possess multipotency, assessed by selective stem cell markers, to differentiate into various mesenchymal cell types including adipocytes, osteocytes, and chondrocytes. These pADSC can be used for clarification of molecular switches in regulating classical adipocyte differentiation or in direction to other mesenchymal cell types of mesodermal origin. Furthermore, extended lineages into cells of ectodermal and endodermal origin have recently been achieved. Therefore, pADSC derived in this protocol provide an abundant and assessable source of adult mesenchymal stem cells with full multipotency for studying adipose development and application to tissue engineering of regenerative medicine.

  9. The role of dietary fat in adipose tissue metabolism.

    Science.gov (United States)

    Fernández-Quintela, Alfredo; Churruca, Itziar; Portillo, Maria Puy

    2007-10-01

    Energy intake and expenditure tend on average to remain adjusted to each other in order to maintain a stable body weight, which is only likely to be sustained if the fuel mix oxidised is equivalent to the nutrient content of the diet. Whereas protein and carbohydrate degradation and oxidation are closely adjusted to their intakes, fat balance regulation is less precise and that fat is more likely to be stored than oxidised. It has been demonstrated that dietary fatty acids have an influence not only on the fatty acid composition of membrane phospholipids, thus modulating several metabolic processes that take place in the adipocyte, but also on the composition and the quantity of different fatty acids in adipose tissue. Moreover, dietary fatty acids also modulate eicosanoid presence, which have hormone-like activities in lipid metabolism regulation in adipose tissue. Until recently, the adipocyte has been considered to be no more than a passive tissue for storage of excess energy. However, there is now compelling evidence that adipocytes have a role as endocrine secretory cells. Some of the adipokines produced by adipose tissue, such as leptin and adiponectin, act on adipose tissue in an autocrine/paracrine manner to regulate adipocyte metabolism. Furthermore, dietary fatty acids may influence the expression of adipokines. The nutrients are among the most influential of the environmental factors that determine the way adipose tissue genes are expressed by functioning as regulators of gene transcription. Therefore, not only dietary fat amount but also dietary fat composition influence adipose tissue metabolism.

  10. Assessment of in situ adipose tissue inflammation by microdialysis

    DEFF Research Database (Denmark)

    Langkilde, Anne; Andersen, Ove; Henriksen, Jens H;

    2015-01-01

    Inflammation, and specifically adipose tissue (AT) inflammation, is part of the pathophysiology of obesity and HIV-associated lipodystrophy. Local AT protein assessment methods are limited, and AT inflammation studies have therefore primarily examined inflammatory gene expression. We therefore...

  11. Morphological and inflammatory changes in visceral adipose tissue during obesity.

    Science.gov (United States)

    Revelo, Xavier S; Luck, Helen; Winer, Shawn; Winer, Daniel A

    2014-03-01

    Obesity is a major health burden worldwide and is a major factor in the development of insulin resistance and metabolic complications such as type II diabetes. Chronic nutrient excess leads to visceral adipose tissue (VAT) expansion and dysfunction in an active process that involves the adipocytes, their supporting matrix, and immune cell infiltrates. These changes contribute to adipose tissue hypoxia, adipocyte cell stress, and ultimately cell death. Accumulation of lymphocytes, macrophages, and other immune cells around dying adipocytes forms the so-called "crown-like structure", a histological hallmark of VAT in obesity. Cross talk between immune cells in adipose tissue dictates the overall inflammatory response, ultimately leading to the production of pro-inflammatory mediators which directly induce insulin resistance in VAT. In this review, we summarize recent studies demonstrating the dramatic changes that occur in visceral adipose tissue during obesity leading to low-grade chronic inflammation and metabolic disease.

  12. Adipose-derived stem cells and periodontal tissue engineering.

    Science.gov (United States)

    Tobita, Morikuni; Mizuno, Hiroshi

    2013-01-01

    Innovative developments in the multidisciplinary field of tissue engineering have yielded various implementation strategies and the possibility of functional tissue regeneration. Technologic advances in the combination of stem cells, biomaterials, and growth factors have created unique opportunities to fabricate tissues in vivo and in vitro. The therapeutic potential of human multipotent mesenchymal stem cells (MSCs), which are harvested from bone marrow and adipose tissue, has generated increasing interest in a wide variety of biomedical disciplines. These cells can differentiate into a variety of tissue types, including bone, cartilage, fat, and nerve tissue. Adipose-derived stem cells have some advantages compared with other sources of stem cells, most notably that a large number of cells can be easily and quickly isolated from adipose tissue. In current clinical therapy for periodontal tissue regeneration, several methods have been developed and applied either alone or in combination, such as enamel matrix proteins, guided tissue regeneration, autologous/allogeneic/xenogeneic bone grafts, and growth factors. However, there are various limitations and shortcomings for periodontal tissue regeneration using current methods. Recently, periodontal tissue regeneration using MSCs has been examined in some animal models. This method has potential in the regeneration of functional periodontal tissues because the various secreted growth factors from MSCs might not only promote the regeneration of periodontal tissue but also encourage neovascularization of the damaged tissues. Adipose-derived stem cells are especially effective for neovascularization compared with other MSC sources. In this review, the possibility and potential of adipose-derived stem cells for regenerative medicine are introduced. Of particular interest, periodontal tissue regeneration with adipose-derived stem cells is discussed.

  13. The adipose tissue in farm animals: a proteomic approach.

    Science.gov (United States)

    Sauerwein, Helga; Bendixen, Emoke; Restelli, Laura; Ceciliani, Fabrizio

    2014-03-01

    Adipose tissue is not only a tissue where energy is stored but is also involved in regulating several body functions such as appetite and energy expenditure via its endocrine activity. Moreover, it thereby modulates complex processes like reproduction, inflammation and immune response. The products secreted from adipose tissue comprise hormones and cytokines that are collectively termed as adipocytokines or "adipokines"; the discovery and characterization of new proteins secreted by adipose tissue is still ongoing and their number is thus increasing. Adipokines act in both endocrine manner as well as locally, as autocrine or paracrine effectors. Proteomics has emerged as a valuable technique to characterize both cellular and secreted proteomes from adipose tissues, including those of main cellular fractions, i.e. the adipocytes or the stromal vascular fraction containing mainly adipocyte precursors 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 structure for the mammary gland and on its role in participating in and regulating of energy metabolism and other functions. Moreover, as pig has recently become an important model organism to study human diseases, the knowledge of adipose tissue metabolism in pig is relevant for the study of obesity 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

  14. IL-1 family members in the pathogenesis and treatment of metabolic disease: Focus on adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Ballak, Dov B; Stienstra, Rinke; Tack, Cees J; Dinarello, Charles A; van Diepen, Janna A

    2015-10-01

    Obesity is characterized by a chronic, low-grade inflammation that contributes to the development of insulin resistance and type 2 diabetes. Cytokines and chemokines produced by immunocompetent cells influence local as well as systemic inflammation and are therefore critical contributors to the pathogenesis of type 2 diabetes. Hence, cytokines that modulate inflammatory responses are emerging as potential targets for intervention and treatment of the metabolic consequences of obesity. The interleukin-1 (IL-1) family of cytokines and receptors are key mediators of innate inflammatory responses and exhibit both pro- and anti-inflammatory functions. During the last decades, mechanistic insights into how the IL-1 family affects the initiation and progression of obesity-induced insulin resistance have increased significantly. Here, we review the current knowledge and understanding, with emphasis on the therapeutic potential of individual members of the IL-1 family of cytokines for improving insulin sensitivity in patients with diabetes.

  15. Adipose tissue and adipocytes supports tumorigenesis and metastasis#

    OpenAIRE

    Nieman, Kristin M; Romero, Iris L.; Van Houten, Bennett; Lengyel, Ernst

    2013-01-01

    Adipose tissue influences tumor development in two major ways. First, obese individuals have a higher risk of developing certain cancers (endometrial, esophageal, and renal cell cancer). However, the risk of developing other cancers (melanoma, rectal, and ovarian) is not altered by body mass. In obesity, hypertrophied adipose tissue depots are characterized by a state of low grade inflammation. In this activated state, adipocytes and inflammatory cells secrete adipokines and cytokines which a...

  16. (Brown) adipose tissue associated metabolic dysfunction and risk of cardiovascular disease in high risk patients

    NARCIS (Netherlands)

    Franssens, BT

    2016-01-01

    In this thesis it was shown that (brown) adipose tissue associated metabolic dysfunction increases the risk on development of cardiovascular disease in high risk patients. Quantity of adipose tissue is an important risk factor for adipose tissue dysfunction but functionality of adipose tissue not so

  17. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI.

    Science.gov (United States)

    Khan, Tayeba; Muise, Eric S; Iyengar, Puneeth; Wang, Zhao V; Chandalia, Manisha; Abate, Nicola; Zhang, Bei B; Bonaldo, Paolo; Chua, Streamson; Scherer, Philipp E

    2009-03-01

    Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating "adipose tissue fibrosis" as a hallmark of metabolically challenged adipocytes. Collagen VI is a highly enriched extracellular matrix component of adipose tissue. The absence of collagen VI results in the uninhibited expansion of individual adipocytes and is paradoxically associated with substantial improvements in whole-body energy homeostasis, both with high-fat diet exposure and in the ob/ob background. Collectively, our data suggest that weakening the extracellular scaffold of adipocytes enables their stress-free expansion during states of positive energy balance, which is consequently associated with an improved inflammatory profile. Therefore, the disproportionate accumulation of extracellular matrix components in adipose tissue may not be merely an epiphenomenon of metabolically challenging conditions but may also directly contribute to a failure to expand adipose tissue mass during states of excess caloric intake.

  18. Exercise and Adipose Tissue Macrophages: New Frontiers in Obesity Research?

    Science.gov (United States)

    Goh, Jorming; Goh, Kian Peng; Abbasi, Asghar

    2016-01-01

    Obesity is a major public health problem in the twenty-first century. Mutations in genes that regulate substrate metabolism, subsequent dysfunction in their protein products, and other factors, such as increased adipose tissue inflammation, are some underlying etiologies of this disease. Increased inflammation in the adipose tissue microenvironment is partly mediated by the presence of cells from the innate and adaptive immune system. A subset of the innate immune population in adipose tissue include macrophages, termed adipose tissue macrophages (ATMs), which are central players in adipose tissue inflammation. Being extremely plastic, their responses to diverse molecular signals in the microenvironment dictate their identity and functional properties, where they become either pro-inflammatory (M1) or anti-inflammatory (M2). Endurance exercise training exerts global anti-inflammatory responses in multiple organs, including skeletal muscle, liver, and adipose tissue. The purpose of this review is to discuss the different mechanisms that drive ATM-mediated inflammation in obesity and present current evidence of how exercise training, specifically endurance exercise training, modulates the polarization of ATMs from an M1 to an M2 anti-inflammatory phenotype.

  19. Endoplasmic reticulum stress in adipose tissue augments lipolysis.

    Science.gov (United States)

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

    2015-01-01

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

  20. Gene Expression Signature in Adipose Tissue of Acromegaly Patients

    Science.gov (United States)

    Hochberg, Irit; Tran, Quynh T.; Barkan, Ariel L.; Saltiel, Alan R.; Chandler, William F.; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly. PMID:26087292

  1. Gene Expression Signature in Adipose Tissue of Acromegaly Patients.

    Science.gov (United States)

    Hochberg, Irit; Tran, Quynh T; Barkan, Ariel L; Saltiel, Alan R; Chandler, William F; Bridges, Dave

    2015-01-01

    To study the effect of chronic excess growth hormone on adipose tissue, we performed RNA sequencing in adipose tissue biopsies from patients with acromegaly (n = 7) or non-functioning pituitary adenomas (n = 11). The patients underwent clinical and metabolic profiling including assessment of HOMA-IR. Explants of adipose tissue were assayed ex vivo for lipolysis and ceramide levels. Patients with acromegaly had higher glucose, higher insulin levels and higher HOMA-IR score. We observed several previously reported transcriptional changes (IGF1, IGFBP3, CISH, SOCS2) that are known to be induced by GH/IGF-1 in liver but are also induced in adipose tissue. We also identified several novel transcriptional changes, some of which may be important for GH/IGF responses (PTPN3 and PTPN4) and the effects of acromegaly on growth and proliferation. Several differentially expressed transcripts may be important in GH/IGF-1-induced metabolic changes. Specifically, induction of LPL, ABHD5, and NRIP1 can contribute to enhanced lipolysis and may explain the elevated adipose tissue lipolysis in acromegalic patients. Higher expression of TCF7L2 and the fatty acid desaturases FADS1, FADS2 and SCD could contribute to insulin resistance. Ceramides were not different between the two groups. In summary, we have identified the acromegaly gene expression signature in human adipose tissue. The significance of altered expression of specific transcripts will enhance our understanding of the metabolic and proliferative changes associated with acromegaly.

  2. Treatment of micro air bubbles in rat adipose tissue at 25 kPa altitude exposures with perfluorocarbon emulsions and nitric oxide

    DEFF Research Database (Denmark)

    Randsøe, Thomas; Hyldegaard, O

    2014-01-01

    . The effect is ascribed to an increased solubility and transport capacity of respiratory gases in the PFC emulsion and possibly enhanced nitrogen washout through NO-increased blood flow rate and/or the removal of endothelial micro bubble nuclei precursors. Previous reports have shown that metabolic gases (i...... of nitrogen, or in contrast (2) promote bubble growth and stabilization through an increased oxygen supply. METHODS: In anesthetized rats, micro air bubbles (containing 79% nitrogen) of 4-500 nl were injected into exposed abdominal adipose tissue. Rats were decompressed in 36 min to 25 kPa (~10,376 m above...

  3. Adipose Natural Killer Cells Regulate Adipose Tissue Macrophages to Promote Insulin Resistance in Obesity.

    Science.gov (United States)

    Lee, Byung-Cheol; Kim, Myung-Sunny; Pae, Munkyong; Yamamoto, Yasuhiko; Eberlé, Delphine; Shimada, Takeshi; Kamei, Nozomu; Park, Hee-Sook; Sasorith, Souphatta; Woo, Ju Rang; You, Jia; Mosher, William; Brady, Hugh J M; Shoelson, Steven E; Lee, Jongsoon

    2016-04-12

    Obesity-induced inflammation mediated by immune cells in adipose tissue appears to participate in the pathogenesis of insulin resistance. We show that natural killer (NK) cells in adipose tissue play an important role. High-fat diet (HFD) increases NK cell numbers and the production of proinflammatory cytokines, notably TNFα, in epididymal, but not subcutaneous, fat depots. When NK cells were depleted either with neutralizing antibodies or genetic ablation in E4bp4(+/-) mice, obesity-induced insulin resistance improved in parallel with decreases in both adipose tissue macrophage (ATM) numbers, and ATM and adipose tissue inflammation. Conversely, expansion of NK cells following IL-15 administration or reconstitution of NK cells into E4bp4(-/-) mice increased both ATM numbers and adipose tissue inflammation and exacerbated HFD-induced insulin resistance. These results indicate that adipose NK cells control ATMs as an upstream regulator potentially by producing proinflammatory mediators, including TNFα, and thereby contribute to the development of obesity-induced insulin resistance.

  4. Hypertrophy and/or Hyperplasia: Dynamics of Adipose Tissue Growth.

    Science.gov (United States)

    Jo, Junghyo; Gavrilova, Oksana; Pack, Stephanie; Jou, William; Mullen, Shawn; Sumner, Anne E; Cushman, Samuel W; Periwal, Vipul

    2009-03-01

    Adipose tissue grows by two mechanisms: hyperplasia (cell number increase) and hypertrophy (cell size increase). Genetics and diet affect the relative contributions of these two mechanisms to the growth of adipose tissue in obesity. In this study, the size distributions of epididymal adipose cells from two mouse strains, obesity-resistant FVB/N and obesity-prone C57BL/6, were measured after 2, 4, and 12 weeks under regular and high-fat feeding conditions. The total cell number in the epididymal fat pad was estimated from the fat pad mass and the normalized cell-size distribution. The cell number and volume-weighted mean cell size increase as a function of fat pad mass. To address adipose tissue growth precisely, we developed a mathematical model describing the evolution of the adipose cell-size distributions as a function of the increasing fat pad mass, instead of the increasing chronological time. Our model describes the recruitment of new adipose cells and their subsequent development in different strains, and with different diet regimens, with common mechanisms, but with diet- and genetics-dependent model parameters. Compared to the FVB/N strain, the C57BL/6 strain has greater recruitment of small adipose cells. Hyperplasia is enhanced by high-fat diet in a strain-dependent way, suggesting a synergistic interaction between genetics and diet. Moreover, high-fat feeding increases the rate of adipose cell size growth, independent of strain, reflecting the increase in calories requiring storage. Additionally, high-fat diet leads to a dramatic spreading of the size distribution of adipose cells in both strains; this implies an increase in size fluctuations of adipose cells through lipid turnover.

  5. Adipose tissue, the skeleton and cardiovascular disease

    Energy Technology Data Exchange (ETDEWEB)

    Wiklund, Peder

    2011-07-01

    Cardiovascular disease (CVD) is the leading cause of death in the Western World, although the incidence of myocardial infarction (MI) has declined over the last decades. However, obesity, which is one of the most important risk factors for CVD, is increasingly common. Osteoporosis is also on the rise because of an aging population. Based on considerable overlap in the prevalence of CVD and osteoporosis, a shared etiology has been proposed. Furthermore, the possibility of interplay between the skeleton and adipose tissue has received increasing attention the last few years with the discovery that leptin can influence bone metabolism and that osteocalcin can influence adipose tissue. A main aim of this thesis was to investigate the effects of fat mass distribution and bone mineral density on the risk of MI. Using dual-energy x-ray absorptiometry (DEXA) we measured 592 men and women for regional fat mass in study I. In study II this was expanded to include 3258 men and women. In study III 6872 men and women had their bone mineral density measured in the total hip and femoral neck using DEXA. We found that a fat mass distribution with a higher proportion of abdominal fat mass was associated with both an adverse risk factor profile and an increased risk of MI. In contrast, a higher gynoid fat mass distribution was associated with a more favorable risk factor profile and a decreased risk of MI, highlighting the different properties of abdominal and gynoid fat depots (study I-II). In study III, we investigated the association of bone mineral density and risk factors shared between CVD and osteoporosis, and risk of MI. We found that lower bone mineral density was associated with hypertension, and also tended to be associated to other CVD risk factors. Low bone mineral density was associated with an increased risk of MI in both men and women, apparently independently of the risk factors studied (study III). In study IV, we investigated 50 healthy, young men to determine if

  6. Long-acting glucose-dependent insulinotropic polypeptide ameliorates obesity-induced adipose tissue inflammation.

    Science.gov (United States)

    Varol, Chen; Zvibel, Isabel; Spektor, Lior; Mantelmacher, Fernanda Dana; Vugman, Milena; Thurm, Tamar; Khatib, Marian; Elmaliah, Elinor; Halpern, Zamir; Fishman, Sigal

    2014-10-15

    Obesity induces low-grade chronic inflammation, manifested by proinflammatory polarization of adipose tissue innate and adaptive resident and recruited immune cells that contribute to insulin resistance (IR). The glucose-dependent insulinotropic polypeptide (GIP) is an incretin hormone that mediates postprandial insulin secretion and has anabolic effects on the adipose tissue. Importantly, recent evidence suggested that GIP is a potential suppressor of inflammation in several metabolic models. In this study, we aimed to investigate the immunoregulatory role of GIP in a murine model of diet-induced obesity (DIO) using the long-acting GIP analog [d-Ala(2)]GIP. Administration of [d-Ala(2)]GIP resulted in adipocytes of increased size, increased levels of adipose tissue lipid droplet proteins, indicating better lipid storage capacity, and reduced adipose tissue inflammation. Flow cytometry analysis revealed reduced numbers of inflammatory Ly6C(hi) monocytes and F4/80(hi)CD11c(+) macrophages, associated with IR. In addition, [d-Ala(2)]GIP reduced adipose tissue infiltration of IFN-γ-producing CD8(+) and CD4(+) T cells. Furthermore, [d-Ala(2)]GIP treatment induced a favorable adipose tissue adipokine profile, manifested by a prominent reduction in key inflammatory cytokines (TNF-α, IL-1β, IFN-γ) and chemokines (CCL2, CCL8, and CCL5) and an increase in adiponectin. Notably, [d-Ala(2)]GIP also reduced the numbers of circulating neutrophils and proinflammatory Ly6C(hi) monocytes in mice fed regular chow or a high-fat diet. Finally, the beneficial immune-associated effects were accompanied by amelioration of IR and improved insulin signaling in liver and adipose tissue. Collectively, our results describe key beneficial immunoregulatory properties for GIP in DIO and reveal that its augmentation ameliorates adipose tissue inflammation and improves IR. Copyright © 2014 by The American Association of Immunologists, Inc.

  7. Soya protein attenuates abnormalities of the renin-angiotensin system in adipose tissue from obese rats.

    Science.gov (United States)

    Frigolet, María E; Torres, Nimbe; Tovar, Armando R

    2012-01-01

    Several metabolic disturbances during obesity are associated with adipose tissue-altered functions. Adipocytes contain the renin-angiotensin system (RAS), which regulates signalling pathways that control angiogenesis via Akt in an autocrine fashion. Soya protein (Soy) consumption modifies the gene expression pattern in adipose tissue, resulting in an improved adipocyte function. Therefore, the aim of the present work is to study whether dietary Soy regulates the expression of RAS and angiogenesis-related genes and its association with the phosphorylated state of Akt in the adipose tissue of obese rats. Animals were fed a 30 % Soy or casein (Cas) diet containing 5 or 25 % fat for 160 d. mRNA abundance was studied in the adipose tissue, and Akt phosphorylation and hormone release were measured in the primary adipocyte culture. The present results show that Soy treatment in comparison with Cas consumption induces lower angiotensin release and increased insulin-stimulated Akt activation in adipocytes. Furthermore, Soy consumption varies the expression of RAS and angiogenesis-related genes, which maintain cell size and vascularity in the adipose tissue of rats fed a high-fat diet. Thus, adipocyte hypertrophy and impaired angiogenesis, which are frequently observed in dysfunctional adipose tissue, were avoided by consuming dietary Soy. Taken together, these findings suggest that Soy can be used as a dietary strategy to preserve adipocyte functionality and to prevent obesity abnormalities.

  8. Effects of endurance exercise training, metformin, and their combination on adipose tissue leptin and IL-10 secretion in OLETF rats.

    Science.gov (United States)

    Jenkins, Nathan T; Padilla, Jaume; Arce-Esquivel, Arturo A; Bayless, David S; Martin, Jeffrey S; Leidy, Heather J; Booth, Frank W; Rector, R Scott; Laughlin, M Harold

    2012-12-15

    Adipose tissue inflammation plays a role in cardiovascular (CV) and metabolic diseases associated with obesity, insulin resistance, and type 2 diabetes mellitus (T2DM). The interactive effects of exercise training and metformin, two first-line T2DM treatments, on adipose tissue inflammation are not known. Using the hyperphagic, obese, insulin-resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rat model, we tested the hypothesis that treadmill training, metformin, or a combination of these reduces the secretion of proinflammatory cytokines from adipose tissue. Compared with Long-Evans Tokushima Otsuka (LETO) control rats (L-Sed), sedentary OLETF (O-Sed) animals secreted significantly greater amounts of leptin from retroperitoneal adipose tissue. Conversely, secretion of interleukin (IL)-10 by O-Sed adipose tissue was lower than that in L-Sed animals. Examination of leptin and IL-10 secretion from adipose tissue in OLETF groups treated with endurance exercise training (O-EndEx), metformin treatment (O-Met), and a combination of these (O-E+M) from 20 to 32 wk of age indicated that 1) leptin secretion from adipose tissue was reduced in O-Met and O-E+M, but not O-EndEx animals; 2) adipose tissue IL-10 secretion was increased in O-EndEx and O-E+M but not in O-Met animals; and 3) only the combined treatment (O-E+M) displayed both a reduction in leptin secretion and an increase in IL-10 secretion. Leptin and IL-10 concentrations in adipose tissue-conditioned buffers were correlated with their plasma concentrations, adipocyte diameters, and total adiposity. Overall, this study indicates that exercise training and metformin have additive influences on adipose tissue secretion and plasma concentrations of leptin and IL-10.

  9. Ghrelin receptor regulates adipose tissue inflammation in aging.

    Science.gov (United States)

    Lin, Ligen; Lee, Jong Han; Buras, Eric D; Yu, Kaijiang; Wang, Ruitao; Smith, C Wayne; Wu, Huaizhu; Sheikh-Hamad, David; Sun, Yuxiang

    2016-01-01

    Aging is commonly associated with low-grade adipose inflammation, which is closely linked to insulin resistance. Ghrelin is the only circulating orexigenic hormone which is known to increase obesity and insulin resistance. We previously reported that the expression of the ghrelin receptor, growth hormone secretagogue receptor (GHS-R), increases in adipose tissues during aging, and old Ghsr(-/-) mice exhibit a lean and insulin-sensitive phenotype. Macrophages are major mediators of adipose tissue inflammation, which consist of pro-inflammatory M1 and anti-inflammatory M2 subtypes. Here, we show that in aged mice, GHS-R ablation promotes macrophage phenotypical shift toward anti-inflammatory M2. Old Ghsrp(-/-) mice have reduced macrophage infiltration, M1/M2 ratio, and pro-inflammatory cytokine expression in white and brown adipose tissues. We also found that peritoneal macrophages of old Ghsrp(-/-) mice produce higher norepinephrine, which is in line with increased alternatively-activated M2 macrophages. Our data further reveal that GHS-R has cell-autonomous effects in macrophages, and GHS-R antagonist suppresses lipopolysaccharide (LPS)-induced inflammatory responses in macrophages. Collectively, our studies demonstrate that ghrelin signaling has an important role in macrophage polarization and adipose tissue inflammation during aging. GHS-R antagonists may serve as a novel and effective therapeutic option for age-associated adipose tissue inflammation and insulin resistance.

  10. From neutrophils to macrophages: differences in regional adipose tissue depots.

    Science.gov (United States)

    Dam, V; Sikder, T; Santosa, S

    2016-01-01

    Currently, we do not fully understand the underlying mechanisms of how regional adiposity promotes metabolic dysregulation. As adipose tissue expands, there is an increase in chronic systemic low-grade inflammation due to greater infiltration of immune cells and production of cytokines. This chronic inflammation is thought to play a major role in the development of metabolic complications and disease such as insulin resistance and diabetes. We know that different adipose tissue depots contribute differently to the risk of metabolic disease. People who have an upper body fat distribution around the abdomen are at greater risk of disease than those who tend to store fat in their lower body around the hips and thighs. Thus, it is conceivable that adipose tissue depots contribute differently to the inflammatory milieu as a result of varied infiltration of immune cell types. In this review, we describe the role and function of major resident immune cells in the development of adipose tissue inflammation and discuss their regional differences in the context of metabolic disease risk. We find that although initial studies have found regional differences, a more comprehensive understanding of how immune cells interrupt adipose tissue homeostasis is needed.

  11. Cold-induced changes in gene expression in brown adipose tissue, white adipose tissue and liver.

    Directory of Open Access Journals (Sweden)

    Andrew M Shore

    Full Text Available Cold exposure imposes a metabolic challenge to mammals that is met by a coordinated response in different tissues to prevent hypothermia. This study reports a transcriptomic analysis in brown adipose tissue (BAT, white adipose (WAT and liver of mice in response to 24 h cold exposure at 8°C. Expression of 1895 genes were significantly (P<0.05 up- or down-regulated more than two fold by cold exposure in all tissues but only 5 of these genes were shared by all three tissues, and only 19, 14 and 134 genes were common between WAT and BAT, WAT and liver, and BAT and liver, respectively. We confirmed using qRT-PCR, the increased expression of a number of characteristic BAT genes during cold exposure. In both BAT and the liver, the most common direction of change in gene expression was suppression (496 genes in BAT and 590 genes in liver. Gene ontology analysis revealed for the first time significant (P<0.05 down regulation in response to cold, of genes involved in oxidoreductase activity, lipid metabolic processes and protease inhibitor activity, in both BAT and liver, but not WAT. The results reveal an unexpected importance of down regulation of cytochrome P450 gene expression and apolipoprotein, in both BAT and liver, but not WAT, in response to cold exposure. Pathway analysis suggests a model in which down regulation of the nuclear transcription factors HNF4α and PPARα in both BAT and liver may orchestrate the down regulation of genes involved in lipoprotein and steroid metabolism as well as Phase I enzymes belonging to the cytochrome P450 group in response to cold stress in mice. We propose that the response to cold stress involves decreased gene expression in a range of cellular processes in order to maximise pathways involved in heat production.

  12. Hypothalamic regulation of brown adipose tissue thermogenesis and energy homeostasis

    Directory of Open Access Journals (Sweden)

    Wei eZhang

    2015-08-01

    Full Text Available Obesity and diabetes are increasing at an alarming rate worldwide, but the strategies for the prevention and treatment of these disorders remain inadequate. Brown adipose tissue (BAT is important for cold protection by producing heat using lipids and glucose as metabolic fuels. This thermogenic action causes increased energy expenditure and significant lipid/glucose disposal. In addition, BAT in white adipose tissue (WAT or beige cells have been found and they also exhibit the thermogenic action similar to BAT. These data provide evidence indicating BAT/beige cells as a potential target for combating obesity and diabetes. Recent discoveries of active BAT and beige cells in adult humans have further highlighted this potential. Growing studies have also shown the importance of central nervous system in the control of BAT thermogenesis and WAT browning using animal models. This review is focused on central neural thermoregulation, particularly addressing our current understanding of the importance of hypothalamic neural signaling in the regulation of BAT/beige thermogenesis and energy homeostasis.

  13. Effects of platelet-rich plasma, adipose-derived stem cells, and stromal vascular fraction on the survival of human transplanted adipose tissue.

    Science.gov (United States)

    Kim, Deok-Yeol; Ji, Yi-Hwa; Kim, Deok-Woo; Dhong, Eun-Sang; Yoon, Eul-Sik

    2014-11-01

    Traditional adipose tissue transplantation has unpredictable viability and poor absorption rates. Recent studies have reported that treatment with platelet-rich plasma (PRP), adipose-derived stem cells (ASCs), and stromal vascular fraction (SVF) are related to increased survival of grafted adipose tissue. This study was the first simultaneous comparison of graft survival in combination with PRP, ASCs, and SVF. Adipose tissues were mixed with each other, injected subcutaneously into the back of nude mice, and evaluated at 4, 8, and 12 weeks. Human adipocytes were grossly maintained in the ASCs and SVF mixtures. Survival of the adipose tissues with PRP was observed at 4 weeks and with SVF at 8 and 12 weeks. At 12 weeks, volume reduction in the ASCs and SVF mixtures were 36.9% and 32.1%, respectively, which were significantly different from that of the control group without adjuvant treatment, 51.0%. Neovascular structures were rarely observed in any of the groups. Our results suggest that the technique of adding ASCs or SVF to transplanted adipose tissue might be more effective than the conventional grafting method. An autologous adipose tissue graft in combination with ASCs or SVF may potentially contribute to stabilization of engraftment.

  14. Human periprostatic adipose tissue promotes prostate cancer aggressiveness in vitro

    Directory of Open Access Journals (Sweden)

    Ribeiro Ricardo

    2012-04-01

    Full Text Available Abstract Background Obesity is associated with prostate cancer aggressiveness and mortality. The contribution of periprostatic adipose tissue, which is often infiltrated by malignant cells, to cancer progression is largely unknown. Thus, this study aimed to determine if periprostatic adipose tissue is linked with aggressive tumor biology in prostate cancer. Methods Supernatants of whole adipose tissue (explants or stromal vascular fraction (SVF from paired fat samples of periprostatic (PP and pre-peritoneal visceral (VIS anatomic origin from different donors were prepared and analyzed for matrix metalloproteinases (MMPs 2 and 9 activity. The effects of those conditioned media (CM on growth and migration of hormone-refractory (PC-3 and hormone-sensitive (LNCaP prostate cancer cells were measured. Results We show here that PP adipose tissue of overweight men has higher MMP9 activity in comparison with normal subjects. The observed increased activities of both MMP2 and MMP9 in PP whole adipose tissue explants, likely reveal the contribution of adipocytes plus stromal-vascular fraction (SVF as opposed to SVF alone. MMP2 activity was higher for PP when compared to VIS adipose tissue. When PC-3 cells were stimulated with CM from PP adipose tissue explants, increased proliferative and migratory capacities were observed, but not in the presence of SVF. Conversely, when LNCaP cells were stimulated with PP explants CM, we found enhanced motility despite the inhibition of proliferation, whereas CM derived from SVF increased both cell proliferation and motility. Explants culture and using adipose tissue of PP origin are most effective in promoting proliferation and migration of PC-3 cells, as respectively compared with SVF culture and using adipose tissue of VIS origin. In LNCaP cells, while explants CM cause increased migration compared to SVF, the use of PP adipose tissue to generate CM result in the increase of both cellular proliferation and migration

  15. 17β-Estradiol suppresses visceral adipogenesis and activates brown adipose tissue-specific gene expression.

    Science.gov (United States)

    Al-Qahtani, Saad Misfer; Bryzgalova, Galyna; Valladolid-Acebes, Ismael; Korach-André, Marion; Dahlman-Wright, Karin; Efendić, Suad; Berggren, Per-Olof; Portwood, Neil

    2017-01-01

    Both functional ovaries and estrogen replacement therapy (ERT) reduce the risk of type 2 diabetes (T2D). Understanding the mechanisms underlying the antidiabetic effects of 17β-estradiol (E2) may permit the development of a molecular targeting strategy for the treatment of metabolic disease. This study examines how the promotion of insulin sensitivity and weight loss by E2 treatment in high-fat-diet (HFD)-fed mice involve several anti-adipogenic processes in the visceral adipose tissue. Magnetic resonance imaging (MRI) revealed specific reductions in visceral adipose tissue volume in HFD+E2 mice, compared with HFD mice. This loss of adiposity was associated with diminished visceral adipocyte size and reductions in expression of lipogenic genes, adipokines and of the nuclear receptor nr2c2/tr4. Meanwhile, expression levels of adipose triglyceride lipase/pnpla2 and leptin receptor were increased. As mRNA levels of stat3, a transcription factor involved in brown adipose tissue differentiation, were also increased in visceral adipose, the expression of other brown adipose-specific markers was assessed. Both expression and immunohistochemical staining of ucp-1 were increased, and mRNA levels of dio-2, and of adrβ3, a regulator of ucp-1 expression during the thermogenic response, were increased. Furthermore, expression of cpt-1b, a brown adipose-specific gene involved in fatty acid utilization, was also increased. Methylation studies demonstrated that the methylation status of both dio-2 and adrβ3 was significantly reduced. These results show that improved glycemic control and weight loss due to E2 involve anti-adipogenic mechanisms which include suppressed lipogenesis and augmented fatty acid utilization, and in addition, the activation of brown adipose tissue-specific gene expression in association with E2-dependent epigenetic modifications in these genes.

  16. Tissue engineered bulking agent with adipose-derived stem cells and silk fibroin microspheres for the treatment of intrinsic urethral sphincter deficiency.

    Science.gov (United States)

    Shi, Li Bing; Cai, Hong Xia; Chen, Long Kun; Wu, Yan; Zhu, Shou An; Gong, Xiao Nan; Xia, Ya Xian; Ouyang, Hong Wei; Zou, Xiao Hui

    2014-02-01

    In this study we developed a tissue engineered bulking agent that consisted of adipose-derived stem cells (ADSCs) and silk fibroin microspheres to treat stress urinary incontinence caused by severe intrinsic sphincter deficiency (ISD). ISD models were established by completely transection of the bilateral pudendal nerve (PNT) and confirmed by the decreased leak-point pressure (LPP) and increased lumen area of urethra. Injection of silk fibroin microspheres could recover LPP and lumen area at 4 weeks but its efficacy disappears at 8, 12 weeks. Moreover, it was exciting to find that tissue engineered bulking agent brought long-term efficacy (at 4, 8, 12 weeks post-injection) on the recovery of LPP and lumen area. Concomitantly with the function, tissue engineered bulking agent treated group also improved the urethral sphincter structure as exhibited by better tissue regeneration. The findings showed that silk fibroin microspheres alone could work effectively in short-term, while tissue engineered bulking agent that combined silk fibroin microspheres with ADSCs exhibited promising long-term efficacy. This study developed a new strategy of tissue engineered bulking agent for future ISD therapy.

  17. Adipose tissues differentiated by adipose-derived stemcells harvested from transgenic mice

    Institute of Scientific and Technical Information of China (English)

    LU Feng; GAO Jian-hua; Rei Ogawa; Hiroshi Mizuro; Hiki Hykusoku

    2006-01-01

    Objective: To induce adipocyte differentiation in vitro by adipose-derived stromal cells (ASCs) harvested from transgenic mice with green fluorescent protein (GFP)and assess the possibility of constructing adipose tissues via attachment of ASCs to type Ⅰ collagen scaffolds.Methods: Inguinal fat pads from GFP transgenic mice were digested by enzymes for isolation of ASCs (primary culture). After expansion to three passages of ASCs, the cells were incubated in an adipogenic medium for two weeks, and the adipocyte differentiation by ASCs in vitro was assessed by morphological observation and Oil Red O staining. Then they were attached to collagen scaffolds and co-cultured for 12 hours, followed by hypodermic implantation to the dorsal skin of nude mice for 2 months. The newly-formed tissues were detected by HE staining.Results: The cultured primary stem cells were fibroblast-like and showed active proliferation. After being incubated in an adipocyte differentiation medium, the lipid droplets in the cytoplasm accumulated gradually and finally developed into mature adipocytes, which showed positive in Oil Red O staining. A 0.5-cm3 new tissue clot was found under the dorsal skin of the nude mice and it was confirmed as mature adipose tissues by fluorescent observation and HE staining.Conclusions: ASCs can successfully differentiate adipose tissues into mature adipocytes, which exhibit an adipocyte-like morphology and express as intracytoplasmic lipid droplets. It is an efficient model of adipose tissues engineered with ASCs and type Ⅰ collagen scaffolds.

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

    Science.gov (United States)

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

    2015-03-01

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

  19. Under the Surface of Subcutaneous Adipose Tissue Biology.

    Science.gov (United States)

    Pandžić Jakšić, Vlatka; Grizelj, Danijela

    2016-12-01

    The global obesity epidemic enhanced contemporary interest in adipose tissue biology. Two structurally and functionally distinct depots, subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT), are spread throughout the body. Their distribution was recognized to be a major determinant of metabolic risk. Unlike VAT, SAT showed some protective endocrine and inflammatory features that might explain the occurrence of obese but metabolically healthy persons. The unique developmental gene expression signature, angiogenesis, and adipogenic potential of SAT determines its growth ability under the positive energy balance. The overflow hypothesis suggested that when SAT is unable to expand sufficiently, fat overflows towards metabolically adverse ectopic depots. Besides white adipose tissue, recent studies found important brown adipose tissue activity responsible for thermogenesis and energy dissipation in adults as well. SAT is prone to "browning" - the appearance of particular beige adipocytes that contribute to its favorable metabolic effects. Morbid obesity, aging, hormonal status, nutrition, low physical activity, and other environmental factors impair SAT relative resistance to dysfunctional changes and promote development of metabolic disorders. The popular approach considering SAT mainly as the subject of cosmetic procedures for improving the appearance of body contours should be avoided. Complex heterogeneity of obesity revealed that a tissue of an extreme plasticity and rich interactions with vital functions of the body lies under the surface. Therapeutic manipulations to preserve and enhance healthier fat in order to correct obesity-related metabolic disorders seem to be a relevant but still unexplored opportunity.

  20. High intensity interval training improves liver and adipose tissue insulin sensitivity

    Directory of Open Access Journals (Sweden)

    Katarina Marcinko

    2015-12-01

    Conclusions: These data indicate that HIIT lowers blood glucose levels by improving adipose and liver insulin sensitivity independently of changes in adiposity, adipose tissue inflammation, liver lipid content or AMPK phosphorylation of ACC.

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

    OpenAIRE

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

    2015-01-01

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

  2. Adipose tissue, obesity and adipokines: role in cancer promotion.

    Science.gov (United States)

    Booth, Andrea; Magnuson, Aaron; Fouts, Josephine; Foster, Michelle

    2015-01-01

    Adipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose - elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of well-characterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

  3. Natural killer T cells in adipose tissue prevent insulin resistance.

    Science.gov (United States)

    Schipper, Henk S; Rakhshandehroo, Maryam; van de Graaf, Stan F J; Venken, Koen; Koppen, Arjen; Stienstra, Rinke; Prop, Serge; Meerding, Jenny; Hamers, Nicole; Besra, Gurdyal; Boon, Louis; Nieuwenhuis, Edward E S; Elewaut, Dirk; Prakken, Berent; Kersten, Sander; Boes, Marianne; Kalkhoven, Eric

    2012-09-01

    Lipid overload and adipocyte dysfunction are key to the development of insulin resistance and can be induced by a high-fat diet. CD1d-restricted invariant natural killer T (iNKT) cells have been proposed as mediators between lipid overload and insulin resistance, but recent studies found decreased iNKT cell numbers and marginal effects of iNKT cell depletion on insulin resistance under high-fat diet conditions. Here, we focused on the role of iNKT cells under normal conditions. We showed that iNKT cell-deficient mice on a low-fat diet, considered a normal diet for mice, displayed a distinctive insulin resistance phenotype without overt adipose tissue inflammation. Insulin resistance was characterized by adipocyte dysfunction, including adipocyte hypertrophy, increased leptin, and decreased adiponectin levels. The lack of liver abnormalities in CD1d-null mice together with the enrichment of CD1d-restricted iNKT cells in both mouse and human adipose tissue indicated a specific role for adipose tissue-resident iNKT cells in the development of insulin resistance. Strikingly, iNKT cell function was directly modulated by adipocytes, which acted as lipid antigen-presenting cells in a CD1d-mediated fashion. Based on these findings, we propose that, especially under low-fat diet conditions, adipose tissue-resident iNKT cells maintain healthy adipose tissue through direct interplay with adipocytes and prevent insulin resistance.

  4. Adipose tissue as an immunological organ : implications for childhood obesity

    NARCIS (Netherlands)

    Schipper, H.S.

    2013-01-01

    Obesity is increasingly considered as an inflammatory disorder. In adults, obesity induces inflammation of adipose tissue (AT). Through the release of inflammatory lipids and immune mediating proteins called adipokines, AT inflammation spreads to other tissues ranging from liver and muscle to the

  5. Regulation of brown adipose tissue by stress and sex

    NARCIS (Netherlands)

    J.C. van den Beukel (Anneke)

    2016-01-01

    textabstractDue to the increasing incidence of obesity, more means of treating obesity are necessary. Brown adipose tissue (BAT) is a potential target tissue via which obesity can be treated due to its unique ability to use energy to produce heat. Not much is known however about the mechanisms via w

  6. Regulation of brown adipose tissue by stress and sex

    NARCIS (Netherlands)

    J.C. van den Beukel (Anneke)

    2016-01-01

    textabstractDue to the increasing incidence of obesity, more means of treating obesity are necessary. Brown adipose tissue (BAT) is a potential target tissue via which obesity can be treated due to its unique ability to use energy to produce heat. Not much is known however about the mechanisms via w

  7. NPY antagonism reduces adiposity and attenuates age-related imbalance of adipose tissue metabolism.

    Science.gov (United States)

    Park, Seongjoon; Fujishita, Chika; Komatsu, Toshimitsu; Kim, Sang Eun; Chiba, Takuya; Mori, Ryoichi; Shimokawa, Isao

    2014-12-01

    An orexigenic hormone, neuropeptide Y (NPY), plays a role not only in the hypothalamic regulation of appetite, but also in the peripheral regulation of lipid metabolism. However, the intracellular mechanisms triggered by NPY to regulate lipid metabolism are poorly understood. Here we report that NPY deficiency reduces white adipose tissue (WAT) mass and ameliorates the age-related imbalance of adipose tissue metabolism in mice. Gene expression involved in adipogenesis/lipogenesis was found to decrease, whereas proteins involved in lipolysis increased in gonadal WAT (gWAT) of NPY-knockout mice. These changes were associated with an activated SIRT1- and PPARγ-mediated pathway. Moreover, the age-related decrease of de novo lipogenesis in gWAT and thermogenesis in inguinal WAT was inhibited by NPY deficiency. Further analysis using 3T3-L1 cells showed that NPY inhibited lipolysis through the Y1 receptor and enhanced lipogenesis following a reduction in cAMP response element-binding protein (CREB) and SIRT1 protein expression. Therefore, NPY appears to act as a key regulator of adipose tissue metabolism via the CREB-SIRT1 signaling pathway. Taken together, NPY deficiency reduces adiposity and ameliorates the age-related imbalance of adipose tissue metabolism, suggesting that antagonism of NPY may be a promising target for drug development to prevent age-related metabolic diseases.

  8. 11-Beta hydroxysteroid dehydrogenase type 2 expression in white adipose tissue is strongly correlated with adiposity.

    Science.gov (United States)

    Milagro, Fermin I; Campión, Javier; Martínez, J Alfredo

    2007-04-01

    Glucocorticoid action within the cells is regulated by the levels of glucocorticoid receptor (GR) expression and two enzymes, 11-beta hydroxysteroid dehydrogenase type 1 (11betaHSD1), which converts inactive to active glucocorticoids, and 11-beta hydroxysteroid dehydrogenase type 2 (11betaHSD2), which regulates the access of active glucocorticoids to the receptor by converting cortisol/corticosterone to the glucocorticoid-inactive form cortisone/dehydrocorticosterone. Male Wistar rats developed obesity by being fed a high-fat diet for 56 days, and GR, 11betaHSD1 and 11betaHSD2 gene expression were compared with control-diet fed animals. Gene expression analysis of 11betaHSD1, 11betaHSD2 and GR were performed by RT-PCR in subcutaneous and retroperitoneal adipose tissue. High-fat fed animals overexpressed 11betaHSD2 in subcutaneous but not in retroperitoneal fat. Interestingly, mRNA levels strongly correlated in both tissues with different parameters related to obesity, such as body weight, adiposity and insulin resistance, suggesting that this gene is a reliable marker of adiposity in this rat model of obesity. Thus, 11betaHSD2 is expressed in adipose tissue by both adipocytes and stromal-vascular cells, which suggests that this enzyme may play an important role in preventing fat accumulation in adipose tissue.

  9. 1,25-Dihydroxyvitamin D3 upregulates leptin expression in mouse adipose tissue.

    Science.gov (United States)

    Kong, Juan; Chen, Yunzi; Zhu, Guojun; Zhao, Qun; Li, Yan Chun

    2013-02-01

    Leptin is an adipose tissue-derived hormone that plays a critical role in energy homeostasis. Vitamin D has been shown to regulate energy metabolism, but the relationship between vitamin D and leptin is unclear. Leptin expression and secretion was reduced in vitamin D receptor (VDR)-null mice and increased in transgenic (Tg) mice overexpressing the VDR in adipocytes; however, as leptin is mainly determined by fat mass, it is unclear whether the vitamin D hormone directly regulates leptin expression. To address this question, we determined the effect of vitamin D on leptin expression in vivo and ex vivo. One-week treatment of WT mice with the vitamin D analog RO-27-5646 led to a significant increase in adipose leptin mRNA transcript and serum leptin levels. Moreover, in adipose tissue cultures, 1,25-dihydroxyvitamin D markedly stimulated mRNA expression and secretion of leptin, but not resistin, in adipose tissues obtained from WT mice, but not from VDR-null mice, and leptin upregulation induced by 1,25-dihydroxyvitamin D was more robust in adipose tissues obtained from VDR Tg mice compared with WT mice. These data demonstrate that 1,25-dihydroxyvitamin D stimulates adipose leptin production in a VDR-dependent manner, suggesting that vitamin D may affect energy homeostasis through direct regulation of leptin expression.

  10. Isolation and expansion of adipose-derived stem cells for tissue engineering

    DEFF Research Database (Denmark)

    Fink, Trine; Rasmussen, Jeppe Grøndahl; Lund, Pia

    2011-01-01

    For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs for subseq......For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs...

  11. Bovine dedifferentiated adipose tissue (DFAT) cells

    Science.gov (United States)

    Wei, Shengjuan; Du, Min; Jiang, Zhihua; Duarte, Marcio S; Fernyhough-Culver, Melinda; Albrecht, Elke; Will, Katja; Zan, Linsen; Hausman, Gary J; Elabd, Elham M Youssef; Bergen, Werner G; Basu, Urmila; Dodson, Michael V

    2013-01-01

    Dedifferentiated fat cells (DFAT cells) are derived from lipid-containing (mature) adipocytes, which possess the ability to symmetrically or asymmetrically proliferate, replicate, and redifferentiate/transdifferentiate. Robust cell isolation and downstream culture methods are needed to isolate large numbers of DFAT cells from any (one) adipose depot in order to establish population dynamics and regulation of the cells within and across laboratories. In order to establish more consistent/repeatable methodology here we report on two different methods to establish viable DFAT cell cultures: both traditional cell culture flasks and non-traditional (flat) cell culture plates were used for ceiling culture establishment. Adipocytes (maternal cells of the DFAT cells) were easier to remove from flat culture plates than flasks and the flat plates also allowed cloning rings to be utilized for cell/cell population isolation. While additional aspects of usage of flat-bottomed cell culture plates may yet need to be optimized by definition of optimum bio-coating to enhance cell attachment, utilization of flat plate approaches will allow more efficient study of the dedifferentiation process or the DFAT progeny cells. To extend our preliminary observations, dedifferentiation of Wagyu intramuscular fat (IMF)-derived mature adipocytes and redifferentiation ability of DFAT cells utilizing the aforementioned isolation protocols were examined in traditional basal media/differentiation induction media (DMI) containing adipogenic inducement reagents. In the absence of treatment approximately 10% isolated Wagyu IMF-mature adipocytes dedifferentiated spontaneously and 70% DFAT cells displayed protracted adipogenesis 12 d after confluence in vitro. Lipid-free intracellular vesicles in the cytoplasm (vesicles possessing an intact membrane but with no any observable or stainable lipid inside) were observed during redifferentiation. One to 30% DFAT cells redifferentiated into lipid

  12. Brown adipose tissue in humans: therapeutic potential to combat obesity.

    Science.gov (United States)

    Carey, Andrew L; Kingwell, Bronwyn A

    2013-10-01

    Harnessing the considerable capacity of brown adipose tissue (BAT) to consume energy was first proposed as a potential target to control obesity nearly 40years ago. The plausibility of this approach was, however, questioned due to the prevailing view that BAT was either not present or not functional in adult humans. Recent definitive identification of functional BAT in adult humans as well as a number of important advances in the understanding of BAT biology has reignited interest in BAT as an anti-obesity target. Proof-of-concept evidence demonstrating drug-induced BAT activation provides an important foundation for development of targeted pharmacological approaches with clinical application. This review considers evidence from both human and relevant animal studies to determine whether harnessing BAT for the treatment of obesity via pharmacological intervention is a realistic goal. Copyright © 2013 Elsevier Inc. All rights reserved.

  13. Negative regulators of brown adipose tissue (BAT)-mediated thermogenesis.

    Science.gov (United States)

    Sharma, Bal Krishan; Patil, Mallikarjun; Satyanarayana, Ande

    2014-12-01

    Brown adipose tissue (BAT) is specialized for energy expenditure, a process called adaptive thermogenesis. PET-CT scans recently demonstrated the existence of metabolically active BAT in adult humans, which revitalized our interest in BAT. Increasing the amount and/or activity of BAT holds tremendous promise for the treatment of obesity and its associated diseases. PGC1α is the master regulator of UCP1-mediated thermogenesis in BAT. A number of proteins have been identified to influence thermogenesis either positively or negatively through regulating the expression or transcriptional activity of PGC1α. Therefore, BAT activation can be achieved by either inducing the expression of positive regulators of PGC1α or by inhibiting the repressors of the PGC1α/UCP1 pathway. Here, we review the most important negative regulators of PGC1α/UCP1 signaling and their mechanism of action in BAT-mediated thermogenesis.

  14. Effect of diethylstilboestrol on adipose-tissue lipids.

    Science.gov (United States)

    Sink, J D; Huston, C K; Shigley, J W

    1965-11-01

    1. The effect of diethylstilboestrol on the fatty acid composition of adipose-tissue lipids of the ox (Bos taurus) was studied. 2. The capsula adiposa (perirenal) was shown to contain more total saturated fatty acids, whereas more total unsaturated fatty acids were found in the panniculus adiposus (subcutaneous). 3. Significantly more stearic acid and linolenic acid were obtained from the capsula adiposa, whereas the panniculus adiposus contained more myristoleic acid, palmitoleic acid and oleic acid. 4. Implanting diethylstilboestrol significantly increased the deposition of the saturated fatty acids, particularly stearic acid. 5. A decrease in the deposition of total unsaturated fatty acids, myristoleic acid, palmitoleic acid and linoleic acid can also be attributed to the diethylstilboestrol treatment.

  15. Deletion of Fas in adipocytes relieves adipose tissue inflammation and hepatic manifestations of obesity in mice.

    Science.gov (United States)

    Wueest, Stephan; Rapold, Reto A; Schumann, Desiree M; Rytka, Julia M; Schildknecht, Anita; Nov, Ori; Chervonsky, Alexander V; Rudich, Assaf; Schoenle, Eugen J; Donath, Marc Y; Konrad, Daniel

    2010-01-01

    Adipose tissue inflammation is linked to the pathogenesis of insulin resistance. In addition to exerting death-promoting effects, the death receptor Fas (also known as CD95) can activate inflammatory pathways in several cell lines and tissues, although little is known about the metabolic consequence of Fas activation in adipose tissue. We therefore sought to investigate the contribution of Fas in adipocytes to obesity-associated metabolic dysregulation. Fas expression was markedly increased in the adipocytes of common genetic and diet-induced mouse models of obesity and insulin resistance, as well as in the adipose tissue of obese and type 2 diabetic patients. Mice with Fas deficiency either in all cells or specifically in adipocytes (the latter are referred to herein as AFasKO mice) were protected from deterioration of glucose homeostasis induced by high-fat diet (HFD). Adipocytes in AFasKO mice were more insulin sensitive than those in wild-type mice, and mRNA levels of proinflammatory factors were reduced in white adipose tissue. Moreover, AFasKO mice were protected against hepatic steatosis and were more insulin sensitive, both at the whole-body level and in the liver. Thus, Fas in adipocytes contributes to adipose tissue inflammation, hepatic steatosis, and insulin resistance induced by obesity and may constitute a potential therapeutic target for the treatment of insulin resistance and type 2 diabetes.

  16. MicroRNAs in dysfunctional adipose tissue: cardiovascular implications.

    Science.gov (United States)

    Icli, Basak; Feinberg, Mark W

    2017-07-01

    In this review, we focus on the emerging role of microRNAs, non-coding RNAs that regulate gene expression and signaling pathways, in dysfunctional adipose tissue. We highlight current paradigms of microRNAs involved in adipose differentiation and function in depots such as white, brown, and beige adipose tissues and potential implications of microRNA dysregulation in human disease such as obesity, inflammation, microvasculature dysfunction, and related cardiovascular diseases. We highlight accumulating studies indicating that adipocyte-derived microRNAs may not only serve as biomarkers of cardiometabolic disease, but also may directly regulate gene expression of other tissues. Finally, we discuss the future prospects, challenges, and emerging strategies for microRNA delivery and targeting for therapeutic applications in cardiovascular disease states associated with adipocyte dysfunction. Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2017. For permissions, please email: journals.permissions@oup.com.

  17. The effect of hypokinesia on lipid metabolism in adipose tissue

    Science.gov (United States)

    Macho, Ladislav; Kvetn̆anský, Richard; Ficková, Mária

    The increase of nonesterified fatty acid (NEFA) concentration in plasma was observed in rats subjected to hypokinesia for 1-60 days. In the period of recovery (7 and 21 days after 60 days immobilization) the content of NEFA returned to control values. The increase of fatty acid release from adipose tissue was observed in hypokinetic rats, however the stimulation of lipolysis by norepinephrine was lower in rats exposed to hypokinesis. The decrease of the binding capacity and a diminished number of beta-adrenergic receptors were found in animals after hypokinesia. The augmentation of the incorporation of glucose into lipids and the marked increase in the stimulation of lipogenesis by insulin were found in adipose tissue of rats subjected to long-term hypokinesia. These results showed an important effect of hypokinesia on lipid mobilization, on lipogenesis and on the processes of hormone regulation in adipose tissue.

  18. Adipose tissue Fatty Acid patterns and changes in antrhropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

    2011-01-01

    Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...... in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate...... the associations of adipose tissue fatty acid patterns with changes in weight, waist circumference (WC), and WC controlled for changes in body mass index (WCBMI), adjusting for confounders. Results 7 principal components were extracted for each sex, explaining 77.6% and 78.3% of fatty acid variation in men...

  19. The effects of adipose tissue and adipocytokines in human pregnancy.

    Science.gov (United States)

    Valsamakis, G; Kumar, S; Creatsas, G; Mastorakos, G

    2010-09-01

    During pregnancy, important changes take place in maternal metabolism because of the growing fetus and placental formation. The increase in insulin resistance during pregnancy is paralleled by the progressive increase of maternal adipose tissue deposition. This review examines the topography of fat mass deposition during pregnancy in relation to factors such as parity and maternal age that might affect this deposition. We also examine adipose tissue markers, such as pregravid weight and weight gain during pregnancy, and their effect on fetal growth and pregnancy outcomes. In addition, this review studies the possible effects of cytokines that are produced by adipose tissue and the placenta on maternal metabolism and its complications. Finally, we also consider the possible role of maternal adipocytokines and fetal adipocytokines on fetal growth. © 2010 New York Academy of Sciences.

  20. In vivo Analysis of White Adipose Tissue in Zebrafish

    Science.gov (United States)

    Minchin, James E.N.; Rawls, John F.

    2016-01-01

    White adipose tissue (WAT) is the major site of energy storage in bony vertebrates, and also serves central roles in the endocrine regulation of energy balance. The cellular and molecular mechanisms underlying WAT development and physiology are not well understood. This is due in part to difficulties associated with imaging adipose tissues in mammalian model systems, especially during early life stages. The zebrafish (Danio rerio) has recently emerged as a new model system for adipose tissue research, in which WAT can be imaged in a transparent living vertebrate at all life stages. Here we present detailed methods for labeling adipocytes in live zebrafish using fluorescent lipophilic dyes, and for in vivo microscopy of zebrafish WAT. PMID:21951526

  1. Bovine dedifferentiated adipose tissue (DFAT) cells

    OpenAIRE

    Wei, Shengjuan; Du, Min; Jiang, Zhihua; Duarte, Marcio S.; Fernyhough-Culver, Melinda; Albrecht, Elke; Will, Katja; Zan, Linsen; Hausman, Gary J.; Elabd, Elham M Youssef; Bergen, Werner G.; Basu, Urmila; Dodson, Michael V.

    2013-01-01

    Dedifferentiated fat cells (DFAT cells) are derived from lipid-containing (mature) adipocytes, which possess the ability to symmetrically or asymmetrically proliferate, replicate, and redifferentiate/transdifferentiate. Robust cell isolation and downstream culture methods are needed to isolate large numbers of DFAT cells from any (one) adipose depot in order to establish population dynamics and regulation of the cells within and across laboratories. In order to establish more consistent/repea...

  2. Resistant starch improves insulin resistance and reduces adipose tissue weight and CD11c expression in rat OLETF adipose tissue.

    Science.gov (United States)

    Harazaki, Tomomi; Inoue, Seiya; Imai, Chihiro; Mochizuki, Kazuki; Goda, Toshinao

    2014-05-01

    CD11s/CD18 dimers induce monocyte/macrophage infiltration into many tissues, including adipose tissues. In particular, it was reported that β2-integrin CD11c-positive macrophages in adipose tissues are closely associated with the development of insulin resistance. The aim of this study was to determine whether intake of resistant starch (RS) reduces macrophage accumulation in adipose tissues and inhibits the development of insulin resistance at an early stage in Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Twenty-two-wk-old male OLETF rats were fed a control diet (55% α-corn starch) or an RS diet (55% RS) for 5 wk. An oral glucose tolerance test was performed after 4 wk of feeding; tissues (mesenteric and epididymal adipose tissues, and liver) and tail vein blood were collected after 5 wk of feeding the test diets. Feeding the RS diet to OLETF rats for 5 wk improved insulin resistance, reduced the mesenteric adipose tissue weight, and enhanced the number of small adipocytes. CD68 expression, a macrophage infiltration marker, was not changed by the RS diet, whereas the gene expression levels of integrins such as CD11c, CD11d, and CD18, but not CD11a, and CD11b, were significantly reduced. CD11c protein expression was reduced by the RS diet. These findings suggest that part of the mechanism for the improved insulin resistance by the RS diet involves a reduction of CD11c expression in adipose tissues. Copyright © 2014 Elsevier Inc. All rights reserved.

  3. Different adipose tissue depots: Metabolic implications and effects of surgical removal.

    Science.gov (United States)

    Marcadenti, Aline; de Abreu-Silva, Erlon Oliveira

    2015-11-01

    Increased adiposity has been associated to worse metabolic profile, cardiovascular disease, and mortality. There are two main adipose tissue depots in the body, subcutaneous and visceral adipose tissue, which differ in anatomical location. A large body of evidence has shown the metabolic activity of adipose tissue; lipectomy and/or liposuction therefore appear to be alternatives for improving metabolic profile through rapid loss of adipose tissue. However, surgical removal of adipose tissue may be detrimental for metabolism, because subcutaneous adipose tissue has not been associated to metabolic disorders such as insulin resistance and type 2 diabetes mellitus. In addition, animal studies have shown a compensatory growth of adipose tissue in response to lipectomy. This review summarizes the implications of obesity-induced metabolic dysfunction, its relationship with the different adipose tissue depots, and the effects of lipectomy on cardiometabolic risk factors. Copyright © 2015 SEEN. Published by Elsevier España, S.L.U. All rights reserved.

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

    Institute of Scientific and Technical Information of China (English)

    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

  5. Regional differences and up-regulation of progesterone receptors in adipose tissues from oestrogen-treated sheep.

    Science.gov (United States)

    Mayes, J S; McCann, J P; Ownbey, T C; Watson, G H

    1996-01-01

    Differing risk factors between men and women for a number of vascular and metabolic diseases have been linked to regional obesity. The differences in the distribution of adipose tissues between men (abdominal or upper-body obesity) and women (gluteal/femoral or lower body obesity) suggest a role for sex steroids in the regional distribution of fat. Previous work from this laboratory has shown the presence of oestrogen receptor (ER) in gluteal, perirenal and omental adipose tissues of ewes with similar physical characteristics to the ER in uterine tissue. The concentration profile for adipose ER was gluteal > perirenal > omental. In this report, we determined the physiological significance of adipose ERs by showing an up-regulation of the progesterone receptor (PR) in adipose tissues after oestrogen treatment in a fashion similar to that seen in a major responsive tissue such as uterus. Using PR antibodies (PR-6 and C-262), Western blot analysis of PR from oestrogen-treated sheep indicated that PR was induced in uterus > gluteal adipose > perirenal adipose consistent with the concentration of ER contained in these tissues. PR could not be detected by Western blotting in omental adipose tissue from oestrogen-treated animals or in gluteal, perirenal and omental adipose tissues from untreated animals. Sucrose gradient profiles of progestin (R-5020) binding from uterus and gluteal adipose tissues of oestrogen-treated ewes showed specific binding in both the 5S and 9S regions of the gradient, while perirenal and omental adipose tissue had only the 5S peak. The amount of specific binding was increased with oestrogen treatment in all the tissues. When gluteal adipose tissue cytosol was preincubated with PR antibody (C-262) to prevent binding of ligand and subjected to sucrose gradient analysis, both the 5S and 9S regions were diminished, suggesting that both peaks contained PR. Dilution of uterine cytosol resulted in an increase in the ratio of the 5S to the 9S peak

  6. Adipocyte insulin receptor activity maintains adipose tissue mass and lifespan.

    Science.gov (United States)

    Friesen, Max; Hudak, Carolyn S; Warren, Curtis R; Xia, Fang; Cowan, Chad A

    2016-08-05

    Type 2 diabetes follows a well-defined progressive pathogenesis, beginning with insulin resistance in metabolic tissues such as the adipose. Intracellular signaling downstream of insulin receptor activation regulates critical metabolic functions of adipose tissue, including glucose uptake, lipogenesis, lipolysis and adipokine secretion. Previous studies have used the aP2 promoter to drive Cre recombinase expression in adipose tissue. Insulin receptor (IR) knockout mice created using this aP2-Cre strategy (FIRKO mice) were protected from obesity and glucose intolerance. Later studies demonstrated the promiscuity of the aP2 promoter, casting doubts upon the tissue specificity of aP2-Cre models. It is our goal to use the increased precision of the Adipoq promoter to investigate adipocyte-specific IR function. Towards this end we generated an adipocyte-specific IR knockout (AIRKO) mouse using an Adipoq-driven Cre recombinase. Here we report AIRKO mice are less insulin sensitive throughout life, and less glucose tolerant than wild-type (WT) littermates at the age of 16 weeks. In contrast to WT littermates, the insulin sensitivity of AIRKO mice is unaffected by age or dietary regimen. At any age, AIRKO mice are comparably insulin resistant to old or obese WT mice and have a significantly reduced lifespan. Similar results were obtained when these phenotypes were re-examined in FIRKO mice. We also found that the AIRKO mouse is protected from high-fat diet-induced weight gain, corresponding with a 90% reduction in tissue weight of major adipose depots compared to WT littermates. Adipose tissue mass reduction is accompanied by hepatomegaly and increased hepatic steatosis. These data indicate that adipocyte IR function is crucial to systemic energy metabolism and has profound effects on adiposity, hepatic homeostasis and lifespan. Copyright © 2016. Published by Elsevier Inc.

  7. Chagas disease, adipose tissue and the metabolic syndrome

    Directory of Open Access Journals (Sweden)

    Fnu Nagajyothi

    2009-07-01

    Full Text Available Trypanosoma cruzi infection of the adipose tissue of mice triggers the local expression of inflammatory mediators and a reduction in the expression of the adipokine adiponectin. T. cruzi can be detected in adipose tissue by PCR 300 days post-infection. Infection of cultured adipocytes results in increased expression of cytokines and chemokines and a reduction in the expression of adiponectin and the peroxisome proliferator-activated receptor ³, both of which are negative regulators of inflammation. Infection also results in the upregulation of cyclin D1, the Notch pathway, and extracellular signal-regulated kinase and a reduction in the expression of caveolin-1. Thus, T. cruzi infection of cultured adipocytes leads to an upregulation of the inflammatory process. Since adiponectin null mice have a cardiomyopathic phenotype, it is possible that the reduction in adiponectin contributes to the pathogenesis of chagasic cardiomyopathy. Adipose tissue may serve as a reservoir for T. cruzi from which parasites can become reactivated during periods of immunosuppression. T. cruzi infection of mice often results in hypoglycemia. In contrast, hyperglycemia as observed in diabetes results in increased parasitemia and mortality. Adipose tissue is an important target tissue of T. cruzi and the infection of this tissue is associated with a profound impact on systemic metabolism, increasing the risk of metabolic syndrome.

  8. Osteopontin: Relation between Adipose Tissue and Bone Homeostasis

    Science.gov (United States)

    Messina, Antonietta; Monda, Vincenzo; Viggiano, Emanuela; Valenzano, Anna; Esposito, Teresa; Cibelli, Giuseppe

    2017-01-01

    Osteopontin (OPN) is a multifunctional protein mainly associated with bone metabolism and remodeling. Besides its physiological functions, OPN is implicated in the pathogenesis of a variety of disease states, such as obesity and osteoporosis. Importantly, during the last decades obesity and osteoporosis have become among the main threats to health worldwide. Because OPN is a protein principally expressed in cells with multifaceted effects on bone morphogenesis and remodeling and because it seems to be one of the most overexpressed genes in the adipose tissue of the obese contributing to osteoporosis, this mini review will highlight recent insights about relation between adipose tissue and bone homeostasis.

  9. Adipose tissue Fatty Acid patterns and changes in antrhropometry

    DEFF Research Database (Denmark)

    Dahm, Christina Catherine; Gorst-Rasmussen, Anders; Jakobsen, Marianne Uhre

    2011-01-01

    in adipose tissue fatty acids and changes in anthropometry. Methods 34 fatty acid species from adipose tissue biopsies were determined in a random sample of 1100 men and women from a Danish cohort study. We used sex-specific principal component analysis and multiple linear regression to investigate......Introduction Diets rich in n-3 long chain polyunsaturated fatty acids (LC-PUFA), but low in n-6 LC-PUFA and 18:1 trans-fatty acids (TFA), may lower the risk of overweight and obesity. These fatty acids have often been investigated individually. We explored associations between global patterns...

  10. Natural killer T cells in adipose tissue are activated in lean mice.

    Science.gov (United States)

    Kondo, Taisuke; Toyoshima, Yujiro; Ishii, Yoshiyuki; Kyuwa, Shigeru

    2013-01-01

    Adipose tissues are closely connected with the immune system. It has been suggested that metabolic syndromes such as type 2 diabetes, arteriosclerosis and liver steatosis can be attributed to adipose tissue inflammation characterized by macrophage infiltration. To understand a physiological and pathological role of natural killer T (NKT) cells on inflammation in adipose tissue, we characterized a subset of NKT cells in abdominal and subcutaneous adipose tissues in C57BL/6J mice fed normal or high-fat diets. NKT cells comprised a larger portion of lymphocytes in adipose tissues compared with the spleen and peripheral blood, with epididymal adipose tissue having the highest number of NKT cells. Furthermore, some NKT cells in adipose tissues expressed higher levels of CD69 and intracellular interferon-γ, whereas the Vβ repertoires of NKT cells in adipose tissues were similar to other cells. In obese mice fed a high-fat diet, adipose tissue inflammation had little effect on the Vβ repertoire of NKT cells in epididymal adipose tissues. We speculate that the NKT cells in adipose tissues may form an equivalent subset in other tissues and that these subsets are likely to participate in adipose tissue inflammation. Additionally, the high expression level of CD69 and intracellular IFN-γ raises the possibility that NKT cells in adipose tissue may be stimulated by some physiological mechanism.

  11. Vitamin D and adipose tissue - more than storage

    Directory of Open Access Journals (Sweden)

    Shivaprakash Jagalur Mutt

    2014-06-01

    Full Text Available The pandemic increase in obesity is inversely associated with vitamin D levels. While a higher BMI was causally related to lower 25-hydroxyvitamin D (25(OHD, no evidence was obtained for a BMI lowering effect by higher 25(OHD. Some of the physiological functions of 1,25(OH2D3 (1,25-dihydroxycholecalciferol or calcitriol via its receptor within the adipose tissue have been investigated such as its effect on energy balance, adipogenesis, adipokine and cytokine secretion. Adipose tissue inflammation has been recognized as the key component of metabolic disorders, e.g. in the metabolic syndrome. The adipose organ secretes more than 260 different proteins/peptides. However, the molecular basis of the interactions of 1,25(OH2D3, vitamin D binding proteins (VDBPs and nuclear vitamin D receptor (VDR after sequestration in adipose tissue and their regulations are still unclear. 1,25(OH2D3 and its inactive metabolites are known to inhibit the formation of adipocytes in mouse 3T3-L1 cell line. In humans, 1,25(OH2D3 promotes preadipocyte differentiation under cell culture conditions. Further evidence of its important functions is given by VDR knock out (VDR -/- and CYP27B1 knock out (CYP27B1 -/- mouse models: Both VDR -/- and CYP27B1 -/- models are highly resistant to the diet induced weight gain, while the specific overexpression of human VDR in adipose tissue leads to increased adipose tissue mass. The analysis of microarray datasets from human adipocytes treated with macrophage-secreted products up-regulated VDR and CYP27B1 genes indicating the capacity of adipocytes to even produce active 1,25(OH2D3. Experimental studies demonstrate that 1,25(OH2D3 has an active role in adipose tissue by modulating inflammation, adipogenesis and adipocyte secretion. Yet, further in vivo studies are needed to address the effects and the effective dosages of vitamin D in human adipose tissue and its relevance in the associated diseases.

  12. Telmisartan improves insulin resistance and modulates adipose tissue macrophage polarization in high-fat-fed mice.

    Science.gov (United States)

    Fujisaka, Shiho; Usui, Isao; Kanatani, Yukiko; Ikutani, Masashi; Takasaki, Ichiro; Tsuneyama, Koichi; Tabuchi, Yoshiaki; Bukhari, Agussalim; Yamazaki, Yu; Suzuki, Hikari; Senda, Satoko; Aminuddin, Aminuddin; Nagai, Yoshinori; Takatsu, Kiyoshi; Kobayashi, Masashi; Tobe, Kazuyuki

    2011-05-01

    Diet-induced obesity is reported to induce a phenotypic switch in adipose tissue macrophages from an antiinflammatory M2 state to a proinflammatory M1 state. Telmisartan, an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-γ agonist, reportedly has more beneficial effects on insulin sensitivity than other angiotensin II type 1 receptor blockers. In this study, we studied the effects of telmisartan on the adipose tissue macrophage phenotype in high-fat-fed mice. Telmisartan was administered for 5 wk to high-fat-fed C57BL/6 mice. Insulin sensitivity, macrophage infiltration, and the gene expressions of M1 and M2 markers in visceral adipose tissues were then examined. An insulin- or a glucose-tolerance test showed that telmisartan treatment improved insulin resistance, decreasing the body weight gain, visceral fat weight, and adipocyte size without affecting the amount of energy intake. Telmisartan reduced the mRNA expression of CD11c and TNF-α, M1 macrophage markers, and significantly increased the expressions of M2 markers, such as CD163, CD209, and macrophage galactose N-acetyl-galactosamine specific lectin (Mgl2), in a quantitative RT-PCR analysis. A flow cytometry analysis showed that telmisartan decreased the number of M1 macrophages in visceral adipose tissues. In conclusion, telmisartan improves insulin sensitivity and modulates adipose tissue macrophage polarization to an antiinflammatory M2 state in high-fat-fed mice.

  13. Maternal nutritional manipulations program adipose tissue dysfunction in offspring.

    Science.gov (United States)

    Lecoutre, Simon; Breton, Christophe

    2015-01-01

    Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth) and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates). Maternal nutritional manipulations reprogram offspring's adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids) and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations.

  14. Maternal nutritional manipulations program adipose tissue dysfunction in offspring

    Directory of Open Access Journals (Sweden)

    Simon eLecoutre

    2015-05-01

    Full Text Available Based on the concept of Developmental Origin of Health and Disease, both human and animal studies have demonstrated a close link between nutrient supply perturbations in the fetus or neonate (i.e., maternal undernutrition, obesity, gestational diabetes and/or rapid catch-up growth and increased risk of adult-onset obesity. Indeed, the adipose tissue has been recognized as a key target of developmental programming in a sex-and depot-specific manner. Despite different developmental time windows, similar mechanisms of adipose tissue programming have been described in rodents and in bigger mammals (sheep, primates. Maternal nutritional manipulations reprogram offspring’s adipose tissue resulting in series of alterations: enhanced adipogenesis and lipogenesis, impaired sympathetic activity with reduced noradrenergic innervations and thermogenesis as well as low-grade inflammation. These changes affect adipose tissue development, distribution and composition predisposing offspring to fat accumulation. Modifications of hormonal tissue sensitivity (i.e., leptin, insulin, glucocorticoids and/or epigenetic mechanisms leading to persistent changes in gene expression may account for long-lasting programming across generations.

  15. Ontogenetic development of adipose tissue in grass carp (Ctenopharyngodon idellus).

    Science.gov (United States)

    Liu, Pin; Ji, Hong; Li, Chao; Tian, Jingjing; Wang, Yifei; Yu, Ping

    2015-08-01

    To investigate the adipose tissue development process during the early stages of grass carp (Ctenopharyngodon idellus) development, samples were collected from fertilized eggs to 30 days post-fertilization (dpf) of fish. Paraffin and frozen sections were taken to observe the characteristics of adipocytes in vivo by different staining methods, including hematoxylin and eosin (H&E), Oil red O, and BODIPY. The expression of lipogenesis-related genes of the samples at different time points was detected by real-time qPCR. In addition, protein expression level of peroxisome proliferator-activated receptors γ (PPAR γ) was detected by immunohistochemistry. The results showed that the neutral lipid droplets accumulated first in the hepatocytes of 14-dpf fish larvae, and visceral adipocytes appeared around the hepatopancreas on 16 dpf. As grass carp grew, the adipocytes increased in number and spread to other tissues. In 20-dpf fish larvae, the intestine was observed to be covered by adipose tissue. However, there was no significant change in the average size (30.40-40.01 μm) of adipocytes during this period. Accordingly, the gene expression level of PPAR γ and CCAAT/enhancer-binding proteins α (C/EBP α) was significantly elevated after fertilization for 12 days (p adipose tissue is caused by active recruitment of adipocytes as opposed to hypertrophy of the cell. In addition, our study indicated that lipogenesis-related genes might regulate the ongoing development of adipose tissue.

  16. Regulation of adiponectin gene expression in adipose tissue by thyroid hormones.

    Science.gov (United States)

    Seifi, Samira; Tabandeh, Mohammad Reza; Nazifi, Saed; Saeb, Mehdi; Shirian, Sadegh; Sarkoohi, Parisa

    2012-06-01

    Available experimental data suggest that adiponectin and thyroid hormones have biological interaction in vivo. However, the effects of thyroid hormones on adipose adiponectin gene expression in thyroid dysfunction are unclear. We induced hyper- (HYPER) and hypothyroidism (HYPO) by daily administration of a 12 mg/l of levothyroxine and 250 mg/l of methimazole in drinking water of rats, respectively, for 42 days. The white adipose tissues and serum sample were taken on days 15, 28, 42 and also 2 weeks after treatment cessation. Analysis of adiponectin gene expression was performed by real-time PCR and 2(-ΔΔct) method. The levels of adipose tissue adiponectin mRNA in the HYPO rats were decreased during the 6-week treatment when compared to control rats (adipose adiponectin gene expression was increased in HYPER rats during the 6-week treatment in parallel with an increase the thyroid hormones concentrations (P adipose tissue is regulated by thyroid hormones at the translation level and that lipid and carbohydrate disturbances in a patient with thyroid dysfunction may be, in part, due to adiponectin gene expression changes.

  17. Myocardial regeneration potential of adipose tissue-derived stem cells

    Energy Technology Data Exchange (ETDEWEB)

    Bai, Xiaowen, E-mail: baixw01@yahoo.com [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States); Alt, Eckhard, E-mail: ealt@mdanderson.org [Department of Molecular Pathology, The University of Texas M.D. Anderson Cancer Center, 1515 Holcombe, Houston, TX 77030 (United States)

    2010-10-22

    Research highlights: {yields} Various tissue resident stem cells are receiving tremendous attention from basic scientists and clinicians and hold great promise for myocardial regeneration. {yields} For practical reasons, human adipose tissue-derived stem cells are attractive stem cells for future clinical application in repairing damaged myocardium. {yields} This review summarizes the characteristics of cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential and the, underlying mechanisms, and safety issues. -- Abstract: Various tissue resident stem cells are receiving attention from basic scientists and clinicians as they hold promise for myocardial regeneration. For practical reasons, adipose tissue-derived stem cells (ASCs) are attractive cells for clinical application in repairing damaged myocardium based on the following advantages: abundant adipose tissue in most patients and easy accessibility with minimally invasive lipoaspiration procedure. Several recent studies have demonstrated that both cultured and freshly isolated ASCs could improve cardiac function in animal model of myocardial infarction. The mechanisms underlying the beneficial effect of ASCs on myocardial regeneration are not fully understood. Growing evidence indicates that transplantation of ASCs improve cardiac function via the differentiation into cardiomyocytes and vascular cells, and through paracrine pathways. Paracrine factors secreted by injected ASCs enhance angiogenesis, reduce cell apoptosis rates, and promote neuron sprouts in damaged myocardium. In addition, Injection of ASCs increases electrical stability of the injured heart. Furthermore, there are no reported cases of arrhythmia or tumorigenesis in any studies regarding myocardial regeneration with ASCs. This review summarizes the characteristics of both cultured and freshly isolated stem cells obtained from adipose tissue, their myocardial regeneration potential, and the

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

    Science.gov (United States)

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

    2015-08-01

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

  19. Hkat, a novel nutritionally regulated transmembrane protein in adipose tissues.

    Science.gov (United States)

    Zhang, Ren

    2012-01-01

    White adipose tissue is an active endocrine organ regulating many aspects of whole body physiology and pathology. Adipogenesis, a process in which premature cells differentiate into adipocytes, is a complex process that includes orchestrated changes in gene expression and cell morphology in response to various nutritional and hormonal stimuli. To profile transcriptome changes in response to nutritional stimulation, we performed RNA-seq on fat in mice treated with either a high-fat diet or fasting. We identified a novel nutritionally regulated gene, Gm12824, named Hkat (heart, kidney, adipose-enriched transmembrane protein). We show that both fasting and obesity dramatically reduce Hkat in white adipose tissue, and that fasting reduces while obesity increases its expression in brown fat. Hkat is localized to the plasma membrane and induced during adipogenesis. Therefore, Hkat is a novel nutritionally regulated gene that is potentially involved in metabolism.

  20. b-Series gangliosides crucially regulate leptin secretion in adipose tissues.

    Science.gov (United States)

    Ji, Shuting; Ohkawa, Yuki; Tokizane, Kyohei; Ohmi, Yuhsuke; Banno, Ryoichi; Furukawa, Keiko; Kiyama, Hiroshi; Furukawa, Koichi

    2015-04-01

    Gangliosides are widely involved in the regulation of cells and organs. However, little is known about their roles in leptin secretion from adipose tissues. Genetic deletion of b-series gangliosides resulted in the marked reduction of serum leptin. Expression analysis of leptin revealed that leptin accumulated in the adipose tissues of GD3 synthase-knockout (GD3S KO) mice. Analysis of primary cultured stromal vascular fractions (SVF) derived from GD3S KO mice revealed that leptin secretion was reduced, although leptin amounts in cells were increased compared with those of wild type. Interestingly, addition of b-series gangliosides to the culture medium of differentiated SVF resulted in the restoration of leptin secretion. Results of methyl-β-cyclodextrin treatment of differentiated 3T3-L1 cells as well as immunocytostaining of leptin and caveolin-1 suggested that b-series gangliosides regulate the leptin secretion from adipose tissues in lipid rafts.

  1. Differential effects of a gelatinase inhibitor on adipocyte differentiation and adipose tissue development.

    Science.gov (United States)

    Van Hul, Matthias; Bauters, Dries; Lijnen, Roger H

    2013-10-01

    (1) A potential role for the gelatinases in adipocyte differentiation in vitro and adipose tissue development in vivo was investigated using the gelatinase inhibitor tolylsam ((R)-3-methyl-2-[4-(3-p-tolyl-[1,2,4]oxadiazol-5-yl)-benzenesulphonylamino]-butyric acid). (2) Differentiation of murine 3T3-F442A preadipocytes (12 days after reaching confluence) into mature adipocytes in vitro was promoted in the presence of tolylsam (10-100 μmol/L). (3) De novo development of fat tissue in nude mice injected with preadipocytes and kept on a high-fat diet was significantly impaired following treatment with tolylsam (100 mg/kg per day for 4 weeks). (4) Adipose tissue development in matrix metalloproteinase (MMP)-2 deficient mice, kept on a high-fat diet, was significantly impaired following administration of tolylsam (100 mg/kg per day for 15 weeks). This was associated with markedly enhanced metabolic rate. (5) Treatment of MMP-2-deficient mice with tolylsam (100 mg/kg per day, 15 weeks) was associated with the preservation of collagen and a reduction in blood vessel size in adipose tissues in vivo. (6) Furthermore, plasma levels of triglycerides and free fatty acids were reduced by tolylsam treatment of MMP-2-deficient mice (100 mg/kg per day, 15 weeks), whereas nutrient adsorption in the intestine was not affected. (7) The results of the present study indicate that tolylsam promotes preadipocyte differentiation in vitro, but impairs adipose tissue development in vivo.

  2. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response. PMID:27148161

  3. Adipose tissue remodeling: its role in energy metabolism and metabolic disorders

    Directory of Open Access Journals (Sweden)

    Sung Sik eChoe

    2016-04-01

    Full Text Available The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue (WAT functions as a key energy reservoir for other organs, whereas the brown adipose tissue (BAT accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secret various hormones, cytokines, and metabolites (termed as adipokines that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic over-nutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  4. Adipose Tissue Remodeling: Its Role in Energy Metabolism and Metabolic Disorders.

    Science.gov (United States)

    Choe, Sung Sik; Huh, Jin Young; Hwang, In Jae; Kim, Jong In; Kim, Jae Bum

    2016-01-01

    The adipose tissue is a central metabolic organ in the regulation of whole-body energy homeostasis. The white adipose tissue functions as a key energy reservoir for other organs, whereas the brown adipose tissue accumulates lipids for cold-induced adaptive thermogenesis. Adipose tissues secrete various hormones, cytokines, and metabolites (termed as adipokines) that control systemic energy balance by regulating appetitive signals from the central nerve system as well as metabolic activity in peripheral tissues. In response to changes in the nutritional status, the adipose tissue undergoes dynamic remodeling, including quantitative and qualitative alterations in adipose tissue-resident cells. A growing body of evidence indicates that adipose tissue remodeling in obesity is closely associated with adipose tissue function. Changes in the number and size of the adipocytes affect the microenvironment of expanded fat tissues, accompanied by alterations in adipokine secretion, adipocyte death, local hypoxia, and fatty acid fluxes. Concurrently, stromal vascular cells in the adipose tissue, including immune cells, are involved in numerous adaptive processes, such as dead adipocyte clearance, adipogenesis, and angiogenesis, all of which are dysregulated in obese adipose tissue remodeling. Chronic overnutrition triggers uncontrolled inflammatory responses, leading to systemic low-grade inflammation and metabolic disorders, such as insulin resistance. This review will discuss current mechanistic understandings of adipose tissue remodeling processes in adaptive energy homeostasis and pathological remodeling of adipose tissue in connection with immune response.

  5. The Combination of Tissue Dissection and External Volume Expansion Generates Large Volumes of Adipose Tissue.

    Science.gov (United States)

    He, Yunfan; Dong, Ziqing; Xie, Gan; Zhou, Tao; Lu, Feng

    2017-04-01

    Noninvasive external volume expansion device has been applied to stimulate nonsurgical breast enlargement in clinical settings. Although previous results demonstrate the capacity of external volume expansion to increase the number of adipocytes, this strategy alone is insufficient to reconstruct soft-tissue defects or increase breast mass. The authors combined a minimally invasive tissue dissection method with external volume expansion to generate large volumes of adipose tissue. In vitro, various densities of adipose-derived stem cells were prepared to evaluate relations between cell contacts and cell proliferation. In vivo, dorsal adipose tissue of rabbits was thoroughly dissected and the external volume expansion device was applied to maintain the released state. External volume expansion without tissue dissection served as the control. In the dissection group, the generated adipose tissue volume was much larger than that in the control group at all time points. A larger number of proliferating cells appeared in the dissection samples than in the control samples at the early stage after tissue dissection. At low cell density, adipose-derived stem cells displayed an increasing proliferation rate compared to high cell density. Protein expression analysis revealed that cell proliferation was mediated by a similar mechanism both in vivo and in vitro, involving the release of cell contact inhibition and Hippo/Yes-associated protein pathway activation. Adipose tissue dissection releases cell-to-cell contacts and induces adipose-derived stem cell proliferation. Preexpanded adipose-derived stem cells undergo adipogenesis under the adipogenic environment created by external volume expansion, leading to better adipose regeneration compared with the control.

  6. Visceral adipose tissue area measurement at a single level: can it represent visceral adipose tissue volume?

    Science.gov (United States)

    Noumura, Yusuke; Kamishima, Tamotsu; Sutherland, Kenneth; Nishimura, Hideho

    2017-08-01

    Measurement of visceral adipose tissue (VAT) needs to be accurate and sensitive to change for risk monitoring. The purpose of this study is to determine the CT slice location where VAT area can best reflect changes in VAT volume and body weight. 60 plain abdominal CT images from 30 males [mean age (range) 51 (41-68) years, mean body weight (range) 71.1 (101.9-50.9) kg] who underwent workplace screenings twice within a 1-year interval were evaluated. Automatically calculated and manually corrected areas of the VAT of various scan levels using "freeform curve" region of interest on CT were recorded and compared with body weight changes. The strongest correlations of VAT area with VAT volume and body weight changes were shown in a slice 3 cm above the lower margin of L3 with r values of 0.853 and 0.902, respectively. VAT area measurement at a single level 3 cm above the lower margin of the L3 vertebra is feasible and can reflect changes in VAT volume and body weight. Advances in knowledge: As VAT area at a CT slice 3cm above the lower margin of L3 can best reflect interval changes in VAT volume and body weight, VAT area measurement should be selected at this location.

  7. Insulin receptor signaling in POMC, but Not AgRP, neurons controls adipose tissue insulin action

    National Research Council Canada - National Science Library

    Oberlin, Douglas; Chi, Tiffany; Buettner, Christoph; Shin, Andrew C; Degann, Seta; Filatova, Nika; Lindtner, Claudia

    2017-01-01

    Insulin is a key regulator of adipose tissue lipolysis, and impaired adipose tissue insulin action results in unrestrained lipolysis and lipotoxicity, which are hallmarks of the metabolic syndrome and diabetes...

  8. Subcutaneous abdominal adipose tissue lipolysis during exercise determined by arteriovenous measurements in older women

    DEFF Research Database (Denmark)

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

    2002-01-01

    To characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise.......To characterize the lipolytic response in the subcutaneous abdominal adipose tissue in older women to endurance exercise....

  9. Metabolic and Vascular Consequences of Adipose Tissue Dysfunction

    NARCIS (Netherlands)

    Westerink, J.|info:eu-repo/dai/nl/343038617

    2012-01-01

    Adipose Tissue Dysfunction (ATD) has been proposed as the pathophysiological route by which obesity confers its associated increased risk for cardiovascular disease and is characterized by an increased secretion of pro-inflammatory cytokines and adipokines and reduced secretion of anti-inflammatory

  10. Adipose Tissue Dysfunction : Clinical Relevance and Diagnostic Possibilities

    NARCIS (Netherlands)

    Schrover, I. M.; Spiering, W.; Leiner, T.; Visseren, F. L J

    2016-01-01

    Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity

  11. Endotrophin triggers adipose tissue fibrosis and metabolic dysfunction

    DEFF Research Database (Denmark)

    Sun, Kai; Park, Jiyoung; Gupta, Olga T

    2014-01-01

    We recently identified endotrophin as an adipokine with potent tumour-promoting effects. However, the direct effects of local accumulation of endotrophin in adipose tissue have not yet been studied. Here we use a doxycycline-inducible adipocyte-specific endotrophin overexpression model to demonst...

  12. Adipose Tissue Dysfunction : Clinical Relevance and Diagnostic Possibilities

    NARCIS (Netherlands)

    Schrover, I. M.; Spiering, W.; Leiner, T.; Visseren, F. L J

    2016-01-01

    Adipose tissue dysfunction is defined as an imbalance between pro- and anti-inflammatory adipokines, causing insulin resistance, systemic low-grade inflammation, hypercoagulability, and elevated blood pressure. These can lead to cardiovascular disease and diabetes mellitus type 2. Although quantity

  13. Obesity induces a phenotypic switch in adipose tissue macrophage polarization.

    Science.gov (United States)

    Lumeng, Carey N; Bodzin, Jennifer L; Saltiel, Alan R

    2007-01-01

    Adipose tissue macrophages (ATMs) infiltrate adipose tissue during obesity and contribute to insulin resistance. We hypothesized that macrophages migrating to adipose tissue upon high-fat feeding may differ from those that reside there under normal diet conditions. To this end, we found a novel F4/80(+)CD11c(+) population of ATMs in adipose tissue of obese mice that was not seen in lean mice. ATMs from lean mice expressed many genes characteristic of M2 or "alternatively activated" macrophages, including Ym1, arginase 1, and Il10. Diet-induced obesity decreased expression of these genes in ATMs while increasing expression of genes such as those encoding TNF-alpha and iNOS that are characteristic of M1 or "classically activated" macrophages. Interestingly, ATMs from obese C-C motif chemokine receptor 2-KO (Ccr2-KO) mice express M2 markers at levels similar to those from lean mice. The antiinflammatory cytokine IL-10, which was overexpressed in ATMs from lean mice, protected adipocytes from TNF-alpha-induced insulin resistance. Thus, diet-induced obesity leads to a shift in the activation state of ATMs from an M2-polarized state in lean animals that may protect adipocytes from inflammation to an M1 proinflammatory state that contributes to insulin resistance.

  14. Spice Up Your Life: Adipose Tissue and Inflammation

    Directory of Open Access Journals (Sweden)

    Anil K. Agarwal

    2014-01-01

    Full Text Available Cells of the immune system are now recognized in the adipose tissue which, in obesity, produces proinflammatory chemokines and cytokines. Several herbs and spices have been in use since ancient times which possess anti-inflammatory properties. In this perspective, I discuss and propose the usage of these culinary delights for the benefit of human health.

  15. Endocrine modulators of mouse subcutaneous adipose tissue beige adipocyte markers

    Science.gov (United States)

    The stromal vascular fraction (SVF) of subcutaneous adipose tissue contains precursors that can give rise to beige adipocytes. Beige adipocytes are characterized by the expression of specific markers, but it is not clear which markers best evaluate beige adipocyte differentiation. Both regulators of...

  16. Browning attenuates murine white adipose tissue expansion during postnatal development.

    Science.gov (United States)

    Lasar, D; Julius, A; Fromme, T; Klingenspor, M

    2013-05-01

    During postnatal development of mice distinct white adipose tissue depots display a transient appearance of brown-like adipocytes. These brite (brown in white) adipocytes share characteristics with classical brown adipocytes including a multilocular appearance and the expression of the thermogenic protein uncoupling protein 1. In this study, we compared two inbred mouse strains 129S6sv/ev and C57BL6/N known for their different propensity to diet-induced obesity. We observed transient browning in retroperitoneal and inguinal adipose tissue depots of these two strains. From postnatal day 10 to 20 the increase in the abundance of multilocular adipocytes and uncoupling protein 1 expression was higher in 129S6sv/ev than in C57BL6/N pups. The parallel increase in the mass of the two fat depots was attenuated during this browning period. Conversely, epididymal white and interscapular brown adipose tissue displayed a steady increase in mass during the first 30 days of life. In this period, 129S6sv/ev mice developed a significantly higher total body fat mass than C57BL6/N. Thus, while on a local depot level a high number of brite cells is associated with the attenuation of adipose tissue expansion the strain comparison reveals no support for a systemic impact on energy balance. This article is part of a Special Issue entitled Brown and White Fat: From Signaling to Disease.

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

    NARCIS (Netherlands)

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

    2015-01-01

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

  18. Healing of grafted adipose tissue: current clinical applications of adipose-derived stem cells for breast and face reconstruction.

    Science.gov (United States)

    Philips, Brian J; Marra, Kacey G; Rubin, J Peter

    2014-05-01

    Since their isolation and characterization nearly a decade ago, adipose-derived stem cells (ASCs) have become one of the most popular adult stem cell populations for soft tissue engineering and regenerative medicine applications. Compared with other stem cell sources, ASCs offer several advantages including abundant autologous source, minor invasive harvesting (liposuction), significant proliferative capacity in culture, and multilineage potential. In this mini review, we focus on some of the more salient published clinical and preclinical data to date regarding ASC treatment for breast and facial soft tissue reconstruction. © 2014 by the Wound Healing Society.

  19. Endoplasmic reticulum stress is increased in adipose tissue of women with gestational diabetes.

    Directory of Open Access Journals (Sweden)

    Stella Liong

    Full Text Available Maternal obesity and gestational diabetes mellitus (GDM are two increasingly common and important obstetric complications that are associated with severe long-term health risks to mothers and babies. IL-1β, which is increased in obese and GDM pregnancies, plays an important role in the pathophysiology of these two pregnancy complications. In non-pregnant tissues, endoplasmic (ER stress is increased in diabetes and can induce IL-1β via inflammasome activation. The aim of this study was to determine whether ER stress is increased in omental adipose tissue of women with GDM, and if ER stress can also upregulate inflammasome-dependent secretion of IL-1β. ER stress markers IRE1α, GRP78 and XBP-1s were significantly increased in adipose tissue of obese compared to lean pregnant women. ER stress was also increased in adipose tissue of women with GDM compared to BMI-matched normal glucose tolerant (NGT women. Thapsigargin, an ER stress activator, induced upregulated secretion of mature IL-1α and IL-1β in human omental adipose tissue explants primed with bacterial endotoxin LPS, the viral dsRNA analogue poly(I:C or the pro-inflammatory cytokine TNF-α. Inhibition of capase-1 with Ac-YVAD-CHO resulted in decreased IL-1α and IL-1β secretion, whereas inhibition of pannexin-1 with carbenoxolone suppressed IL-1β secretion only. Treatment with anti-diabetic drugs metformin and glibenclamide also reduced IL-1α and IL-1β secretion in infection and cytokine-primed adipose tissue. In conclusion, this study has demonstrated ER stress to activate the inflammasome in pregnant adipose tissue. Therefore, increased ER stress may contribute towards the pathophysiology of obesity in pregnancy and GDM.

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

    Science.gov (United States)

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

    1998-02-01

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

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

    Directory of Open Access Journals (Sweden)

    Liming Liu

    2017-01-01

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

  2. Adipose tissue-specific dysregulation of angiotensinogen by oxidative stress in obesity

    OpenAIRE

    2010-01-01

    Adipose tissue expresses all components of the renin-angiotensin system including angiotensinogen (AGT). Recent studies have highlighted a potential role of AGT in adipose tissue function and homeostasis. However, some controversies surround the regulatory mechanisms of AGT in obese adipose tissue. In this context, we here demonstrated that the AGT messenger RNA (mRNA) level in human subcutaneous adipose tissue was significantly reduced in obese subjects as compared with nonobese subjects. Ad...

  3. Thematic review series: Adipocyte Biology. Adipose tissue function and plasticity orchestrate nutritional adaptation

    OpenAIRE

    Sethi, Jaswinder K.; Vidal-Puig, Antonio J

    2007-01-01

    This review focuses on adipose tissue biology and introduces the concept of adipose tissue plasticity and expandability as key determinants of obesity-associated metabolic dysregulation. This concept is fundamental to our understanding of adipose tissue as a dynamic organ at the center of nutritional adaptation. Here, we summarize the current knowledge of the mechanisms by which adipose tissue can affect peripheral energy homeostasis, particularly in the context of overnutrition. Two mechanis...

  4. A Story in Brown and White Regulation of Metabolic Homeostasis by Brown Adipose tissue

    OpenAIRE

    Mössenböck, Karin

    2016-01-01

    Adipose tissue exists in three shades: White adipose tissue (WAT), the site of energy storage, brown adipose tissue (BAT), which burns nutrients to generate heat and maintain body temperature, and brown in white adipose tissue (brite AT), which represents WAT adapting BAT features in cold exposure. Thermogenically active BAT has been discovered in adult humans and inversely correlates with obesity and insulin resistance. The link between impaired insulin sensitivity and the browning of adipos...

  5. Adipose Tissue Branched Chain Amino Acid (BCAA) Metabolism Modulates Circulating BCAA Levels*

    OpenAIRE

    Herman, Mark A.; She, Pengxiang; Peroni, Odile D.; Lynch, Christopher J.; Kahn, Barbara B.

    2010-01-01

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent obse...

  6. Caspase Induction and BCL2 Inhibition in Human Adipose Tissue

    Science.gov (United States)

    Tinahones, Francisco José; Coín Aragüez, Leticia; Murri, Mora; Oliva Olivera, Wilfredo; Mayas Torres, María Dolores; Barbarroja, Nuria; Gomez Huelgas, Ricardo; Malagón, Maria M.; El Bekay, Rajaa

    2013-01-01

    OBJECTIVE Cell death determines the onset of obesity and associated insulin resistance. Here, we analyze the relationship among obesity, adipose tissue apoptosis, and insulin signaling. RESEARCH DESIGN AND METHODS The expression levels of initiator (CASP8/9) and effector (CASP3/7) caspases as well as antiapoptotic B-cell lymphoma (BCL)2 and inflammatory markers were assessed in visceral (VAT) and subcutaneous (SAT) adipose tissue from patients with different degrees of obesity and without insulin resistance or diabetes. Adipose tissue explants from lean subjects were cultured with TNF-α or IL-6, and the expression of apoptotic and insulin signaling components was analyzed and compared with basal expression levels in morbidly obese subjects. RESULTS SAT and VAT exhibited increased CASP3/7 and CASP8/9 expression levels and decreased BCL2 expression with BMI increase. These changes were accompanied by increased inflammatory cytokine mRNA levels and macrophage infiltration markers. In obese subjects, CASP3/7 activation and BCL2 downregulation correlated with the IRS-1/2–expression levels. Expression levels of caspases, BCL2, p21, p53, IRS-1/2, GLUT4, protein tyrosine phosphatase 1B, and leukocyte antigen-related phosphatase in TNF-α– or IL-6–treated explants from lean subjects were comparable with those found in adipose tissue samples from morbidly obese subjects. These insulin component expression levels were reverted with CASP3/7 inhibition in these TNF-α– or IL-6–treated explants. CONCLUSIONS Body fat mass increase is associated with CASP3/7 and BCL2 expression in adipose tissue. Moreover, this proapoptotic state correlated with insulin signaling, suggesting its potential contribution to the development of insulin resistance. PMID:23193206

  7. Allergen exposure induces adipose tissue inflammation and insulin resistance.

    Science.gov (United States)

    Jung, Chien-Cheng; Tsai, Yau-Sheng; Chang, Chih-Ching; Cheng, Tsun-Jen; Chang, Ching-Wen; Liu, Ping-Yen; Chiu, Yi-Jen; Su, Huey-Jen

    2014-11-01

    This study investigates whether exposure to allergen elicits insulin resistance as a result of adipose tissue inflammation. Male C57BL/6 mice were challenged with ovalbumin (OVA) allergen for 12 weeks, and blood and adipose tissue samples were collected at 24h after the last challenge. Levels of adhesion molecules, fasting insulin, fasting glucose, and adipokines in the blood were analyzed, and fasting homeostasis model assessment was applied to determine insulin resistance (HOMA-IR). The expression of pro- and anti-inflammatory genes in dissected adipose tissues was analyzed by real-time RT-PCR. Our results showed that OVA exposure increased insulin resistance as well as resistin and E-selectin, but reduced adiponectin in the serum. Resistin level was significantly correlated with HOMA-IR. Moreover, in adipose tissues of OVA-challenged mice, the pro-inflammatory M1 genes were more abundant while the anti-inflammatory M2 genes were less than those of PBS-treated mice. The expressional changes of both M1 and M2 genes were significantly associated with serum levels of adiponectin, resistin, and E-selectin. Hematoxylin and eosin (HE) and immunohistochemistry (IHC) stain also showed that there was more obvious inflammation in OVA-challenged mice. In conclusion, the current study suggests the relationship between allergen-elicited adipose tissue inflammation and circulating inflammatory molecules, which are possible mediators for the development of insulin resistance. Therefore, we propose that allergen exposure might be one risk factor for insulin resistance. Copyright © 2014 Elsevier B.V. All rights reserved.

  8. Exercise Effects on White Adipose Tissue: Beiging and Metabolic Adaptations.

    Science.gov (United States)

    Stanford, Kristin I; Middelbeek, Roeland J W; Goodyear, Laurie J

    2015-07-01

    Regular physical activity and exercise training have long been known to cause adaptations to white adipose tissue (WAT), including decreases in cell size and lipid content and increases in mitochondrial proteins. In this article, we discuss recent studies that have investigated the effects of exercise training on mitochondrial function, the "beiging" of WAT, regulation of adipokines, metabolic effects of trained adipose tissue on systemic metabolism, and depot-specific responses to exercise training. The major WAT depots in the body are found in the visceral cavity (vWAT) and subcutaneously (scWAT). In rodent models, exercise training increases mitochondrial biogenesis and activity in both these adipose tissue depots. Exercise training also increases expression of the brown adipocyte marker uncoupling protein 1 (UCP1) in both adipose tissue depots, although these effects are much more pronounced in scWAT. Consistent with the increase in UCP1, exercise training increases the presence of brown-like adipocytes in scWAT, also known as browning or beiging. Training results in changes in the gene expression of thousands of scWAT genes and an altered adipokine profile in both scWAT and vWAT. Transplantation of trained scWAT in sedentary recipient mice results in striking improvements in skeletal muscle glucose uptake and whole-body metabolic homeostasis. Human and rodent exercise studies have indicated that exercise training can alter circulating adipokine concentration as well as adipokine expression in adipose tissue. Thus, the profound changes to WAT in response to exercise training may be part of the mechanism by which exercise improves whole-body metabolic health.

  9. Alteration of local adipose tissue trace element homeostasis as a possible mechanism of obesity-related insulin resistance.

    Science.gov (United States)

    Tinkov, Alexey A; Sinitskii, Anton I; Popova, Elizaveta V; Nemereshina, Olga N; Gatiatulina, Evgenia R; Skalnaya, Margarita G; Skalny, Anatoly V; Nikonorov, Alexandr A

    2015-09-01

    The mechanisms of association between obesity and the related metabolic disturbances in general and insulin resistance in particular are extensively studied. Taking into account a key role of adipose tissue insulin resistance in the development of systemic obesity-related insulin resistance, the estimation of mechanisms linking increased adiposity and impaired insulin signaling in adipocytes will allow to develop novel prophylactic and therapeutic approaches to treatment of these states. A number of trace elements like chromium, zinc, and vanadium have been shown to take part in insulin signaling via various mechanisms. Taking into account a key role of adipocyte in systemic carbohydrate homeostasis it can be asked if trace element homeostasis in adipose tissue may influence regulatory mechanisms of glucose metabolism. We hypothesize that caloric excess through currently unknown mechanisms results in decreased chromium, vanadium, and zinc content in adipocytes. Decreased content of trace elements in the adipose tissue causes impairment of intra-adipocyte insulin signaling subsequently leading to adipose tissue insulin resistance. The latter significantly contributes to systemic insulin resistance and further metabolic disruption in obesity. It is also possible that decreased adipose tissue trace element content is associated with dysregulation of insulin-sensitizing and proinflammatory adipokines also leading to insulin resistance. We hypothesize that insulin resistance and adipokine dysbalance increase the severity of obesity subsequently aggravating alteration of adipose tissue trace element balance. Single indications of high relative adipose tissue trace element content, decreased Cr, V, and Zn content in obese adipose tissue, and tight association between fat tissue chromium, vanadium, and zinc levels and metabolic parameters in obesity may be useful for hypothesis validation. If our hypothesis will be confirmed by later studies, adipose tissue chromium

  10. Beyond fat grafting: what adipose tissue can teach us about the molecular mechanisms of human aging.

    Science.gov (United States)

    Stransky, Carrie A; Hsu, Vivian M; Dierov, Raia; Hoover, William J; Donahue, Greg; Bucky, Louis P; Percec, Ivona

    2012-10-01

    molecular mechanisms of human aging. Our findings are consistent with the hypothesis that epigenetic modifications play a more important role than transcriptional modifications in early human adipose tissue aging. Our future studies will examine the contribution of specific epigenetic markers to human adipose tissue aging and promise to advance approaches in regenerative medicine, and the prevention and treatment of aging.

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

    NARCIS (Netherlands)

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

    2016-01-01

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

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  2. Adipose tissue and metabolic syndrome: too much, too little or neither.

    Science.gov (United States)

    Grundy, Scott M

    2015-11-01

    Obesity is strongly associated with metabolic syndrome. Recent research suggests that excess adipose tissue plays an important role in development of the syndrome. On the other hand, persons with a deficiency of adipose tissue (e.g. lipodystrophy) also manifest the metabolic syndrome. In some animal models, expansion of adipose tissue pools mitigates adverse metabolic components (e.g. insulin resistance, hyperglycaemia and dyslipidemia). Hence, there are conflicting data as to whether adipose tissue worsens the metabolic syndrome or protects against it. This conflict may relate partly to locations of adipose tissue pools. For instance, lower body adipose tissue may be protective whereas upper body adipose tissue may promote the syndrome. One view holds that in either case, the accumulation of ectopic fat in muscle and liver is the driving factor underlying the syndrome. If so, there may be some link between adipose tissue fat and ectopic fat. But the mechanisms underlying this connection are not clear. A stronger association appears to exist between excessive caloric intake and ectopic fat accumulation. Adipose tissue may act as a buffer to reduce the impact of excess energy consumption by fat storage; but once a constant weight has been achieved, it is unclear whether adipose tissue influences levels of ectopic fat. Another mechanism whereby adipose tissue could worsen the metabolic syndrome is through release of adipokines. This is an intriguing mechanism, but the impact of adipokines on metabolic syndrome risk factors is uncertain. Thus, many potential connections between adipose tissue and metabolic syndrome remain to unravelled.

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  5. Interleukin-17A Differentially Induces Inflammatory and Metabolic Gene Expression in the Adipose Tissues of Lean and Obese Mice.

    Science.gov (United States)

    Qu, Yine; Zhang, Qiuyang; Ma, Siqi; Liu, Sen; Chen, Zhiquan; Mo, Zhongfu; You, Zongbing

    2016-04-07

    The functions of interleukin-17A (IL-17A) in adipose tissues and adipocytes have not been well understood. In the present study, male mice were fed with a regular diet (n = 6, lean mice) or a high-fat diet (n = 6, obese mice) for 30 weeks. Subcutaneous adipose tissue (SAT) and visceral adipose tissue (VAT) were analyzed for IL-17A levels. SAT and VAT were treated with IL-17A and analyzed for inflammatory and metabolic gene expression. Mouse 3T3-L1 pre-adipocytes were differentiated into adipocytes, followed with IL-17A treatment and analysis for inflammatory and metabolic gene expression. We found that IL-17A levels were higher in obese SAT than lean SAT; the basal expression of inflammatory and metabolic genes was different between SAT and VAT and between lean and obese adipose tissues. IL-17A differentially induced expression of inflammatory and metabolic genes, such as tumor necrosis factor α, Il-6, Il-1β, leptin, and glucose transporter 4, in adipose tissues of lean and obese mice. IL-17A also differentially induced expression of inflammatory and metabolic genes in pre-adipocytes and adipocytes, and IL-17A selectively activated signaling pathways in adipose tissues and adipocytes. These findings suggest that IL-17A differentially induces inflammatory and metabolic gene expression in the adipose tissues of lean and obese mice.

  6. Interleukin-17A Differentially Induces Inflammatory and Metabolic Gene Expression in the Adipose Tissues of Lean and Obese Mice

    Directory of Open Access Journals (Sweden)

    Yine Qu

    2016-04-01

    Full Text Available The functions of interleukin-17A (IL-17A in adipose tissues and adipocytes have not been well understood. In the present study, male mice were fed with a regular diet (n = 6, lean mice or a high-fat diet (n = 6, obese mice for 30 weeks. Subcutaneous adipose tissue (SAT and visceral adipose tissue (VAT were analyzed for IL-17A levels. SAT and VAT were treated with IL-17A and analyzed for inflammatory and metabolic gene expression. Mouse 3T3-L1 pre-adipocytes were differentiated into adipocytes, followed with IL-17A treatment and analysis for inflammatory and metabolic gene expression. We found that IL-17A levels were higher in obese SAT than lean SAT; the basal expression of inflammatory and metabolic genes was different between SAT and VAT and between lean and obese adipose tissues. IL-17A differentially induced expression of inflammatory and metabolic genes, such as tumor necrosis factor α, Il-6, Il-1β, leptin, and glucose transporter 4, in adipose tissues of lean and obese mice. IL-17A also differentially induced expression of inflammatory and metabolic genes in pre-adipocytes and adipocytes, and IL-17A selectively activated signaling pathways in adipose tissues and adipocytes. These findings suggest that IL-17A differentially induces inflammatory and metabolic gene expression in the adipose tissues of lean and obese mice.

  7. Circadian regulation of lipid mobilization in white adipose tissues.

    Science.gov (United States)

    Shostak, Anton; Meyer-Kovac, Judit; Oster, Henrik

    2013-07-01

    In mammals, a network of circadian clocks regulates 24-h rhythms of behavior and physiology. Circadian disruption promotes obesity and the development of obesity-associated disorders, but it remains unclear to which extent peripheral tissue clocks contribute to this effect. To reveal the impact of the circadian timing system on lipid metabolism, blood and adipose tissue samples from wild-type, ClockΔ19, and Bmal1(-/-) circadian mutant mice were subjected to biochemical assays and gene expression profiling. We show diurnal variations in lipolysis rates and release of free fatty acids (FFAs) and glycerol into the blood correlating with rhythmic regulation of two genes encoding the lipolysis pacemaker enzymes, adipose triglyceride (TG) lipase and hormone-sensitive lipase, by self-sustained adipocyte clocks. Circadian clock mutant mice show low and nonrhythmic FFA and glycerol blood content together with decreased lipolysis rates and increased sensitivity to fasting. Instead circadian clock disruption promotes the accumulation of TGs in white adipose tissue (WAT), leading to increased adiposity and adipocyte hypertrophy. In summary, circadian modulation of lipolysis rates regulates the availability of lipid-derived energy during the day, suggesting a role for WAT clocks in the regulation of energy homeostasis.

  8. Epicardial Adipose Tissue Thickness in Patients With Subclinical Hypothyroidism and the Relationship Thereof With Visceral Adipose Tissue Thickness.

    Science.gov (United States)

    Arpaci, Dilek; Gurkan Tocoglu, Aysel; Yilmaz, Sabiye; Korkmaz, Sumeyye; Ergenc, Hasan; Gunduz, Huseyin; Keser, Nurgul; Tamer, Ali

    2016-03-01

    Subclinical hypothyroidism (SH) is associated with cardiovascular metabolic syndromes, especially dislipidemia and abdominal obesity. Visceral abdominal adipose tissue (VAAT) and epicardial adipose tissue (EAT) have the same ontogenic origin and produce many proinflammatory and proatherogenic cytokines. We evaluated EAT and VAAT thickness in patients with SH. Forty-one patients with SH and 35 controls were included in the study. Demographical and anthropometric features of both patients and controls were recorded. Thyroid and metabolic parameters were measured. EAT was measured using 2D-transthoracic echocardiography. The age and gender distributions were similar in the two groups (P = 0.998 and P = 0.121, respectively). Body mass index (BMI), fat mass, waist circumference (WC), hip circumference (HC), the WC/HC ratio, and the thicknesses of VAAT and abdominal subcutaneous adipose tissue were higher in the case group than the control group (all P values 0.05). We found no difference between the two groups in fasting plasma glucose (FPG) level (P = 0.780), but the levels of LDL-C and TG differed significantly (P = 0.002 and P = 0.026, respectively). The serum TSH level was higher and the FT4 level was lower in the case than the control group (both P values <0.01). Increased abdominal adipose tissue thickness in patients with SH is associated with atherosclerosis. To detemine the risk of atherosclerosis in such patients, EAT measurements are valuable; such assessment is simple to perform.

  9. Photoinduced cell morphology alterations quantified within adipose tissues by spectral optical coherence tomography.

    Science.gov (United States)

    Yanina, Irina Yu; Trunina, Natalia A; Tuchin, Valery V

    2013-11-01

    Morphological changes of the adipose tissue at phototreatment are studied in vitro using optical coherence tomography. The 200 to 600 μm fat tissue slices are used in the experiments. The observed change in the tissue structure was associated with fat cell lipolysis and destruction caused by the photodynamic effect. It is found that overall heating of a sample from room to physiological temperature leads to deeper and faster morphology tissue changes if other processing conditions are kept constant. These data support the hypothesis that photodynamic/photothermal treatment induces fat cell lipolysis during some period after treatment.

  10. Regulation of visceral adipose tissue-derived serine protease inhibitor by nutritional status, metformin, gender and pituitary factors in rat white adipose tissue.

    Science.gov (United States)

    González, C R; Caminos, J E; Vázquez, M J; Garcés, M F; Cepeda, L A; Angel, A; González, A C; García-Rendueles, M E; Sangiao-Alvarellos, S; López, M; Bravo, S B; Nogueiras, R; Diéguez, C

    2009-07-15

    Visceral adipose tissue-derived serine protease inhibitor (vaspin) is a recently discovered adipocytokine mainly secreted from visceral adipose tissue, which plays a main role in insulin sensitivity. In this study, we have investigated the regulation of vaspin gene expression in rat white adipose tissue (WAT) in different physiological (nutritional status, pregnancy, age and gender) and pathophysiological (gonadectomy, thyroid status and growth hormone deficiency) settings known to be associated with energy homeostasis and alterations in insulin sensitivity. We have determined vaspin gene expression by real-time PCR. Vaspin was decreased after fasting and its levels were partially recovered after leptin treatment. Chronic treatment with metformin increased vaspin gene expression. Vaspin mRNA expression reached the highest peak at 45 days in both sexes after birth and its expression was higher in females than males, but its levels did not change throughout pregnancy. Finally, decreased levels of growth hormone and thyroid hormones suppressed vaspin expression. These findings suggest that WAT vaspin mRNA expression is regulated by nutritional status, and leptin seems to be the nutrient signal responsible for those changes. Vaspin is influenced by age and gender, and its expression is increased after treatment with insulin sensitizers. Finally, alterations in pituitary functions modify vaspin levels. Understanding the molecular mechanisms regulating vaspin will provide new insights into the pathogenesis of the metabolic syndrome.

  11. Heterogeneous response of adipose tissue to cancer cachexia

    Directory of Open Access Journals (Sweden)

    P.S. Bertevello

    2001-09-01

    Full Text Available Cancer cachexia causes disruption of lipid metabolism. Since it has been well established that the various adipose tissue depots demonstrate different responses to stimuli, we assessed the effect of cachexia on some biochemical and morphological parameters of adipocytes obtained from the mesenteric (MES, retroperitoneal (RPAT, and epididymal (EAT adipose tissues of rats bearing Walker 256 carcinosarcoma, compared with controls. Relative weight and total fat content of tissues did not differ between tumor-bearing rats and controls, but fatty acid composition was modified by cachexia. Adipocyte dimensions were increased in MES and RPAT from tumor-bearing rats, but not in EAT, in relation to control. Ultrastructural alterations were observed in the adipocytes of tumor-bearing rat RPAT (membrane projections and EAT (nuclear bodies.

  12. The role of estrogen in adipose tissue metabolism: insights into glucose homeostasis regulation.

    Science.gov (United States)

    Kim, Jun Ho; Cho, Hyung Taek; Kim, Young Jun

    2014-01-01

    Adipose tissue is an organ with active endocrine function involved in the regulation of energy balance and glucose homeostasis via multiple metabolic signaling pathways targeting the brain, liver, skeletal muscle, pancreas, and other organs. There is increasing evidence demonstrating that the female sex hormone, estrogen, regulates adipose development and improves systemic glucose homeostasis in both males and females. The underlying mechanism linking estrogenic regulation in adipose tissue and systemic glucose metabolism has not been fully elucidated, but is thought to include interactions of estrogen receptor signaling events involving lipolytic and/or lipogenic enzyme activity, free fatty acid metabolism, and adipocytokine production. Thus, understanding the effects of estrogen replacement on adipose tissue biology and metabolism is important in determining the risk of developing obesity-related metabolic disorders in patients undergoing treatment for sex hormone deficiency. In this report, we review literature regarding the role of estrogens and their corresponding receptors in the control of adipose metabolism and glucose homeostasis in both rodents and humans. We also discuss the effects of selective estrogen receptor modulators on glucose metabolism.

  13. Adipose tissue branched chain amino acid (BCAA) metabolism modulates circulating BCAA levels.

    Science.gov (United States)

    Herman, Mark A; She, Pengxiang; Peroni, Odile D; Lynch, Christopher J; Kahn, Barbara B

    2010-04-09

    Whereas the role of adipose tissue in glucose and lipid homeostasis is widely recognized, its role in systemic protein and amino acid metabolism is less well-appreciated. In vitro and ex vivo experiments suggest that adipose tissue can metabolize substantial amounts of branched chain amino acids (BCAAs). However, the role of adipose tissue in regulating BCAA metabolism in vivo is controversial. Interest in the contribution of adipose tissue to BCAA metabolism has been renewed with recent observations demonstrating down-regulation of BCAA oxidation enzymes in adipose tissue in obese and insulin-resistant humans. Using gene set enrichment analysis, we observe alterations in adipose-tissue BCAA enzyme expression caused by adipose-selective genetic alterations in the GLUT4 glucose-transporter expression. We show that the rate of adipose tissue BCAA oxidation per mg of tissue from normal mice is higher than in skeletal muscle. In mice overexpressing GLUT4 specifically in adipose tissue, we observe coordinate down-regulation of BCAA metabolizing enzymes selectively in adipose tissue. This decreases BCAA oxidation rates in adipose tissue, but not in muscle, in association with increased circulating BCAA levels. To confirm the capacity of adipose tissue to modulate circulating BCAA levels in vivo, we demonstrate that transplantation of normal adipose tissue into mice that are globally defective in peripheral BCAA metabolism reduces circulating BCAA levels by 30% (fasting)-50% (fed state). These results demonstrate for the first time the capacity of adipose tissue to catabolize circulating BCAAs in vivo and that coordinate regulation of adipose-tissue BCAA enzymes may modulate circulating BCAA levels.

  14. Modulation of age-related insulin sensitivity by VEGF-dependent vascular plasticity in adipose tissues.

    Science.gov (United States)

    Honek, Jennifer; Seki, Takahiro; Iwamoto, Hideki; Fischer, Carina; Li, Jingrong; Lim, Sharon; Samani, Nilesh J; Zang, Jingwu; Cao, Yihai

    2014-10-14

    Mechanisms underlying age-related obesity and insulin resistance are generally unknown. Here, we report age-related adipose vascular changes markedly modulated fat mass, adipocyte functions, blood lipid composition, and insulin sensitivity. Notably, VEGF expression levels in various white adipose tissues (WATs) underwent changes uninterruptedly in different age populations. Anti-VEGF and anti- VEGF receptor 2 treatment in different age populations showed marked variations of vascular regression, with midaged mice exhibiting modest sensitivity. Interestingly, anti-VEGF treatment produced opposing effects on WAT adipocyte sizes in different age populations and affected vascular density and adipocyte sizes in brown adipose tissue. Consistent with changes of vasculatures and adipocyte sizes, anti-VEGF treatment increased insulin sensitivity in young and old mice but had no effects in the midaged group. Surprisingly, anti-VEGF treatment significantly improved insulin sensitivity in midaged obese mice fed a high-fat diet. Our findings demonstrate that adipose vasculatures show differential responses to anti-VEGF treatment in various age populations and have therapeutic implications for treatment of obesity and diabetes with anti-VEGF-based antiangiogenic drugs.

  15. Treatment of rats with a self-selected hyperlipidic diet, increases the lipid content of the main adipose tissue sites in a proportion similar to that of the lipids in the rest of organs and tissues.

    Science.gov (United States)

    Romero, María Del Mar; Roy, Stéphanie; Pouillot, Karl; Feito, Marisol; Esteve, Montserrat; Grasa, María Del Mar; Fernández-López, José-Antonio; Alemany, Marià; Remesar, Xavier

    2014-01-01

    Adipose tissue (AT) is distributed as large differentiated masses, and smaller depots covering vessels, and organs, as well as interspersed within them. The differences between types and size of cells makes AT one of the most disperse and complex organs. Lipid storage is partly shared by other tissues such as muscle and liver. We intended to obtain an approximate estimation of the size of lipid reserves stored outside the main fat depots. Both male and female rats were made overweight by 4-weeks feeding of a cafeteria diet. Total lipid content was analyzed in brain, liver, gastrocnemius muscle, four white AT sites: subcutaneous, perigonadal, retroperitoneal and mesenteric, two brown AT sites (interscapular and perirenal) and in a pool of the rest of organs and tissues (after discarding gut contents). Organ lipid content was estimated and tabulated for each individual rat. Food intake was measured daily. There was a surprisingly high proportion of lipid not accounted for by the main macroscopic AT sites, even when brain, liver and BAT main sites were discounted. Muscle contained about 8% of body lipids, liver 1-1.4%, four white AT sites lipid 28-63% of body lipid, and the rest of the body (including muscle) 38-44%. There was a good correlation between AT lipid and body lipid, but lipid in "other organs" was highly correlated too with body lipid. Brain lipid was not. Irrespective of dietary intake, accumulation of body fat was uniform both for the main lipid storage and handling organs: large masses of AT (but also liver, muscle), as well as in the "rest" of tissues. These storage sites, in specialized (adipose) or not-specialized (liver, muscle) tissues reacted in parallel against a hyperlipidic diet challenge. We postulate that body lipid stores are handled and regulated coordinately, with a more centralized and overall mechanisms than usually assumed.

  16. Fetal development of subcutaneous white adipose tissue is dependent on Zfp423

    Directory of Open Access Journals (Sweden)

    Mengle Shao

    2017-01-01

    Conclusions: Our results reveal that Zfp423 is essential for the terminal differentiation of subcutaneous white adipocytes during fetal adipose tissue development. Moreover, our data highlight the striking adverse effects of pathological subcutaneous adipose tissue remodeling on visceral adipose function and systemic nutrient homeostasis in obesity. Importantly, these data reveal the distinct phenotypes that can occur when adiponectin driven transgenes are activated in fetal vs. adult adipose tissue.

  17. Adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL) deficiencies affect expression of lipolytic activities in mouse adipose tissues.

    Science.gov (United States)

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

    2012-12-01

    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 patterns of brown and white adipose tissue from ATGL (-/-) and HSL (-/-) mice using differential activity-based gel electrophoresis. This method is based on activity-recognition probes possessing the same substrate analogous structure but carrying different fluorophores for specific detection of the enzyme patterns of two different tissues in one electrophoresis gel. We found that ATGL-deficiency in brown adipose tissue had a profound effect on the expression levels of other lipolytic and esterolytic enzymes in this tissue, whereas HSL-deficiency hardly showed any effect in brown adipose tissue. Neither ATGL- nor HSL-deficiency greatly influenced the lipase patterns in white adipose tissue. Enzyme activities of mouse tissues on acylglycerol substrates were analyzed as well, showing that ATGL-and HSL-deficiencies can be compensated for at least in part by other enzymes. The proteins that responded to ATGL-deficiency in brown adipose tissue were overexpressed and their activities on acylglycerols were analyzed. Among these enzymes, Es1, Es10, and Es31-like represent lipase candidates as they catalyze the hydrolysis of long-chain acylglycerols.

  18. Adipose tissue biglycan as a potential anti-inflammatory target of sodium salicylate in mice fed a high fat diet

    Directory of Open Access Journals (Sweden)

    Adapala Venkata J

    2012-04-01

    Full Text Available Abstract Background Inflammation in adipose tissue (AT during obesity causes impaired AT function. Although multiple extracellular matrix (ECM proteins are expressed in AT their potential role in adipose tissue inflammation is unclear. Biglycan, a pro-inflammatory ECM gene, is highly enriched in adipose tissue. However, whether it is correlated with adipose tissue inflammation is unknown. We provide evidence in support of a strong association between biglycan expression and inflammatory status of adipose tissue. Methods C57BL6 mice were fed either a control (10% fat calories or a high fat diet (HFD (60% fat calories for 8 weeks. Adipose tissue was analyzed for the expression of biglycan, IL-6 and TNFα. Biglycan knockout or wild type were also fed a high fat diet for 8 weeks and the expression of inflammatory genes in the mesenteric adipose tissue was examined. To test anti-inflammatory treatment on biglycan expression, a group of mice were fed either the low fat or high fat diet for eight weeks supplemented with either saline or sodium salicylate @ 25mg/100ml in their drinking water. Results Mice on HFD had an increase in ECM genes (BGN and COL1A1, inflammatory genes (IL-6 and TNFα in both the subcutaneous and epididymal depots. However, correlation analysis only shows a positive correlation between biglycan, IL-6 and TNFα expression. In addition, lower expression of IL-6 and CD68 was found in the mesenteric adipose tissue of biglycan knockout mice compared to the wild type. Sodium salicylate treatment reduced subcutaneous adipose tissue expression of BGN, COL1A1, and COL6A1 and a concurrent downregulation of TNFα and IL-6 and TLR4 expression. Salicylate also lowered the serum TGFβ1 levels. Conclusion Biglycan expression correlates with adipose tissue inflammation, especially in the subcutaneous depot compared to the epididymal depot. This is supported by the greater effect of sodium salicylate in attenuating both inflammatory and ECM gene

  19. [Role of chronic inflammation in adipose tissue in the pathophysiology of obesity].

    Science.gov (United States)

    Suganami, Takayoshi; Ogawa, Yoshihiro

    2013-02-01

    Obesity may be viewed as a chronic low-grade inflammatory disease as well as a metabolic disease. Evidence has accumulated suggesting that chronic inflammation in adipose tissue leads to dramatic changes in number and cell type of stromal cells during the course of obesity, which is referred to as"adipose tissue remodeling". Among stromal cells, macrophages in obese adipose tissue are considered to be crucial for adipose tissue inflammation, which results in dysregulated adipocytokine production and ectopic fat accumulation. Understanding the molecular mechanism underlying adipose tissue inflammation would contribute to the identification of novel therapeutic strategies to prevent or treat obesity-induced metabolic derangements.

  20. Bofutsushosan ameliorates obesity in mice through modulating PGC-1α expression in brown adipose tissues and inhibiting inflammation in white adipose tissues.

    Science.gov (United States)

    Chen, Ying-Ying; Yan, Yan; Zhao, Zheng; Shi, Mei-Jing; Zhang, Yu-Bin

    2016-06-01

    The inducible co-activator PGC-1α plays a crucial role in adaptive thermogenesis and increases energy expenditure in brown adipose tissue (BAT). Meanwhile, chronic inflammation caused by infiltrated-macrophage in the white adipose tissue (WAT) is a target for the treatment of obesity. Bofutsushosan (BF), a traditional Chinese medicine composed of 17 crude drugs, has been widely used to treat obesity in China, Japan, and other Asia countries. However, the mechanism underlying anti-obesity remains to be elucidated. In the present study, we demonstrated that BF oral administration reduced the body weight of obese mice induced by high-fat diet (HFD) and alleviated the level of biochemical markers (P obesity was at least partially through increasing gene expression of PGC-1α and UCP1 for energy consumption in BAT and inhibiting inflammation in WAT.

  1. Adipose tissue deletion of Gpr116 impairs insulin sensitivity through modulation of adipose function.

    Science.gov (United States)

    Nie, Tao; Hui, Xiaoyan; Gao, Xuefei; Li, Kuai; Lin, Wanhua; Xiang, Xiaoliang; Ding, Mengxiao; Kuang, Ying; Xu, Aimin; Fei, Jian; Wang, Zhugang; Wu, Donghai

    2012-10-19

    G protein-coupled receptor 116 (GPR116) is a novel member of the G protein-coupled receptors and its function is largely unknown. To investigate the physiological function of GPR116 in vivo, we generated adipose tissue specific conditional Gpr116 knockout mice (CKO) and fed them on standard chow or high fat diets. Selective deletion of Gpr116 in adipose tissue caused a pronounced glucose intolerance and insulin resistance in mice, especially when challenged with a high fat diet. Biochemical analysis revealed a more severe hepatosteatosis in CKO mice. Additionally, we found that CKO mice showed a lowered concentration of circulating adiponectin and an increased level of serum resistin. Our study suggests that GPR116 may play a critical role in controlling adipocyte biology and systemic energy homeostasis. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.

  2. Succination of Thiol Groups in Adipose Tissue Proteins in Diabetes

    Science.gov (United States)

    Frizzell, Norma; Rajesh, Mathur; Jepson, Matthew J.; Nagai, Ryoji; Carson, James A.; Thorpe, Suzanne R.; Baynes, John W.

    2009-01-01

    S-(2-Succinyl)cysteine (2SC) is formed by reaction of the Krebs cycle intermediate fumarate with cysteine residues in protein, a process termed succination of protein. Both fumarate and succination of proteins are increased in adipocytes cultured in high glucose medium (Nagai, R., Brock, J. W., Blatnik, M., Baatz, J. E., Bethard, J., Walla, M. D., Thorpe, S. R., Baynes, J. W., and Frizzell, N. (2007) J. Biol. Chem. 282, 34219–34228). We show here that succination of protein is also increased in epididymal, mesenteric, and subcutaneous adipose tissue of diabetic (db/db) mice and that adiponectin is a major target for succination in both adipocytes and adipose tissue. Cys-39, which is involved in cross-linking of adiponectin monomers to form trimers, was identified as a key site of succination of adiponectin in adipocytes. 2SC was detected on two of seven monomeric forms of adiponectin immunoprecipitated from adipocytes and epididymal adipose tissue. Based on densitometry, 2SC-adiponectin accounted for ∼7 and 8% of total intracellular adiponectin in cells and tissue, respectively. 2SC was found only in the intracellular, monomeric forms of adiponectin and was not detectable in polymeric forms of adiponectin in cell culture medium or plasma. We conclude that succination of adiponectin blocks its incorporation into trimeric and higher molecular weight, secreted forms of adiponectin. We propose that succination of proteins is a biomarker of mitochondrial stress and accumulation of Krebs cycle intermediates in adipose tissue in diabetes and that succination of adiponectin may contribute to the decrease in plasma adiponectin in diabetes. PMID:19592500

  3. [The adipose tissue as a regulatory center of the metabolism].

    Science.gov (United States)

    Fonseca-Alaniz, Miriam H; Takada, Julie; Alonso-Vale, Maria Isabel C; Lima, Fabio Bessa

    2006-04-01

    The recent progress in the research about the metabolic properties of the adipose tissue and the discovery of its ability to produce hormones that are very active in pathophysiologic as well as physiologic processes is rebuilding the concepts about its biology. Its involvement in conditions like obesity, type 2 diabetes mellitus, arterial hypertension, arteriosclerosis, dislipidemias and chronic and acute inflammatory processes indicate that the understanding of its functional capacities may contribute to improve the prognosis of those diseases whose prevalence increased in a preoccupying manner. Here we review some functional aspects of adipocytes, such as the metabolism, its influence on energy homeostasis, its endocrine ability and the adipogenesis, i.e., the potential of pre-adipocytes present in adipose tissue stroma to differentiate into new adipocytes and regenerate the tissue. In addition, we are including some studies on the relationship between the adipose tissue and the pineal gland, a new and poorly known, although, as will be seen, very promising aspect of adipocyte physiology together with its possible favorable repercussions to the therapy of the obesity related diseases.

  4. Niacin increases adiponectin and decreases adipose tissue inflammation in high fat diet-fed mice.

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    Desiree Wanders

    Full Text Available AIMS: To determine the effects of niacin on adiponectin and markers of adipose tissue inflammation in a mouse model of obesity. MATERIALS AND METHODS: Male C57BL/6 mice were placed on a control or high-fat diet (HFD and were maintained on such diets for the duration of the study. After 6 weeks on the control or high fat diets, vehicle or niacin treatments were initiated and maintained for 5 weeks. Identical studies were conducted concurrently in HCA2 (-/- (niacin receptor(-/- mice. RESULTS: Niacin increased serum concentrations of the anti-inflammatory adipokine, adiponectin by 21% in HFD-fed wild-type mice, but had no effect on lean wild-type or lean or HFD-fed HCA2 (-/- mice. Niacin increased adiponectin gene and protein expression in the HFD-fed wild-type mice only. The increases in adiponectin serum concentrations, gene and protein expression occurred independently of changes in expression of PPARγ C/EBPα or SREBP-1c (key transcription factors known to positively regulate adiponectin gene transcription in the adipose tissue. Further, niacin had no effect on adipose tissue expression of ERp44, Ero1-Lα, or DsbA-L (key ER chaperones involved in adiponectin production and secretion. However, niacin treatment attenuated HFD-induced increases in adipose tissue gene expression of MCP-1 and IL-1β in the wild-type HFD-fed mice. Niacin also reduced the expression of the pro-inflammatory M1 macrophage marker CD11c in HFD-fed wild-type mice. CONCLUSIONS: Niacin treatment attenuates obesity-induced adipose tissue inflammation through increased adiponectin and anti-inflammatory cytokine expression and reduced pro-inflammatory cytokine expression in a niacin receptor-dependent manner.

  5. A role of active brown adipose tissue in cancer cachexia?

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    Emiel Beijer

    2012-06-01

    Full Text Available Until a few years ago, adult humans were not thought to have brown adipose tissue (BAT. Now, this is a rapidly evolving field of research with perspectives in metabolic syndromes such as obesity and new therapies targeting its bio-energetic pathways. White, brown and socalled brite adipose fat seem to be able to trans-differentiate into each other, emphasizing the dynamic nature of fat tissue for metabolism. Human and animal data in cancer cachexia to date provide some evidence for BAT activation, but its quantitative impact on energy expenditure and weight loss is controversial. Prospective clinical studies can address the potential role of BAT in cancer cachexia using 18F-fluorodeoxyglucose positron emission tomography-computed tomography scanning, with careful consideration of co-factors such as diet, exposure to the cold, physical activity and body mass index, that all seem to act on BAT recruitment and activity.

  6. Endogenous adipose tissue as a hemostatic: use in microsurgery.

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    Akelina, Yelena; Danilo, Peter

    2008-01-01

    Bleeding is a frequent complication of microsurgical repair of small blood vessels and time is spent while hemostasis is accomplished. We studied the hemostatic effect of endogenous adipose tissue on bleeding from rat femoral arterial anastomoses. We measured bleeding time (time from removal of clamps to cessation of active bleeding) and mean arterial blood velocity (using a micro-Doppler system), the latter immediately after anastomosis, and again 7 days post-anastomosis. Bleeding time for vessels with fat applied to the artery was 50% less than when no fat was applied. Blood velocity by day 7 post-anastomosis returned to values equivalent to those for intact arteries. Histological evaluation of the anastomotic site demonstrated no significant differences in inflammatory response between fat-treated and untreated arteries. These data suggest that endogenous adipose tissue may be a useful hemostatic agent devoid of significant effects on small artery blood velocity or histology. (c) 2008 Wiley-Liss, Inc.

  7. Id transcriptional regulators in adipogenesis and adipose tissue metabolism.

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    Patil, Mallikarjun; Sharma, Bal Krishan; Satyanarayana, Ande

    2014-06-01

    Id proteins (Id1-Id4) are helix-loop-helix (HLH) transcriptional regulators that lack a basic DNA binding domain. They act as negative regulators of basic helix-loop-helix (bHLH) transcription factors by forming heterodimers and inhibit their DNA binding and transcriptional activity. Id proteins are implicated in the regulation of various cellular mechanisms such as cell proliferation, cellular differentiation, cell fate determination, angiogenesis and tumorigenesis. A handful of recent studies also disclosed that Id proteins have critical functions in adipocyte differentiation and adipose tissue metabolism. Here, we reviewed the progress made thus far in understanding the specific functions of Id proteins in adipose tissue differentiation and metabolism. In addition to reviewing the known mechanisms of action, we also discuss possible additional mechanisms in which Id proteins might participate in regulating adipogenic and metabolic pathways.

  8. Lsd1 Ablation Triggers Metabolic Reprogramming of Brown Adipose Tissue

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    Delphine Duteil

    2016-10-01

    Full Text Available Previous work indicated that lysine-specific demethylase 1 (Lsd1 can positively regulate the oxidative and thermogenic capacities of white and beige adipocytes. Here we investigate the role of Lsd1 in brown adipose tissue (BAT and find that BAT-selective Lsd1 ablation induces a shift from oxidative to glycolytic metabolism. This shift is associated with downregulation of BAT-specific and upregulation of white adipose tissue (WAT-selective gene expression. This results in the accumulation of di- and triacylglycerides and culminates in a profound whitening of BAT in aged Lsd1-deficient mice. Further studies show that Lsd1 maintains BAT properties via a dual role. It activates BAT-selective gene expression in concert with the transcription factor Nrf1 and represses WAT-selective genes through recruitment of the CoREST complex. In conclusion, our data uncover Lsd1 as a key regulator of gene expression and metabolic function in BAT.

  9. Mechanisms of perivascular adipose tissue dysfunction in obesity.

    Science.gov (United States)

    Fernández-Alfonso, Maria S; Gil-Ortega, Marta; García-Prieto, Concha F; Aranguez, Isabel; Ruiz-Gayo, Mariano; Somoza, Beatriz

    2013-01-01

    Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT) was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity.

  10. Mechanisms of Perivascular Adipose Tissue Dysfunction in Obesity

    Directory of Open Access Journals (Sweden)

    Maria S. Fernández-Alfonso

    2013-01-01

    Full Text Available Most blood vessels are surrounded by adipose tissue. Similarly to the adventitia, perivascular adipose tissue (PVAT was considered only as a passive structural support for the vasculature, and it was routinely removed for isolated blood vessel studies. In 1991, Soltis and Cassis demonstrated for the first time that PVAT reduced contractions to noradrenaline in rat aorta. Since then, an important number of adipocyte-derived factors with physiological and pathophysiological paracrine vasoactive effects have been identified. PVAT undergoes structural and functional changes in obesity. During early diet-induced obesity, an adaptative overproduction of vasodilator factors occurs in PVAT, probably aimed at protecting vascular function. However, in established obesity, PVAT loses its anticontractile properties by an increase of contractile, oxidative, and inflammatory factors, leading to endothelial dysfunction and vascular disease. The aim of this review is to focus on PVAT dysfunction mechanisms in obesity.

  11. Prolactin (PRL) in adipose tissue: regulation and functions.

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    Ben-Jonathan, Nira; Hugo, Eric

    2015-01-01

    New information concerning the effects of prolactin (PRL) on metabolic processes warrants reevaluation of its overall metabolic actions. PRL affects metabolic homeostasis by regulating key enzymes and transporters associated with glucose and lipid metabolism in several target organs. In the lactating mammary gland, PRL increases the production of milk proteins, lactose, and lipids. In adipose tissue, PRL generally suppresses lipid storage and adipokine release and affect adipogenesis. A specific case is made for PRL in the human breast and adipose tissues, where it acts as a circulating hormone and an autocrine/paracrine factor. Although its overall effects on body composition are both modest and species-specific, PRL may be involved in the manifestation of insulin resistance.

  12. The metabolic effects of growth hormone in adipose tissue.

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    Chaves, Valéria Ernestânia; Júnior, Fernando Mesquita; Bertolini, Gisele Lopes

    2013-10-01

    There is a general consensus that a reduction in growth hormone (GH) secretion results in obesity. However, the pathophysiologic role of GH in the metabolism of lipids is yet to be fully understood. The major somatic targets of GH are bones and muscles, but GH stimulates lipolysis and seems to regulate lipid deposition in adipose tissue. Patients with isolated GH deficiency (GHD) have enlarged fat depots due to higher fat cell volume, but their fat cell numbers are lower than those of matched controls. The treatment of patients with GH results in a relative loss of body fat and shifts both fat cell number and fat cell volume toward normal, indicating an adipogenic effect of GH. Adults with GHD are characterized by perturbations in body composition, lipid metabolism, cardiovascular risk profile, and bone mineral density. It is well established that GHD is usually accompanied by an increase in fat accumulation; GH replacement in GHD results in the reduction of fat mass, particularly abdominal fat mass. In addition, abdominal obesity results in a secondary reduction in GH secretion that is reversible with weight loss. However, whereas GH replacement in patients with GHD leads to specific depletion of intra-abdominal fat, administering GH to obese individuals does not seem to result in a consistent reduction or redistribution of body fat. Although administering GH to obese non-GHD subjects has only led to equivocal results, more recent studies indicate that GH still remains a plausible metabolic candidate.

  13. Molecular clock integration of brown adipose tissue formation and function.

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    Nam, Deokhwa; Yechoor, Vijay K; Ma, Ke

    2016-01-01

    The circadian clock is an essential time-keeping mechanism that entrains internal physiology to environmental cues. Despite the well-established link between the molecular clock and metabolic homeostasis, an intimate interplay between the clock machinery and the metabolically active brown adipose tissue (BAT) is only emerging. Recently, we came to appreciate that the formation and metabolic functions of BAT, a key organ for body temperature maintenance, are under an orchestrated circadian clock regulation. Two complementary studies from our group uncover that the cell-intrinsic clock machinery exerts concerted control of brown adipogenesis with consequent impacts on adaptive thermogenesis, which adds a previously unappreciated temporal dimension to the regulatory mechanisms governing BAT development and function. The essential clock transcriptional activator, Bmal1, suppresses adipocyte lineage commitment and differentiation, whereas the clock repressor, Rev-erbα, promotes these processes. This newly discovered temporal mechanism in fine-tuning BAT thermogenic capacity may enable energy utilization and body temperature regulation in accordance with external timing signals during development and functional recruitment. Given the important role of BAT in whole-body metabolic homeostasis, pharmacological interventions targeting the BAT-modulatory activities of the clock circuit may offer new avenues for the prevention and treatment of metabolic disorders, particularly those associated with circadian dysregulation.

  14. The Expression of Adipogenic Genes in Adipose Tissues of Feedlot Steers Fed Supplementary Palm Oil or Soybean Oil.

    Science.gov (United States)

    Choi, Seong Ho; Park, Sung Kwon; Choi, Chang Weon; Li, Xiang Zi; Kim, Kyoung Hoon; Kim, Won Young; Jeong, Joon; Johnson, Bradley J; Zan, Linsen; Smith, Stephen B

    2016-03-01

    We hypothesized that supplementing finishing diets with palm oil would promote adipogenic gene expression and stearoyl-CoA desaturase (SCD) gene expression in subcutaneous (s.c.) and intramuscular (i.m.) adipose tissues of feedlot steers. Eighteen Angus and Angus crossbred steers were assigned to three groups of 6 steers and fed a basal diet (control), with 3% palm oil, or with 3% soybean oil, for 70 d, top-dressed daily. Tailhead s.c. adipose tissue was obtained by biopsy at 14 d before the initiation of dietary treatments and at 35 d of dietary treatments. At slaughter, after 70 d of dietary treatment, tailhead s.c. adipose tissue and i.m. adipose tissue were obtained from the longissimus thoracis muscle. Palm oil increased plasma palmitic acid and soybean oil increased plasma linoleic acid and α-linolenic acid relative to the initial sampling time. Expression of AMP-activated protein kinase alpha (AMPKα) and peroxisome proliferator-activated receptor gamma (PPARγ) increased between the initial and intermediate biopsies and declined thereafter (padipose tissue than in s.c. adipose tissue (padipose tissue of palm oil-fed steers than in control steers (p = 0.04) and CCAAT enhancer binding protein-beta (CEBPβ) gene expression was less in s.c. and i.m. adipose tissues of palm oil-fed steers than in soybean oil-fed steers (padipose tissue (p = 0.05); SCD gene expression in palm oil-fed steers was intermediate between control and soybean oil-fed steers. Contrary to our original hypothesis, palm oil did not promote adipogenic gene expression in s.c. and i.m. adipose tissue.

  15. Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

    OpenAIRE

    Scotney, Hannah; Symonds, Michael E; Law, James; Budge, Helen; Sharkey, Don; Manolopoulos, Konstantinos N.

    2017-01-01

    Introduction: Brown adipose tissue (BAT) is a thermogenic organ with substantial metabolic capacity and has important roles in the maintenance of body weight and metabolism. Regulation of BAT is primarily mediated through the ß-adrenoceptor (ß-AR) pathway. The in vivo endocrine regulation of this pathway in humans is unkown. The objective of our study was to assess the in vivo BAT temperature responses to acute glucocorticoid administration.\\ud Methods: We studied 8 healthy male volunteers, n...

  16. Sleep deprivation affects inflammatory marker expression in adipose tissue

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    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.

  17. CTLA-4Ig immunotherapy of obesity-induced insulin resistance by manipulation of macrophage polarization in adipose tissues.

    Science.gov (United States)

    Fujii, Masakazu; Inoguchi, Toyoshi; Batchuluun, Battsetseg; Sugiyama, Naonobu; Kobayashi, Kunihisa; Sonoda, Noriyuki; Takayanagi, Ryoichi

    2013-08-16

    It has been established that obesity alters the metabolic and endocrine function of adipose tissue and, together with accumulation of adipose tissue macrophages, contributes to insulin resistance. Although numerous studies have reported that shifting the polarization of macrophages from M1 to M2 can alleviate adipose tissue inflammation, manipulation of macrophage polarization has not been considered as a specific therapy. Here, we determined whether cytotoxic T-lymphocyte-associated antigen-4IgG1 (CTLA-4Ig) can ameliorate insulin resistance by induction of macrophages from proinflammatory M1 to anti-inflammatory M2 polarization in the adipose tissues of high fat diet-induced insulin-resistant mice. CTLA4-Ig treatment prevented insulin resistance by changing gene expression to M2 polarization, which increased the levels of arginase 1. Furthermore, flow cytometric analysis confirmed the alteration of polarization from CD11c (M1)- to CD206 (M2)-positive cells. Concomitantly, CTLA-4Ig treatment resulted in weight reductions of epididymal and subcutaneous adipose tissues, which may be closely related to overexpression of apoptosis inhibitors in macrophages. Moreover, proinflammatory cytokine and chemokine levels decreased significantly. In contrast, CCAAT enhancer binding protein α, peroxisome proliferator-activated receptor γ, and adiponectin expression increased significantly in subcutaneous adipose tissue. This novel mechanism of CTLA-4lg immunotherapy may lead to an ideal anti-obesity/inflammation/insulin resistance agent. Copyright © 2013 Elsevier Inc. All rights reserved.

  18. Nitro-fatty acid pharmacokinetics in the adipose tissue compartment.

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    Fazzari, Marco; Khoo, Nicholas K H; Woodcock, Steven R; Jorkasky, Diane K; Li, Lihua; Schopfer, Francisco J; Freeman, Bruce A

    2017-02-01

    Electrophilic nitro-FAs (NO2-FAs) promote adaptive and anti-inflammatory cell signaling responses as a result of an electrophilic character that supports posttranslational protein modifications. A unique pharmacokinetic profile is expected for NO2-FAs because of an ability to undergo reversible reactions including Michael addition with cysteine-containing proteins and esterification into complex lipids. Herein, we report via quantitative whole-body autoradiography analysis of rats gavaged with radiolabeled 10-nitro-[(14)C]oleic acid, preferential accumulation in adipose tissue over 2 weeks. To better define the metabolism and incorporation of NO2-FAs and their metabolites in adipose tissue lipids, adipocyte cultures were supplemented with 10-nitro-oleic acid (10-NO2-OA), nitro-stearic acid, nitro-conjugated linoleic acid, and nitro-linolenic acid. Then, quantitative HPLC-MS/MS analysis was performed on adipocyte neutral and polar lipid fractions, both before and after acid hydrolysis of esterified FAs. NO2-FAs preferentially incorporated in monoacyl- and diacylglycerides, while reduced metabolites were highly enriched in triacylglycerides. This differential distribution profile was confirmed in vivo in the adipose tissue of NO2-OA-treated mice. This pattern of NO2-FA deposition lends new insight into the unique pharmacokinetics and pharmacologic actions that could be expected for this chemically-reactive class of endogenous signaling mediators and synthetic drug candidates.

  19. Caveolae, lipid droplets, and adipose tissue biology: pathophysiological aspects.

    Science.gov (United States)

    Martin, Sally

    2013-09-01

    Adipocytes are specialized cells that function to store energy in the form of lipids, predominantly triglycerides (TGs), and as a regulatory system contributing to metabolic homoeostasis through the production and secretion of hormones and cytokines. The regulation of lipid homeostasis by adipose tissue is an important aspect of whole-body metabolism. Owing to the central nature of adipose tissue in lipid metabolism, dysregulation has wide-ranging effects, contributing to disorders as diverse as diabetes, cardiovascular disease, cancer, and neurodegeneration. Excess lipids are stored in specialized organelles called lipid droplets (LDs). The surface of the lipid droplet can be considered a highly regulated membrane domain that both protects the contents of the LD from unregulated lipolysis and the cell from the cytotoxic effects of elevated free fatty acids. The surface of the LD is coated with a variety of regulatory proteins, either resident or transiently associated, including enzymes involved in the breakdown of TG, lipid transport proteins, and cofactors. Recent studies have begun to unravel the range of LD-associated proteins and to define their functional significance. Importantly, the involvement of LD proteins in pathophysiological disorders is beginning to be understood. This review will outline recent advances in defining the diversity of LD-associated proteins and their links to metabolic disorders including the integral membrane protein, caveolin-1 (CAV1). Analysis of the role of CAV1 in adipose tissue has highlighted the interconnectedness between the regulation of lipid storage and the function of the adipocyte plasma membrane.

  20. Food consumption and adipose tissue DDT levels in Mexican women

    Directory of Open Access Journals (Sweden)

    Galván-Portillo Marcia

    2002-01-01

    Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

  1. Adipose tissue-derived stromal cells express neuronal phenotypes

    Institute of Scientific and Technical Information of China (English)

    杨立业; 刘相名; 孙兵; 惠国桢; 费俭; 郭礼和

    2004-01-01

    Background Adipose tissue-derived stromal cells (ADSCs) can be greatly expanded in vitro, and induced to differentiate into multiple mesenchymal cell types, including osteogenic, chondrogenic, myogenic, and adipogenic cells. This study was designed to investigate the possibility of ADSCs differentiating into neurons.Methods Adipose tissue from rats was digested with collagenase, and adherent stromal cells were cultured. A medium containing a low concentration of fetal bovine serum was adopted to induce the cells to differentiate. ADSCs were identified by immunocytochemistry, and semi-quantitative RT-PCR was applied to detect mRNA expression of neurofilament 1 (NF1), nestin, and neuron-specific enolase (NSE).Results Nestin-positive cells were found occasionally among ADSCs. ADSCs were found to express NSE mRNA and nestin mRNA, but not NF1 mRNA. ADSCs could differentiate into neuron-like cells in a medium composed of a low concentration of fetal bovine serum, and these differentiated cells displayed complicated neuron-like morphologies.Conclusions The data support the hypothesis that adipose tissue contains stem cells capable of differentiating into neurons. These stem cells can overcome their mesenchymal commitment, and may represent an alternative autologous stem cell source for CNS cell transplantation.

  2. Food consumption and adipose tissue DDT levels in Mexican women

    Directory of Open Access Journals (Sweden)

    Marcia Galván-Portillo

    2002-04-01

    Full Text Available This article analyzes food consumption in relation to levels of DDE (the principal metabolite of DDT in the adipose tissue of 207 Mexican women residing in States with high and low exposure to DDT. Data on the women's dietary habits and childbearing history were obtained from a personal interview. Adipose tissue DDE levels were measured by gas-liquid chromatography and compared by analysis of variance (ANOVA and multiple linear regression. Adipose tissue DDE levels increased significantly with age (p = 0.005 and residence in coastal areas (p = 0.002 and non-significantly with the consumption of onion, cauliflower, prickly pear, squash blossoms, sweet corn, broad beans, chili pepper sauce, ham, and fish. Even so, during breastfeeding there was a non-significant reduction in these levels. The findings suggest that certain foods serve as vehicles for DDE residues and confirm that breastfeeding is a mechanism for the elimination of this insecticide, which accumulates over the years in the human body.

  3. Adipose tissue-liver axis in alcoholic liver disease

    Institute of Scientific and Technical Information of China (English)

    2016-01-01

    Alcoholic liver disease (ALD) remains an important healthproblem worldwide. The disease spectrum is featuredby early steatosis, steatohepatitis (steatosis with inflammatorycells infiltration and necrosis), with someindividuals ultimately progressing to fibrosis/cirrhosis.Although the disease progression is well characterized,no effective therapies are currently available for thetreatment in humans. The mechanisms underlying theinitiation and progression of ALD are multifactorial andcomplex. Emerging evidence supports that adiposetissue dysfunction contributes to the pathogenesis ofALD. In the first part of this review, we discuss themechanisms whereby chronic alcohol exposure contributedto adipose tissue dysfunction, including cell death,inflammation and insulin resistance. It has been longknown that aberrant hepatic methionine metabolismis a major metabolic abnormality induced by chronicalcohol exposure and plays an etiological role in thepathogenesis of ALD. The recent studies in our groupdocumented the similar metabolic effect of chronicalcohol drinking on methionine in adipose tissue. Inthe second part of this review, we also briefly discussthe recent research progress in the field with a focuson how abnormal methionine metabolism in adiposetissue contributes to adipose tissue dysfunction and liverdamage.

  4. Exercise and the Regulation of Adipose Tissue Metabolism.

    Science.gov (United States)

    Tsiloulis, Thomas; Watt, Matthew J

    2015-01-01

    Adipose tissue is a major regulator of metabolism in health and disease. The prominent roles of adipose tissue are to sequester fatty acids in times of energy excess and to release fatty acids via the process of lipolysis during times of high-energy demand, such as exercise. The fatty acids released during lipolysis are utilized by skeletal muscle to produce adenosine triphosphate to prevent fatigue during prolonged exercise. Lipolysis is controlled by a complex interplay between neuro-humoral regulators, intracellular signaling networks, phosphorylation events involving protein kinase A, translocation of proteins within the cell, and protein-protein interactions. Herein, we describe in detail the cellular and molecular regulation of lipolysis and how these processes are altered by acute exercise. We also explore the processes that underpin adipocyte adaptation to endurance exercise training, with particular focus on epigenetic modifications, control by microRNAs and mitochondrial adaptations. Finally, we examine recent literature describing how exercise might influence the conversion of traditional white adipose tissue to high energy-consuming "brown-like" adipocytes and the implications that this has on whole-body energy balance. © 2015 Elsevier Inc. All rights reserved.

  5. Regenerative repair of damaged meniscus with autologous adipose tissue-derived stem cells.

    Science.gov (United States)

    Pak, Jaewoo; Lee, Jung Hun; Lee, Sang Hee

    2014-01-01

    Mesenchymal stem cells (MSCs) are defined as pluripotent cells found in numerous human tissues, including bone marrow and adipose tissue. Such MSCs, isolated from bone marrow and adipose tissue, have been shown to differentiate into bone and cartilage, along with other types of tissues. Therefore, MSCs represent a promising new therapy in regenerative medicine. The initial treatment of meniscus tear of the knee is managed conservatively with nonsteroidal anti-inflammatory drugs and physical therapy. When such conservative treatment fails, an arthroscopic resection of the meniscus is necessary. However, the major drawback of the meniscectomy is an early onset of osteoarthritis. Therefore, an effective and noninvasive treatment for patients with continuous knee pain due to damaged meniscus has been sought. Here, we present a review, highlighting the possible regenerative mechanisms of damaged meniscus with MSCs (especially adipose tissue-derived stem cells (ASCs)), along with a case of successful repair of torn meniscus with significant reduction of knee pain by percutaneous injection of autologous ASCs into an adult human knee.

  6. Adipose Tissue Macrophages in Rheumatoid Arthritis: Prevalence, Disease Related Indicators, and Associations with Cardiometabolic Risk Factors.

    Science.gov (United States)

    Giles, Jon T; Ferrante, Antony W; Broderick, Rachel; Zartoshti, Afshin; Rose, Janine; Downer, Kendall; Zhang, Hui-Zhu; Winchester, Robert J

    2017-04-07

    Objective Adipose tissue macrophages (ATMs) are a potent source of inflammatory cytokines with profound effects on adipose tissue function, yet their potential role in rheumatoid arthritis (RA) pathobiology is largely unstudied. Methods Periumbilical subcutaneous adipose tissue was obtained from 36 RA patients and 22 non-RA controls frequency matched on demographics and BMI. Samples were stained for the macrophage marker CD68 and the average proportion of ATMs, crown-like structures (CLSs: peri-adipocyte aggregates of three or more ATMs), and fibrosis were compared between groups. Results The adjusted proportion of ATMs among all nucleated cells was 76% higher in RA vs. non-RA samples (37.7 vs. 21.3%, respectively; pleflunomide, and TNF inhibitors had a significantly lower proportion of ATMs compared with non-users. CLSs were significantly higher in patients seropositive for rheumatoid factor and those with C-reactive protein levels≥10 mg/L, and significantly lower among those treated with statins. Linear ATMs were significantly associated with whole-body insulin resistance, but not with serum lipids. Conclusions ATMs and CLSs were more abundant in RA and associated with systemic inflammation, autoimmunity, and whole-body insulin resistance, suggesting possible contributions to the RA disease process. Lower levels of ATMs and CLSs associated with specific RA treatments suggest that adipose tissue inflammation may be ameliorated by immunomodulation. This article is protected by copyright. All rights reserved.

  7. Effect of Human Adipose Tissue Mesenchymal Stem Cells on the Regeneration of Ovine Articular Cartilage.

    Science.gov (United States)

    Zorzi, Alessandro R; Amstalden, Eliane M I; Plepis, Ana Maria G; Martins, Virginia C A; Ferretti, Mario; Antonioli, Eliane; Duarte, Adriana S S; Luzo, Angela C M; Miranda, João B

    2015-11-09

    Cell therapy is a promising approach to improve cartilage healing. Adipose tissue is an abundant and readily accessible cell source. Previous studies have demonstrated good cartilage repair results with adipose tissue mesenchymal stem cells in small animal experiments. This study aimed to examine these cells in a large animal model. Thirty knees of adult sheep were randomly allocated to three treatment groups: CELLS (scaffold seeded with human adipose tissue mesenchymal stem cells), SCAFFOLD (scaffold without cells), or EMPTY (untreated lesions). A partial thickness defect was created in the medial femoral condyle. After six months, the knees were examined according to an adaptation of the International Cartilage Repair Society (ICRS 1) score, in addition to a new Partial Thickness Model scale and the ICRS macroscopic score. All of the animals completed the follow-up period. The CELLS group presented with the highest ICRS 1 score (8.3 ± 3.1), followed by the SCAFFOLD group (5.6 ± 2.2) and the EMPTY group (5.2 ± 2.4) (p = 0.033). Other scores were not significantly different. These results suggest that human adipose tissue mesenchymal stem cells promoted satisfactory cartilage repair in the ovine model.

  8. Hypoxic Living and Exercise Training Alter Adipose Tissue Leptin/Leptin Receptor in Rats.

    Science.gov (United States)

    Lu, Yingli; Feng, Lianshi; Xie, Minhao; Zhang, Li; Xu, Jianfang; He, Zihong; You, Tongjian

    2016-01-01

    Background: Hypobaric hypoxia results in weight loss in obese individuals, and exercise training is advocated for the treatment of obesity and its related metabolic dysfunctions. The purpose of this study was to investigate the effects of hypoxic living and exercise training on obesity and adipose tissue leptin/leptin receptor in dietary-induced obese rats. Methods: One hundred and thirty high-fat diet fed Sprague-Dawley rats were assigned into one of the following groups (n = 10 each): control, sedentary hypoxic living for 1-4 weeks (SH1, SH2, SH3, and SH4), living, and exercise training in normoxic conditions for 1-4 weeks (TN1, TN2, TN3, and TN4), and living and exercise training in hypoxic conditions for 1-4 weeks (TN1, TN2, TN3, and TN4). Epididymal adipose tissue expression levels of leptin and leptin receptor were determined Results: Compared to hypoxic living and living and exercise training in normoxic conditions, living and exercise training in hypoxic conditions for 3-4 weeks resulted in lower Lee index (P leptin and leptin receptor (P adipose tissue. Conclusion: In a rodent model of altitude training, living, and exercise training in hypoxic conditions resulted in greater alterations in obesity and adipose tissue leptin/leptin receptor than hypoxic living alone and living and exercise training in normoxic conditions.

  9. Microbiota depletion promotes browning of white adipose tissue and reduces obesity.

    Science.gov (United States)

    Suárez-Zamorano, Nicolas; Fabbiano, Salvatore; Chevalier, Claire; Stojanović, Ozren; Colin, Didier J; Stevanović, Ana; Veyrat-Durebex, Christelle; Tarallo, Valentina; Rigo, Dorothée; Germain, Stéphane; Ilievska, Miroslava; Montet, Xavier; Seimbille, Yann; Hapfelmeier, Siegfried; Trajkovski, Mirko

    2015-12-01

    Brown adipose tissue (BAT) promotes a lean and healthy phenotype and improves insulin sensitivity. In response to cold or exercise, brown fat cells also emerge in the white adipose tissue (WAT; also known as beige cells), a process known as browning. Here we show that the development of functional beige fat in the inguinal subcutaneous adipose tissue (ingSAT) and perigonadal visceral adipose tissue (pgVAT) is promoted by the depletion of microbiota either by means of antibiotic treatment or in germ-free mice. This leads to improved glucose tolerance and insulin sensitivity and decreased white fat and adipocyte size in lean mice, obese leptin-deficient (ob/ob) mice and high-fat diet (HFD)-fed mice. Such metabolic improvements are mediated by eosinophil infiltration, enhanced type 2 cytokine signaling and M2 macrophage polarization in the subcutaneous white fat depots of microbiota-depleted animals. The metabolic phenotype and the browning of the subcutaneous fat are impaired by the suppression of type 2 cytokine signaling, and they are reversed by recolonization of the antibiotic-treated or germ-free mice with microbes. These results provide insight into the microbiota-fat signaling axis and beige-fat development in health and metabolic disease.

  10. Phosphatase and Tension Homolog Overexpression in Insulin Resistant Diabetic Adipose Tissue

    Institute of Scientific and Technical Information of China (English)

    Jing-bo Zeng; Yun Zhang; Qi Sun; and Yu-xiu Li

    2014-01-01

    Objective To investigate the expression of phosphatase and tension homolog (PTEN) in adipose tissue of KKAy diabetic mice, a mouse model of type 2 diabetes. Methods KKAy diabetic mice were fed with high fat diet for 4 weeks. After blood glucose met the criteria of diabetes (over 16.7 mmol/L), mice were randomly divided into 3 groups:a control group (without any treatment), a rosiglitazone group (treated with rosiglitazone 12.5 mg/kg·d once per day), and a metformin group (treated with metformin 3 g/kg·d twice daily). After 4 weeks, we then determined the expression of PTEN and phosphoserine 473-Akt (pS473-Akt) in the epididymal adipose tissue with Western blots. The mice in each group were further divided into the insulin (-) subgroup and insulin (+) subgroup, which were intraperitoneally injected with saline and insulin (5 mU/g body weight), respectively. Results The expression of PTEN was elevated in the epididymal adipose tissue obtained from KKAy diabetic mice compared with that from the C57BL/6J mice (P Conclusion PTEN may play an important role in the development of insulin resistance in adipose tissue of type 2 diabetes mice model.

  11. The effects of thyroid hormones on brown adipose tissue in humans: a PET-CT study.

    Science.gov (United States)

    Zhang, Qiongyue; Miao, Qing; Ye, Hongying; Zhang, Zhaoyun; Zuo, Chuantao; Hua, Fengchun; Guan, Yihui; Li, Yiming

    2014-09-01

    Brown adipose tissue (BAT) is important for energy expenditure through thermogenesis, although its regulatory factors are not well known in humans. There is evidence suggesting that thyroid hormones affect BAT functions in some mammals, but the effects of thyroid hormones on BAT activity in humans are still unclear. The aim of this study was to investigate the effects of thyroid hormones on glucose metabolism of BAT and other organs in humans. Nine Graves' disease-caused hyperthyroid patients who were newly diagnosed and untreated were studied. Putative brown adipose tissue activity was determined by the integrated ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) positron-emission tomography and computed tomography (PET-CT). All hyperthyroid patients were treated with methimazole and had been monitored until their symptoms disappeared and thyroid hormone levels returned to normal. At the end, a second PET-CT scan was performed. The average follow-up period was 77 days. Meanwhile, compared with a group of seventy-five brown adipose tissue-negative controls, thyroid hormones of seventy-five BAT-positive healthy subjects were measured. Active brown adipose tissue was not present in any of the hyperthyroid patients. However, one patient with normalized thyroid function showed active BAT after therapy. The free T3 levels and free T4 levels were significantly lower in the 75 BAT-positive subjects than in the BAT-negative subjects. All hyperthyroid patients showed symmetrically increased uptake of fluorodeoxyglucose in skeletal muscles before treatment, whereas, the standardized uptake value was substantially decreased after treatment. Abnormally high circulating thyroid hormone levels may not increase brown adipose tissue activity, which may be limited by the increased obligatory thermogenesis of muscle in adult humans. Copyright © 2014 John Wiley & Sons, Ltd.

  12. Forkhead box A3 mediates glucocorticoid receptor function in adipose tissue.

    Science.gov (United States)

    Ma, Xinran; Xu, Lingyan; Mueller, Elisabetta

    2016-03-22

    Glucocorticoids (GCs) are widely prescribed anti-inflammatory agents, but their chronic use leads to undesirable side effects such as excessive expansion of adipose tissue. We have recently shown that the forkhead box protein A3 (Foxa3) is a calorie-hoarding factor that regulates the selective enlargement of epididymal fat depots and suppresses energy expenditure in a nutritional- and age-dependent manner. It has been demonstrated that Foxa3 levels are elevated in adipose depots in response to high-fat diet regimens and during the aging process; however no studies to date have elucidated the mechanisms that control Foxa3's expression in fat. Given the established effects of GCs in increasing visceral adiposity and in reducing thermogenesis, we assessed the existence of a possible link between GCs and Foxa3. Computational prediction analysis combined with molecular studies revealed that Foxa3 is regulated by the glucocorticoid receptor (GR) in preadipocytes, adipocytes, and adipose tissues and is required to facilitate the binding of the GR to its target gene promoters in fat depots. Analysis of the long-term effects of dexamethasone treatment in mice revealed that Foxa3 ablation protects mice specifically against fat accretion but not against other pathological side effects elicited by this synthetic GC in tissues such as liver, muscle, and spleen. In conclusion our studies provide the first demonstration, to our knowledge, that Foxa3 is a direct target of GC action in adipose tissues and point to a role of Foxa3 as a mediator of the side effects induced in fat tissues by chronic treatment with synthetic steroids.

  13. Periadventitial adipose tissue modulates the effect of PROLI/NO on neointimal hyperplasia.

    Science.gov (United States)

    Bahnson, Edward S M; Havelka, George E; Koo, Nathaniel C; Jiang, Qun; Kibbe, Melina R

    2016-10-01

    Periadventitial delivery of nitric oxide (NO) inhibits neointimal hyperplasia; however, the effect of periadventitial adipose tissue on the efficacy of NO at inhibiting neointimal hyperplasia has not been studied. The aim of our study was to assess the effect of NO in the presence and absence of periadventitial adipose tissue. We hypothesized that removal of periadventitial adipose tissue will increase neointimal formation and that NO will be more effective at inhibiting neointimal hyperplasia. The effect of NO on 3T3 fibroblasts, adventitial fibroblast (AF), and vascular smooth muscle cell (VSMC) proliferation was assessed by (3)H-thymidine incorporation in adipocyte-conditioned or regular media. The rat carotid artery balloon injury model was performed on male Sprague-Dawley rats. Before balloon injury, periadventitial adipose tissue was removed (excised model) or remained intact (intact model). Treatment groups included injury or injury with periadventitial application of PROLI/NO. Adiponectin receptor (AR) levels were assessed via immunofluorescence. Adipocyte-conditioned media had an antiproliferative effect on 3T3 and AF and a proproliferative effect on VSMC in vitro. Interestingly, NO was less effective at inhibiting 3T3 and AF proliferation and more effective at inhibiting VSMC proliferation in adipocyte-conditioned media. In vivo, the excised group showed increased neointimal hyperplasia 2 wk after surgery compared with the intact group. NO reduced neointimal hyperplasia to a greater extent in the excised group compared with the intact group. Although NO inhibited or had no impact on AR levels in the intact group, NO increased AR levels in media and adventitia of the excised group. These data show that periadventitial adipose tissue plays a role in regulating the arterial injury response and the efficacy of NO treatment in the vasculature. Published by Elsevier Inc.

  14. Broiler chicken adipose tissue dynamics during the first two weeks post-hatch.

    Science.gov (United States)

    Bai, Shiping; Wang, Guoqing; Zhang, Wei; Zhang, Shuai; Rice, Brittany Breon; Cline, Mark Andrew; Gilbert, Elizabeth Ruth

    2015-11-01

    Selection of broiler chickens for growth has led to increased adipose tissue accretion. To investigate the post-hatch development of adipose tissue, the abdominal, clavicular, and subcutaneous adipose tissue depots were collected from broiler chicks at 4 and 14 days post-hatch. As a percent of body weight, abdominal fat increased (Padipose development, with larger adipocytes and greater G3PDH activity in subcutaneous fat at day 4, more rapid growth of abdominal fat, and clavicular fat intermediate for most traits. Adipose tissue expansion was accompanied by changes in gene expression of adipose-associated factors.

  15. Expression and Regulation of Soluble Epoxide Hydrolase in Adipose Tissue

    Science.gov (United States)

    De Taeye, Bart M.; Morisseau, Christophe; Coyle, Julie; Covington, Joseph W.; Luria, Ayala; Yang, Jun; Murphy, Sheila B.; Friedman, David B.; Hammock, Bruce B.; Vaughan, Douglas E.

    2010-01-01

    Obesity is an increasingly important public health issue reaching epidemic proportions. Visceral obesity has been defined as an important element of the metabolic syndrome and expansion of the visceral fat mass has been shown to contribute to the development of insulin resistance and cardiovascular disease. To identify novel contributors to cardiovascular and metabolic abnormalities in obesity, we analyzed the adipose proteome and identified soluble epoxide hydrolase (sEH) in the epididymal fat pad from C57BL/6J mice that received either a regular diet or a “western diet.” sEH was synthesized in adipocytes and expression levels increased upon differentiation of 3T3-L1 preadipocytes. Although normalized sEH mRNA and protein levels did not differ in the fat pads from mice receiving a regular or a “western diet,” total adipose sEH activity was higher in the obese mice, even after normalization for body weight. Furthermore, peroxisome proliferator–activated recetor γ(PPARγ) agonists increased the expression of sEH in mature 3T3-L1 adipocytes in vitro and in adipose tissue in vivo. Considering the established role for sEH in inflammation, cardiovascular diseases, and lipid metabolism, and the suggested involvement of sEH in the development of type 2 diabetes, our study has identified adipose sEH as a potential novel therapeutic target that might affect the development of metabolic and cardiovascular abnormalities in obesity. PMID:19644452

  16. Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, J

    2010-01-01

    The adipose tissue metabolism is dependent on its blood perfusion. During lipid mobilization e.g. during exercise and during lipid deposition e.g. postprandial, adipose tissue blood flow is increased. This increase in blood flow may involve capillary recruitment in the tissue. We investigated...... the basic and postprandial microvascular volume in adipose tissue using real-time contrast-enhanced ultrasound (CEU) imaging in healthy normal weight subjects. In nine subjects, CEU was performed in abdominal subcutaneous adipose tissue and in the underlying skeletal muscle after a bolus injection...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain...

  17. Deep sequencing of the transcriptome reveals inflammatory features of porcine visceral adipose tissue.

    Science.gov (United States)

    Wang, Tao; Jiang, Anan; Guo, Yanqin; Tan, Ya; Tang, Guoqing; Mai, Miaomiao; Liu, Haifeng; Xiao, Jian; Li, Mingzhou; Li, Xuewei

    2013-01-01

    Functional differences in the different types of adipose tissue and the impact of their dysfunction on metabolism are associated with the regional distribution of adipose depots. Here we show a genome-wide comparison between the transcriptomes of one source of subcutaneous and two sources of visceral adipose tissue in the pig using an RNA-seq approach. We obtained ~32.3 million unique mapped reads which covered ~80.2% of the current annotated transcripts across these three sources of adipose tissue. We identified various genes differentially expressed between subcutaneous and visceral adipose tissue, which are potentially associated with the inflammatory features of visceral adipose tissue. These results are of benefit for understanding the phenotypic, metabolic and functional differences between different types of adipose tissue that are deposited in different body sites.

  18. Repairing nerve gaps by vein conduits filled with lipoaspirate-derived entire adipose tissue hinders nerve regeneration.

    Science.gov (United States)

    Papalia, Igor; Raimondo, Stefania; Ronchi, Giulia; Magaudda, Ludovico; Giacobini-Robecchi, Maria G; Geuna, Stefano

    2013-05-01

    In spite of great recent advancements, the definition of the optimal strategy for bridging a nerve defect, especially across long gaps, still remains an open issue since the amount of autologous nerve graft material is limited while the outcome after alternative tubulization techniques is often unsatisfactory. The aim of this study was to investigate a new tubulization technique based on the employment of vein conduits filled with whole subcutaneous adipose tissue obtained by lipoaspiration. In adult rats, a 1cm-long defect of the left median nerve was repaired by adipose tissue-vein-combined conduits and compared with fresh skeletal muscle tissue-vein-combined conduits and autologous nerve grafts made by the excised nerve segment rotated by 180°. Throughout the postoperative period, functional recovery was assessed using the grasping test. Regenerated nerve samples were withdrawn at postoperative month-6 and processed for light and electron microscopy and stereology of regenerated nerve fibers. Results showed that functional recovery was significantly slower in the adipose tissue-enriched group in comparison to both control groups. Light and electron microscopy showed that a large amount of adipose tissue was still present inside the vein conduits at postoperative month-6. Stereology showed that all quantitative morphological predictors analyzed performed significantly worse in the adipose tissue-enriched group in comparison to the two control groups. On the basis of this experimental study in the rat, the use of whole adipose tissue for tissue engineering of peripheral nerves should be discouraged. Pre-treatment of adipose tissue aimed at isolating stromal vascular fraction and/or adipose derived stem/precursor cells should be considered a fundamental requisite for nerve repair.

  19. Laser light propagation in adipose tissue and laser effects on adipose cell membranes

    Science.gov (United States)

    Solarte, Efraín; Rebolledo, Aldo; Gutierrez, Oscar; Criollo, William; Neira, Rodrigo; Arroyave, José; Ramírez, Hugo

    2006-01-01

    Recently Neira et al. have presented a new liposuction technique that demonstrated the movement of fat from inside to outside of the cell, using a low-level laser device during a liposuction procedure with Ultrawet solution. The clinical observations, allowed this new surgical development, started a set of physical, histological and pharmacological studies aimed to determine the mechanisms involved in the observed fat mobilization concomitant to external laser application in liposuction procedures. Scanning and Transmission Electron Microscopy, studies show that the cellular arrangement of normal adipose tissue changes when laser light from a diode laser: 10 mW, 635 nm is applied. Laser exposures longer than 6 minutes cause the total destruction of the adipocyte panicles. Detailed observation of the adipose cells show that by short irradiation times (less than four minutes) the cell membrane exhibits dark zones, that collapse by longer laser exposures. Optical measurements show that effective penetration length depends on the laser intensity. Moreover, the light scattering is enhanced by diffraction and subsequent interference effects, and the tumescent solution produces a clearing of the tissue optical medium. Finally, isolate adipose cell observation show that fat release from adipocytes is a concomitant effect between the tumescent solution (adrenaline) and laser light, revealing a synergism which conduces to the aperture, and maybe the disruption, of the cell membrane. All these studies were consistent with a laser induced cellular process, which causes fat release from inside the adipocytes into the intercellular space, besides a strong modification of the cellular membranes.

  20. Testosterone differentially regulates targets of lipid and glucose metabolism in liver, muscle and adipose tissues of the testicular feminised mouse.

    Science.gov (United States)

    Kelly, Daniel M; Akhtar, Samia; Sellers, Donna J; Muraleedharan, Vakkat; Channer, Kevin S; Jones, T Hugh

    2016-11-01

    Testosterone deficiency is commonly associated with obesity, metabolic syndrome, type 2 diabetes and their clinical consequences-hepatic steatosis and atherosclerosis. The testicular feminised mouse (non-functional androgen receptor and low testosterone) develops fatty liver and aortic lipid streaks on a high-fat diet, whereas androgen-replete XY littermate controls do not. Testosterone treatment ameliorates these effects, although the underlying mechanisms remain unknown. We compared the influence of testosterone on the expression of regulatory targets of glucose, cholesterol and lipid metabolism in muscle, liver, abdominal subcutaneous and visceral adipose tissue. Testicular feminised mice displayed significantly reduced GLUT4 in muscle and glycolytic enzymes in muscle, liver and abdominal subcutaneous but not visceral adipose tissue. Lipoprotein lipase required for fatty acid uptake was only reduced in subcutaneous adipose tissue; enzymes of fatty acid synthesis were increased in liver and subcutaneous tissue. Stearoyl-CoA desaturase-1 that catalyses oleic acid synthesis and is associated with insulin resistance was increased in visceral adipose tissue and cholesterol efflux components (ABCA1, apoE) were decreased in subcutaneous and liver tissue. Master regulator nuclear receptors involved in metabolism-Liver X receptor expression was suppressed in all tissues except visceral adipose tissue, whereas PPARγ was lower in abdominal subcutaneous and visceral adipose tissue and PPARα only in abdominal subcutaneous. Testosterone treatment improved the expression (androgen receptor independent) of some targets but not all. These exploratory data suggest that androgen deficiency may reduce the buffering capability for glucose uptake and utilisation in abdominal subcutaneous and muscle and fatty acids in abdominal subcutaneous. This would lead to an overspill and uptake of excess glucose and triglycerides into visceral adipose tissue, liver and arterial walls.

  1. Intrinsic regulation of blood flow in adipose tissue

    DEFF Research Database (Denmark)

    Henriksen, O; Nielsen, Steen Levin; Paaske, W

    1976-01-01

    Previous studies on intact human subcutaneous tissue have shown, that blood flow remains constant during minor changes in perfusion pressure. This so-called autoregulatory response has not been demonstrable in isolated preparations of adipose tissue. In the present study on isolated, denervated...... subcutaneous tissue in female rabbits only 2 of 12 expts. revealed an autoregulatory response during reduction in arterial perfusion pressure. Effluent blood flow from the tissue in the control state was 15.5 ml/100 g-min (S.D. 6.4, n = 12) corresponding to slight vasodilatation of the exposed tissue....... Following total ischemia all experiments showed a period with reactive hyperemia, and both duration of hyperemia and excess flow was related to the duration of the ischemia. This response therefore seems more resistant to the experimental procedure, while autoregulation of blood flow to lowered pressure...

  2. Adipose-derived stromal cells mediate in vivo adipogenesis, angiogenesis and inflammation in decellularized adipose tissue bioscaffolds.

    Science.gov (United States)

    Han, Tim Tian Y; Toutounji, Sandra; Amsden, Brian G; Flynn, Lauren E

    2015-12-01

    Decellularized adipose tissue (DAT) has shown promise as an adipogenic bioscaffold for soft tissue augmentation and reconstruction. The objective of the current study was to investigate the effects of allogeneic adipose-derived stem/stromal cells (ASCs) on in vivo fat regeneration in DAT bioscaffolds using an immunocompetent rat model. ASC seeding significantly enhanced angiogenesis and adipogenesis, with cell tracking studies indicating that the newly-forming tissues were host-derived. Incorporating ASCs also mediated the inflammatory response and promoted a more constructive macrophage phenotype. A fraction of the CD163(+) macrophages in the implants expressed adipogenic markers, with higher levels of this "adipocyte-like" phenotype in proximity to the developing adipose tissues. Our results indicate that the combination of ASCs and adipose extracellular matrix (ECM) provides an inductive microenvironment for adipose regeneration mediated by infiltrating host cell populations. The DAT scaffolds are a useful tissue-specific model system for investigating the mechanisms of in vivo adipogenesis that may help to develop a better understanding of this complex process in the context of both regeneration and disease. Overall, combining adipose-derived matrices with ASCs is a highly promising approach for the in situ regeneration of host-derived adipose tissue.

  3. Increased peroxisome proliferator-activated receptor γ expression levels in visceral adipose tissue, and serum CCL2 and interleukin-6 levels during visceral adipose tissue accumulation.

    Science.gov (United States)

    Yogarajah, Thaneswary; Bee, Yvonne-Tee Get; Noordin, Rahmah; Yin, Khoo Boon

    2015-01-01

    This study was conducted to determine the mRNA and protein expression levels of peroxisome proliferator-activated receptors (PPARs) in visceral adipose tissue, as well as serum adipokine levels, in Sprague Dawley rats. The rats were fed either a normal (control rats) or excessive (experimental rats) intake of food for 8 or 16 weeks, then sacrificed, at which time visceral and subcutaneous adipose tissues, as well as blood samples, were collected. The mRNA and protein expression levels of PPARs in the visceral adipose tissues were determined using reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, the levels of adipokines in the serum samples were determined using commercial ELISA kits. The results revealed that at 8 weeks, the mass of subcutaneous adipose tissue was higher than that of the visceral adipose tissue in the experimental rats, but the reverse occurred at 16 weeks. Furthermore, at 16 weeks the experimental rats exhibited an upregulation of PPARγ mRNA and protein expression levels in the visceral adipose tissues, and significant increases in the serum levels of CCL2 and interleukin (IL)-6 were observed, compared with those measured at 8 weeks. In conclusion, this study demonstrated that the PPARγ expression level was likely correlated with serum levels of CCL2 and IL-6, molecules that may facilitate visceral adipose tissue accumulation. In addition, the levels of the two adipokines in the serum may be useful as surrogate biomarkers for the expression levels of PPARγ in accumulated visceral adipose tissues.

  4. Identification of cathepsin K as a novel marker of adiposity in white adipose tissue.

    Science.gov (United States)

    Chiellini, Chiara; Costa, Mario; Novelli, Silvia E; Amri, Ez-Zoubir; Benzi, Luca; Bertacca, Anna; Cohen, Paul; Del Prato, Stefano; Friedman, Jeffrey M; Maffei, Margherita

    2003-05-01

    In obesity, adipocytes undergo dramatic morphological and molecular changes associated with alterations in their gene expression profile. To identify genes differentially modulated in white adipose tissue (WAT) of obese db/db mice compared to wild type (wt) mice, we utilized RNA fingerprinting. Among the 52 candidates that we identified, we focused here on cathepsin K (ctsk), a cysteine protease, prevalently localized in lysosomes and involved in bone extracellular matrix degradation. In db/db mice, WAT ctsk mRNA was elevated 5.9-fold, as were Mitf and TFE3 (2- and 3.3-fold respectively), two transcription factors involved in ctsk induction in osteoclasts. Moreover, the level of WAT ctsk mRNA was increased in other obese models including A(y), fat, and tubby (2.8-, 3.2-, and 4.9-fold respectively) and decreased in mice undergoing weight loss. Despite the ubiquitous distribution of the ctsk transcript, we demonstrated that the obesity related increase is specific to the adipocytes. Further, in vitro experiments proved that the abundance of ctsk transcript increases upon adipose conversion of the established cell line of preadipocytes 3T3-F442A. In addition, ctsk gene expression was examined in adipose tissue of 21 lean and obese male subjects and significant correlations with BMI (r = 0.54, P = 0.012) and plasma leptin levels (r = 0.54, P = 0.015) were found. In conclusion, the WAT of obese db/db mice exhibits a different expression profile from that of the wt mice, and cathepsin K can be considered a novel marker of obesity and a target for the inhibition of adipose mass growth.

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

    Science.gov (United States)

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

    2016-07-01

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

  6. Adipose tissue and ceramide biosynthesis in the pathogenesis of obesity.

    Science.gov (United States)

    Samad, Fahumiya; Badeanlou, Leylla; Shah, Charmi; Yang, Guang

    2011-01-01

    Although obesity is a complex metabolic disorder often associated with insulin resistance, hyperinsulinemia and Type 2 diabetes, as well as with accelerated atherosclerosis, the molecular changes in obesity that promote these disorders are not completely understood. Several mechanisms have been proposed to explain how increased adipose tissue mass affects whole body insulin resistance and cardiovascular risk. One theory is that increased adipose derived inflammatory cytokines induces a chronic inflammatory state that not only increases cardiovascular risk, but also antagonizes insulin signaling and mitochondrial function and thereby impair glucose hemostasis. Another suggests that lipid accumulation in nonadipose tissues not suited for fat storage leads to the buildup of bioactive lipids that inhibit insulin signaling and metabolism. Recent evidence demonstrates that sphingolipid metabolism is dysregulated in obesity and specific sphingolipids may provide a common pathway that link excess nutrients and inflammation to increased metabolic and cardiovascular risk. This chapter will focus primarily on the expression and regulation of adipose and plasma ceramide biosynthesis in obesity and, its potential contribution to the pathogenesis of obesity and the metabolic syndrome.

  7. Adipose tissue and vascular inflammation in coronary artery disease

    Institute of Scientific and Technical Information of China (English)

    Enrica; Golia; Giuseppe; Limongelli; Francesco; Natale; Fabio; Fimiani; Valeria; Maddaloni; Pina; Elvira; Russo; Lucia; Riegler; Renatomaria; Bianchi; Mario; Crisci; Gaetano; Di; Palma; Paolo; Golino; Maria; Giovanna; Russo; Raffaele; Calabrò; Paolo; Calabrò

    2014-01-01

    Obesity has become an important public health issue in Western and developing countries,with well known metabolic and cardiovascular complications.In the last decades,evidence have been growing about the active role of adipose tissue as an endocrine organ in determining these pathological consequences.As a consequence of the expansion of fat depots,in obese subjects,adipose tissue cells develope a phenotypic modification,which turns into a change of the secretory output.Adipocytokines produced by both adipocytes and adipose stromal cells are involved in the modulation of glucose and lipid handling,vascular biology and,moreover,participate to the systemic inflammatory response,which characterizes obesity and metabolic syndrome.This might represent an important pathophysiological link with atherosclerotic complications and cardiovascular events.A great number of adipocytokines have been described recently,linking inflammatory mileu and vascular pathology.The understanding of these pathways is crucial not only from a pathophysiological point of view,but also to a better cardiovascular disease risk stratification and to the identification of possible therapeutic targets.The aim of this paper is to review the role of Adipocytokines as a possible link between obesity and vascular disease.

  8. Mechanobiology and Mechanotherapy of Adipose Tissue-Effect of Mechanical Force on Fat Tissue Engineering.

    Science.gov (United States)

    Yuan, Yi; Gao, Jianhua; Ogawa, Rei

    2015-12-01

    Our bodies are subjected to various mechanical forces, which in turn affect both the structure and function of our bodies. In particular, these mechanical forces play an important role in tissue growth and regeneration. Adipocytes and adipose-derived stem cells are both mechanosensitive and mechanoresponsive. The aim of this review is to summarize the relationship between mechanobiology and adipogenesis. PubMed was used to search for articles using the following keywords: mechanobiology, adipogenesis, adipose-derived stem cells, and cytoskeleton. In vitro and in vivo experiments have shown that adipogenesis is strongly promoted/inhibited by various internal and external mechanical forces, and that these effects are mediated by changes in the cytoskeleton of adipose-derived stem cells and/or various signaling pathways. Thus, adipose tissue engineering could be enhanced by the careful application of mechanical forces. It was shown recently that mature adipose tissue regenerates in an adipose tissue-engineering chamber. This observation has great potential for the reconstruction of soft tissue deficiencies, but the mechanisms behind it remain to be elucidated. On the basis of our understanding of mechanobiology, we hypothesize that the chamber removes mechanical force on the fat that normally impose high cytoskeletal tension. The reduction in tension in adipose stem cells triggers their differentiation into adipocytes. The improvement in our understanding of the relationship between mechanobiology and adipogenesis means that in the near future, we may be able to increase or decrease body fat, as needed in the clinic, by controlling the tension that is loaded onto fat.

  9. Bone marrow–derived circulating progenitor cells fail to transdifferentiate into adipocytes in adult adipose tissues in mice

    Science.gov (United States)

    Koh, Young Jun; Kang, Shinae; Lee, Hyuek Jong; Choi, Tae-Saeng; Lee, Ho Sub; Cho, Chung-Hyun; Koh, Gou Young

    2007-01-01

    Little is known about whether bone marrow–derived circulating progenitor cells (BMDCPCs) can transdifferentiate into adipocytes in adipose tissues or play a role in expanding adipocyte number during adipose tissue growth. Using a mouse bone marrow transplantation model, we addressed whether BMDCPCs can transdifferentiate into adipocytes under standard conditions as well as in the settings of diet-induced obesity, rosiglitazone treatment, and exposure to G-CSF. We also addressed the possibility of transdifferentiation to adipocytes in a murine parabiosis model. In each of these settings, our findings indicated that BMDCPCs did not transdifferentiate into either unilocular or multilocular adipocytes in adipose tissues. Most BMDCPCs became resident and phagocytic macrophages in adipose tissues — which resembled transdifferentiated multilocular adipocytes by appearance, but displayed cell surface markers characteristic for macrophages — in the absence of adipocyte marker expression. When exposed to adipogenic medium in vitro, bone marrow cells differentiated into multilocular, but not unilocular, adipocytes, but transdifferentiation was not observed in vivo, even in the contexts of adipose tissue regrowth or dermal wound healing. Our results suggest that BMDCPCs do not transdifferentiate into adipocytes in vivo and play little, if any, role in expanding the number of adipocytes during the growth of adipose tissues. PMID:18060029

  10. Testosterone stimulates adipose tissue 11beta-hydroxysteroid dehydrogenase type 1 expression in a depot-specific manner in children.

    Science.gov (United States)

    Zhu, Lijun; Hou, Miao; Sun, Bin; Burén, Jonas; Zhang, Li; Yi, Jun; Hernell, Olle; Li, Xiaonan

    2010-07-01

    Activation of the enzyme 11beta-hydroxysteroid dehydrogenase type 1 (11beta-HSD1) in adipose tissue results in the production of excess tissue glucocorticoids and the induction of adiposity and visceral obesity in particular. Androgens may affect body fat distribution by regulating the local metabolism of cortisol. Our objective was to study 11beta-HSD1 mRNA expression in abdominal sc and omental (om) adipose tissue in children after in vitro testosterone and cortisol treatment. Paired fat biopsies (sc and om) were obtained from 19 boys (age 6-14 yr, body mass index 14.6-25.3 kg/m(2), BMI sd score SDS -1.6-3.1) undergoing open abdominal surgery. Pieces of adipose tissue were incubated with testosterone, cortisol, or both hormones for 24 h, whereupon mRNA expression of 11beta-HSD1 and hexose-6-phosphate dehydrogenase (H6PDH) were measured by real-time PCR, and 11beta-HSD1 enzyme activity was determined. Testosterone treatment up-regulated 11beta-HSD1 mRNA expression compared with control incubations in the absence of testosterone (P tissue. Testosterone and cortisol both increased 11beta-HSD1 mRNA expression in om but not sc adipose tissue in a depot-specific manner by 2.5- and 2.9-fold, respectively (P effect of the two hormones. 11beta-HSD1 enzyme activity correlated positively to mRNA expression (r = 0.610; P = 0.001). Adipose tissue mRNA expression of H6PDH was affected in a similar fashion to 11beta-HSD1 after hormonal treatment. Testosterone and cortisol stimulated 11beta-HSD1 and H6PDH mRNA expression and 11beta-HSD1 activity in om but not in sc adipose tissue. This suggests that these hormones may contribute to fat distribution and accumulation during childhood.

  11. Supercritical carbon dioxide extracted extracellular matrix material from adipose tissue.

    Science.gov (United States)

    Wang, Jun Kit; Luo, Baiwen; Guneta, Vipra; Li, Liang; Foo, Selin Ee Min; Dai, Yun; Tan, Timothy Thatt Yang; Tan, Nguan Soon; Choong, Cleo; Wong, Marcus Thien Chong

    2017-06-01

    Adipose tissue is a rich source of extracellular matrix (ECM) material that can be isolated by delipidating and decellularizing the tissue. However, the current delipidation and decellularization methods either involve tedious and lengthy processes or require toxic chemicals, which may result in the elimination of vital proteins and growth factors found in the ECM. Hence, an alternative delipidation and decellularization method for adipose tissue was developed using supercritical carbon dioxide (SC-CO2) that eliminates the need of any harsh chemicals and also reduces the amount of processing time required. The resultant SC-CO2-treated ECM material showed an absence of nuclear content but the preservation of key proteins such as collagen Type I, collagen Type III, collagen Type IV, elastin, fibronectin and laminin. In addition, other biological factors such as glycosaminoglycans (GAGs) and growth factors such as basic fibroblast growth factor (bFGF) and vascular endothelial growth factor (VEGF) were also retained. Subsequently, the resulting SC-CO2-treated ECM material was used as a bioactive coating on tissue culture plastic (TCP). Four different cell types including adipose tissue-derived mesenchymal stem cells (ASCs), human umbilical vein endothelial cells (HUVECs), immortalized human keratinocyte (HaCaT) cells and human monocytic leukemia cells (THP-1) were used in this study to show that the SC-CO2-treated ECM coating can be potentially used for various biomedical applications. The SC-CO2-treated ECM material showed improved cell-material interactions for all cell types tested. In addition, in vitro scratch wound assay using HaCaT cells showed that the presence of SC-CO2-treated ECM material enhanced keratinocyte migration whilst the in vitro cellular studies using THP-1-derived macrophages showed that the SC-CO2-treated ECM material did not evoke pro-inflammatory responses from the THP-1-derived macrophages. Overall, this study shows the efficacy of SC-CO2

  12. Real-time contrast-enhanced ultrasound determination of microvascular blood volume in abdominal subcutaneous adipose tissue in man. Evidence for adipose tissue capillary recruitment

    DEFF Research Database (Denmark)

    Tobin, L; Simonsen, L; Bülow, J

    2010-01-01

    the basic and postprandial microvascular volume in adipose tissue using real-time contrast-enhanced ultrasound (CEU) imaging in healthy normal weight subjects. In nine subjects, CEU was performed in abdominal subcutaneous adipose tissue and in the underlying skeletal muscle after a bolus injection...... of ultrasound contrast agent to establish the reproducibility of the technique. In nine subjects, the effect of an oral glucose load on blood flow and microvascular volume was measured in abdominal subcutaneous adipose tissue and forearm skeletal muscle. ¹³³Xe washout and venous occlusion strain......-gauge plethysmography was used to measure the adipose tissue and forearm blood flow, respectively. Ultrasound signal intensity of the first plateau phases was 27 ± dB in the abdominal subcutaneous adipose tissue and 18 ± 2 dB (P muscle. The reproducibility of the measurements was good...

  13. Regional differences in perivascular adipose tissue impacting vascular homeostasis.

    Science.gov (United States)

    Gil-Ortega, Marta; Somoza, Beatriz; Huang, Yu; Gollasch, Maik; Fernández-Alfonso, Maria S

    2015-07-01

    Perivascular adipose tissue (PVAT) releases several important vasoactive factors with physiological and pathophysiological paracrine effects. A large body of evidence suggests regional phenotypic and functional differences among PVAT depots, depending on the specific vascular bed or different regions in the vascular bed where the PVAT is located. These non-uniform and separate PVATs exert various paracrine effects on vascular structure and function that largely impact disease states, such as endothelial dysfunction, atherosclerosis, or insulin resistance. This emerging view of PVAT function requires considering heterogeneous PVAT as a specialized organ that can differentially regulate vascular function depending on its anatomical location. In this context, the adipose-vascular axis may represent a novel target for pharmacological intervention in vasculopathy in cardiometabolic disorders.

  14. Weight cycling enhances adipose tissue inflammatory responses in male mice.

    Directory of Open Access Journals (Sweden)

    Sandra Barbosa-da-Silva

    Full Text Available BACKGROUND: Obesity is associated with low-grade chronic inflammation attributed to dysregulated production, release of cytokines and adipokines and to dysregulated glucose-insulin homeostasis and dyslipidemia. Nutritional interventions such as dieting are often accompanied by repeated bouts of weight loss and regain, a phenomenon known as weight cycling (WC. METHODS: In this work we studied the effects of WC on the feed efficiency, blood lipids, carbohydrate metabolism, adiposity and inflammatory markers in C57BL/6 male mice that WC two or three consecutive times by alternation of a high-fat (HF diet with standard chow (SC. RESULTS: The body mass (BM grew up in each cycle of HF feeding, and decreased after each cycle of SC feeding. The alterations observed in the animals feeding HF diet in the oral glucose tolerance test, in blood lipids, and in serum and adipose tissue expression of adipokines were not recuperated after WC. Moreover, the longer the HF feeding was (two, four and six months, more severe the adiposity was. After three consecutive WC, less marked was the BM reduction during SC feeding, while more severe was the BM increase during HF feeding. CONCLUSION: In conclusion, the results of the present study showed that both the HF diet and WC are relevant to BM evolution and fat pad remodeling in mice, with repercussion in blood lipids, homeostasis of glucose-insulin and adipokine levels. The simple reduction of the BM during a WC is not able to recover the high levels of adipokines in the serum and adipose tissue as well as the pro-inflammatory cytokines enhanced during a cycle of HF diet. These findings are significant because a milieu with altered adipokines in association with WC potentially aggravates the chronic inflammation attributed to dysregulated production and release of adipokines in mice.

  15. The Expression of Adipogenic Genes in Adipose Tissues of Feedlot Steers Fed Supplementary Palm Oil or Soybean Oil

    Directory of Open Access Journals (Sweden)

    Seong Ho Choi

    2016-03-01

    Full Text Available We hypothesized that supplementing finishing diets with palm oil would promote adipogenic gene expression and stearoyl-CoA desaturase (SCD gene expression in subcutaneous (s.c. and intramuscular (i.m. adipose tissues of feedlot steers. Eighteen Angus and Angus crossbred steers were assigned to three groups of 6 steers and fed a basal diet (control, with 3% palm oil, or with 3% soybean oil, for 70 d, top-dressed daily. Tailhead s.c. adipose tissue was obtained by biopsy at 14 d before the initiation of dietary treatments and at 35 d of dietary treatments. At slaughter, after 70 d of dietary treatment, tailhead s.c. adipose tissue and i.m. adipose tissue were obtained from the longissimus thoracis muscle. Palm oil increased plasma palmitic acid and soybean oil increased plasma linoleic acid and α-linolenic acid relative to the initial sampling time. Expression of AMP-activated protein kinase alpha (AMPKα and peroxisome proliferator-activated receptor gamma (PPARγ increased between the initial and intermediate biopsies and declined thereafter (p<0.03. SCD gene expression did not change between the initial and intermediate biopsies but declined by over 75% by the final period (p = 0.04, and G-coupled protein receptor 43 (GPR43 gene expression was unaffected by diet or time on trial. Soybean oil decreased (p = 0.01 PPARγ gene expression at the intermediate sample time. At the terminal sample time, PPARγ and SCD gene expression was less in i.m. adipose tissue than in s.c. adipose tissue (p<0.05. AMPKα gene expression was less in s.c. adipose tissue of palm oil-fed steers than in control steers (p = 0.04 and CCAAT enhancer binding protein-beta (CEBPβ gene expression was less in s.c. and i.m. adipose tissues of palm oil-fed steers than in soybean oil-fed steers (p<0.03. Soybean oil decreased SCD gene expression in s.c. adipose tissue (p = 0.05; SCD gene expression in palm oil-fed steers was intermediate between control and soybean oil-fed steers

  16. Deletion of CD1d in Adipocytes Aggravates Adipose Tissue Inflammation and Insulin Resistance in Obesity.

    Science.gov (United States)

    Huh, Jin Young; Park, Jeu; Kim, Jong In; Park, Yoon Jeong; Lee, Yun Kyung; Kim, Jae Bum

    2017-04-01

    Adipose tissue inflammation is an important factor in obesity that promotes insulin resistance. Among various cell types in adipose tissue, immune cells actively regulate inflammatory responses and affect whole-body energy metabolism. In particular, invariant natural killer T (iNKT) cells contribute to mitigating dysregulation of systemic energy homeostasis by counteracting obesity-induced inflammation in adipose tissue. However, the molecular mechanisms by which adipose iNKT cells become activated and mediate anti-inflammatory roles in obese adipose tissue have not been thoroughly understood yet. In the current study, we demonstrate that adipocyte CD1d plays a key role in the stimulation of adipose iNKT cells, leading to anti-inflammatory responses in high-fat diet (HFD)-fed mice. Accordingly, adipocyte-specific CD1d-knockout (CD1d(ADKO)) mice showed reduced numbers of iNKT cells in adipose tissues and decreased responses to α-galactosylceramide-induced iNKT cell activation. Additionally, HFD-fed CD1d(ADKO) mice revealed reduced interleukin-4 expression in adipose iNKT cells and aggravated adipose tissue inflammation and insulin resistance. Collectively, these data suggest that adipocytes could selectively stimulate adipose iNKT cells to mediate anti-inflammatory responses and attenuate excess proinflammatory responses in obese adipose tissue. © 2017 by the American Diabetes Association.

  17. Adipose tissue dysregulation and reduced insulin sensitivity in non-obese individuals with enlarged abdominal adipose cells

    National Research Council Canada - National Science Library

    Hammarstedt, Ann; Graham, Timothy E; Kahn, Barbara B

    2012-01-01

    Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver...

  18. Down-regulation of Zac1 gene expression in rat white adipose tissue by androgens.

    Science.gov (United States)

    Mirowska, Agnieszka; Sledzinski, Tomasz; Smolenski, Ryszard T; Swierczynski, Julian

    2014-03-01

    ZAC1 is a zinc-finger protein transcription factor, a transcriptional cofactor for nuclear receptors, and a co-activator of nuclear receptors, which interacts with multiple signaling pathways affecting apoptosis, cell cycle arrest, and metabolism. Some data suggest that ZAC1 regulates the expression of genes associated with function of adipose tissue. Since there is no information about the levels of Zac1 gene expression in white adipose tissue (WAT), and the expression of several genes associated with metabolic function of WAT is significantly lower in male than female animals, we have examined: (a) the relative ZAC1 mRNA levels in some organs/tissues, including three main depots of WAT, in 3-month-old male rats; (b) the relative ZAC1 mRNA levels in WAT of male and female rats; (c) the effect of orchidectomy and orchidectomy with concomitant testosterone treatment on ZAC1 mRNA and protein levels; (d) the effect of ovariectomy and ovariectomy with concomitant 17β-estradiol treatment on ZAC1 mRNA levels; (e) the effect of dihydrotestosterone on ZAC1 mRNA levels in isolated adipocytes. Our results indicate that: (a) ZAC1 mRNA levels are relatively high in WAT in comparison with other organs/tissues; (b) ZAC1 mRNA levels in subcutaneous WAT are approximately 2-fold lower than in epididymal and retroperitoneal adipose tissue; (c) ZAC1 mRNA levels in WAT of adult female rats are approximately 2-fold higher than in male rats; (d) testosterone is inversely related to ZAC1 mRNA and protein levels in WAT of male rats; and (e) dihydrotestosterone decreases the ZAC1 mRNA levels in adipocytes in dose dependent manner. In conclusion, Zac1 gene is highly expressed in white adipose tissue of adult rats. Androgens could play an important role in down-regulation of the ZAC1 mRNA and protein levels in rats.

  19. Isolation and expansion of adipose-derived stem cells for tissue engineering

    DEFF Research Database (Denmark)

    Fink, Trine; Rasmussen, Jeppe Grøndahl; Lund, Pia

    2011-01-01

    For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs for subseq......For treatment of cardiac failure with bone marrow-derived mesenchymal stem cells, several clinical trials are ongoing. However, more attention is gathering on the use of adipose tissue-derived stem cells (ASCs). This paper describes the optimization of isolation and propagation of ASCs...... and serum replacers were evaluated regarding their ability to support cell growth and preserve differentiation potential. Most of serum replacers proved inferior to fetal calf serum. Among the media tested, modified Eagle's media alpha was superior in promoting cell growth while preserving the ability...

  20. Two types of brown adipose tissue in humans.

    Science.gov (United States)

    Lidell, Martin E; Betz, Matthias J; Enerbäck, Sven

    2014-01-01

    During the last years the existence of metabolically active brown adipose tissue in adult humans has been widely accepted by the research community. Its unique ability to dissipate chemical energy stored in triglycerides as heat makes it an attractive target for new drugs against obesity and its related diseases. Hence the tissue is now subject to intense research, the hypothesis being that an expansion and/or activation of the tissue is associated with a healthy metabolic phenotype. Animal studies provide evidence for the existence of at least two types of brown adipocytes. Apart from the classical brown adipocyte that is found primarily in the interscapular region where it constitutes a thermogenic organ, a second type of brown adipocyte, the so-called beige adipocyte, can appear within white adipose tissue depots. The fact that the two cell types develop from different precursors suggests that they might be recruited and stimulated by different cues and therefore represent two distinct targets for therapeutic intervention. The aim of this commentary is to discuss recent work addressing the question whether also humans possess two types of brown adipocytes and to highlight some issues when looking for molecular markers for such cells.

  1. Regulation of insulin-stimulated glucose uptake in rat white adipose tissue upon chronic central leptin infusion: effects on adiposity.

    Science.gov (United States)

    Bonzón-Kulichenko, Elena; Fernández-Agulló, Teresa; Moltó, Eduardo; Serrano, Rosario; Fernández, Alejandro; Ros, Manuel; Carrascosa, José M; Arribas, Carmen; Martínez, Carmen; Andrés, Antonio; Gallardo, Nilda

    2011-04-01

    Leptin enhances the glucose utilization in most insulin target tissues and paradoxically decreases it in white adipose tissue (WAT), but knowledge of the mechanisms underlying the inhibitory effect of central leptin on the insulin-dependent glucose uptake in WAT is limited. After 7 d intracerebroventricular leptin treatment (0.2 μg/d) of rats, the overall insulin sensitivity and the responsiveness of WAT after acute in vivo insulin administration were analyzed. We also performed unilateral WAT denervation to clarify the role of the autonomic nervous system in leptin effects on the insulin-stimulated [(3)H]-2-deoxyglucose transport in WAT. Central leptin improved the overall insulin sensitivity but decreased the in vivo insulin action in WAT, including insulin receptor autophosphorylation, insulin receptor substrate-1 tyrosine-phosphorylation, and Akt activation. In this tissue, insulin receptor substrate-1 and glucose transporter 4 mRNA and protein levels were down-regulated after central leptin treatment. Additionally, a remarkable up-regulation of resistin, together with an augmented expression of suppressor of cytokine signaling 3 in WAT, was also observed in leptin-treated rats. As a result, the insulin-stimulated glucose transporter 4 insertion at the plasma membrane and the glucose uptake in WAT were impaired in leptin-treated rats. Finally, denervation of WAT abolished the inhibitory effect of central leptin on glucose transport and decreased suppressor of cytokine signaling 3 and resistin levels in this tissue, suggesting that resistin, in an autocrine/paracrine manner, might be a mediator of central leptin antagonism of insulin action in WAT. We conclude that central leptin, inhibiting the insulin-stimulated glucose uptake in WAT, may regulate glucose availability for triacylglyceride formation and accumulation in this tissue, thereby contributing to the control of adiposity.

  2. Adipose Tissue Dysregulation and Reduced Insulin Sensitivity in Non-Obese Individuals with Enlarged Abdominal Adipose Cells

    OpenAIRE

    Hammarstedt Ann; Graham Timothy E; Kahn Barbara B

    2012-01-01

    Abstract Background Obesity contributes to Type 2 diabetes by promoting systemic insulin resistance. Obesity causes features of metabolic dysfunction in the adipose tissue that may contribute to later impairments of insulin action in skeletal muscle and liver; these include reduced insulin-stimulated glucose transport, reduced expression of GLUT4, altered expression of adipokines, and adipocyte hypertrophy. Animal studies have shown that expansion of adipose tissue alone is not sufficient to ...

  3. Tissue/blood partition coefficients for xenon in various adipose tissue depots in man

    DEFF Research Database (Denmark)

    Bülow, J; Jelnes, Rolf; Astrup, A

    1987-01-01

    Tissue/blood partition coefficients (lambda) for xenon were calculated for subcutaneous adipose tissue from the abdominal wall and the thigh, and for the perirenal adipose tissue after chemical analysis of the tissues for lipid, water and protein content. The lambda in the perirenal tissue...... was found to correlate linearly to the relative body weight (RBW) in per cent with the regression equation lambda = 0.045 . RBW + 0.99. The subcutaneous lambda on the abdomen correlated linearly to the local skinfold thickness (SFT) with the equation lambda = 0.22 SFT + 2.99. Similarly lambda on the thigh...... correlated to SFT with the equation lambda = 0.20 . SFT + 4.63. It is concluded that the previously accepted lambda value of 10 is generally too high in perirenal as well as in subcutaneous tissue. Thus, by application of the present regression equations, it is possible to obtain more exact estimates...

  4. Age-Associated Increase in Cytokine Production During Systemic Inflammation-II: The Role of IL-1β in Age-Dependent IL-6 Upregulation in Adipose Tissue.

    Science.gov (United States)

    Starr, Marlene E; Saito, Mizuki; Evers, B Mark; Saito, Hiroshi

    2015-12-01

    Expression of interleukin-6 (IL-6) upon acute inflammatory stress is significantly augmented by aging in adipose tissue, a major source of this cytokine. In the present study, we examined the mechanism of age-dependent IL-6 overproduction using visceral white adipose tissue from C57BL/6 mice. Upon treatment with lipopolysaccharide (LPS) in vitro, IL-6 was produced by adipose tissue explants, and secreted levels were significantly higher in cultures from aged (24 months) mice compared to young (4 months). Interleukin 1 beta (IL-1β) and tumor necrosis factor alpha (TNFα), two inducers of IL-6, were mainly produced by the lungs and spleen rather than adipose tissue in mice after LPS injection. Treatment of adipose explants with physiological levels of IL-1β induced significant age-dependent secretion of IL-6, while treatment with TNFα had little effect, demonstrating an augmented response of adipose tissues to IL-1β in the aged. In vitro experiments utilizing a neutralizing antibody against IL-1β and in vivo experiments utilizing IL-1-receptor-1 deficient mice, confirmed that IL-6 overproduction in the aged is regulated by autocrine/paracrine action of IL-1β which specifically occurs in aged adipose tissues. These findings indicate an elevated inflammatory potential of adipose tissue in the aged and a unique IL-1β-mediated mechanism for IL-6 overproduction, which may impact age-associated vulnerability to acute inflammatory diseases such as sepsis.

  5. The Linkage between Breast Cancer, Hypoxia, and Adipose Tissue.

    Science.gov (United States)

    Rausch, Linda K; Netzer, Nikolaus C; Hoegel, Josef; Pramsohler, Stephan

    2017-01-01

    The development of breast cancer cells is linked to hypoxia. The hypoxia-induced factor HIF-1α influences metastasis through neovascularization. Hypoxia seems to decrease the responsiveness to hormonal treatment due to loss of estrogen receptors (ERs). Obesity is discussed to increase hypoxia in adipocytes, which promotes a favorable environment for tumor cells in mammary fat tissue, whereas, tumor cells profit from good oxygen supply and are influenced by its deprivation as target regions within tumors show. This review gives an overview of the current state on research of hypoxia and breast cancer in human adipose tissue. A systematic literature search was conducted on PubMed (2000-2016) by applying hypoxia and/or adipocytes and breast cancer as keywords. Review articles were excluded as well as languages other than English or German. There was no restriction regarding the study design or type of breast cancer. A total of 35 papers were found. Eight studies were excluded due to missing at least two of the three keywords. One paper was removed due to Russian language, and one was dismissed due to lack of adherence. Seven papers were identified as reviews. After applying exclusion criteria, 18 articles were eligible for inclusion. Two articles describe the impairment of mammary epithelial cell polarization through hypoxic preconditioning. A high amount of adipocytes enhances cancer progression due to the increased expression of HIF-1α which causes the loss of ER α protein as stated in four articles. Four articles analyzed that increased activation of HIF's induces a series of transcriptions resulting in tumor angiogenesis. HIF inhibition, especially when combined with cytotoxic chemotherapy, holds strong potential for tumor suppression as stated in further four articles. In two articles there is evidence of a strong connection between hypoxia, oxidative stress and a poor prognosis for breast cancer via HIF regulated pathways. Acute hypoxia seems to normalize the

  6. Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

    Science.gov (United States)

    Lancha, Andoni; Rodríguez, Amaia; Catalán, Victoria; Becerril, Sara; Sáinz, Neira; Ramírez, Beatriz; Burrell, María A; Salvador, Javier; Frühbeck, Gema; Gómez-Ambrosi, Javier

    2014-01-01

    Osteopontin (OPN) is a multifunctional extracellular matrix (ECM) protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD) using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT) and liver in wild type (WT) mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.

  7. Osteopontin deletion prevents the development of obesity and hepatic steatosis via impaired adipose tissue matrix remodeling and reduced inflammation and fibrosis in adipose tissue and liver in mice.

    Directory of Open Access Journals (Sweden)

    Andoni Lancha

    Full Text Available Osteopontin (OPN is a multifunctional extracellular matrix (ECM protein involved in multiple physiological processes. OPN expression is dramatically increased in visceral adipose tissue in obesity and the lack of OPN protects against the development of insulin resistance and inflammation in mice. We sought to unravel the potential mechanisms involved in the beneficial effects of the absence of OPN. We analyzed the effect of the lack of OPN in the development of obesity and hepatic steatosis induced by a high-fat diet (HFD using OPN-KO mice. OPN expression was upregulated in epididymal white adipose tissue (EWAT and liver in wild type (WT mice with HFD. OPN-KO mice had higher insulin sensitivity, lower body weight and fat mass with reduced adipose tissue ECM remodeling and reduced adipocyte size than WT mice under a HFD. Reduced MMP2 and MMP9 activity was involved in the decreased ECM remodeling. Crown-like structure number in EWAT as well as F4/80-positive cells and Emr1 expression in EWAT and liver increased with HFD, while OPN-deficiency blunted the increase. Moreover, our data show for the first time that OPN-KO under a HFD mice display reduced fibrosis in adipose tissue and liver, as well as reduced oxidative stress in adipose tissue. Gene expression of collagens Col1a1, Col6a1 and Col6a3 in EWAT and liver, as well as the profibrotic cytokine Tgfb1 in EWAT were increased with HFD, while OPN-deficiency prevented this increase. OPN deficiency prevented hepatic steatosis via reduction in the expression of molecules involved in the onset of fat accumulation such as Pparg, Srebf1, Fasn, Mogat1, Dgat2 and Cidec. Furthermore, OPN-KO mice exhibited higher body temperature and improved BAT function. The present data reveal novel mechanisms of OPN in the development of obesity, pointing out the inhibition of OPN as a promising target for the treatment of obesity and fatty liver.

  8. Angiopoietin Like Protein 2 (ANGPTL2) Promotes Adipose Tissue Macrophage and T lymphocyte Accumulation and Leads to Insulin Resistance

    Science.gov (United States)

    Sasaki, Yusuke; Ohta, Masayuki; Desai, Dhruv; Figueiredo, Jose-Luiz; Whelan, Mary C.; Sugano, Tomohiro; Yamabi, Masaki; Yano, Wataru; Faits, Tyler; Yabusaki, Katsumi; Zhang, Hengmin; Mlynarchik, Andrew K.; Inoue, Keisuke; Mizuno, Ken; Aikawa, Masanori

    2015-01-01

    Objectives Angiopoietin-like protein 2 (ANGPTL2), a recently identified pro-inflammatory cytokine, is mainly secreted from the adipose tissue. This study aimed to explore the role of ANGPTL2 in adipose tissue inflammation and macrophage activation in a mouse model of diabetes. Methodology/Principal Findings Adenovirus mediated lacZ (Ad-LacZ) or human ANGPTL2 (Ad-ANGPTL2) was delivered via tail vein in diabetic db/db mice. Ad-ANGPTL2 treatment for 2 weeks impaired both glucose tolerance and insulin sensitivity as compared to Ad-LacZ treatment. Ad-ANGPTL2 treatment significantly induced pro-inflammatory gene expression in white adipose tissue. We also isolated stromal vascular fraction from epididymal fat pad and analyzed adipose tissue macrophage and T lymphocyte populations by flow cytometry. Ad-ANGPTL2 treated mice had more adipose tissue macrophages (F4/80+CD11b+) and a larger M1 macrophage subpopulation (F4/80+CD11b+CD11c+). Moreover, Ad-ANGPTL2 treatment increased a CD8-positive T cell population in adipose tissue, which preceded increased macrophage accumulation. Consistent with our in vivo results, recombinant human ANGPTL2 protein treatment increased mRNA levels of pro-inflammatory gene products and production of TNF-α protein in the human macrophage-like cell line THP-1. Furthermore, Ad-ANGPTL2 treatment induced lipid accumulation and increased fatty acid synthesis, lipid metabolism related gene expression in mouse liver. Conclusion ANGPTL2 treatment promotes macrophage accumulation and activation. These results suggest potential mechanisms for insulin resistance. PMID:26132105

  9. Adipose tissue and adipocytes support tumorigenesis and metastasis.

    Science.gov (United States)

    Nieman, Kristin M; Romero, Iris L; Van Houten, Bennett; Lengyel, Ernst

    2013-10-01

    Adipose tissue influences tumor development in two major ways. First, obese individuals have a higher risk of developing certain cancers (endometrial, esophageal, and renal cell cancer). However, the risk of developing other cancers (melanoma, rectal, and ovarian) is not altered by body mass. In obesity, hypertrophied adipose tissue depots are characterized by a state of low grade inflammation. In this activated state, adipocytes and inflammatory cells secrete adipokines and cytokines which are known to promote tumor development. In addition, the adipocyte mediated conversion of androgens to estrogen specifically contributes to the development of endometrial cancer, which shows the greatest relative risk (6.3-fold) increase between lean and obese individuals. Second, many tumor types (gastric, breast, colon, renal, and ovarian) grow in the anatomical vicinity of adipose tissue. During their interaction with cancer cells, adipocytes dedifferentiate into pre-adipocytes or are reprogrammed into cancer-associated adipocytes (CAA). CAA secrete adipokines which stimulate the adhesion, migration, and invasion of tumor cells. Cancer cells and CAA also engage in a dynamic exchange of metabolites. Specifically, CAA release fatty acids through lipolysis which are then transferred to cancer cells and used for energy production through β-oxidation. The abundant availability of lipids from adipocytes in the tumor microenvironment, supports tumor progression and uncontrolled growth. Given that adipocytes are a major source of adipokines and energy for the cancer cell, understanding the mechanisms of metabolic symbiosis between cancer cells and adipocytes, should reveal new therapeutic possibilities. This article is part of a Special Issue entitled Lipid Metabolism in Cancer. Copyright © 2013 Elsevier B.V. All rights reserved.

  10. Organochlorine pesticide levels in female adipose tissue from Puebla, Mexico.

    Science.gov (United States)

    Waliszewski, Stefan M; Sanchez, K; Caba, M; Saldariaga-Noreña, H; Meza, E; Zepeda, R; Valencia Quintana, R; Infanzon, R

    2012-02-01

    The objective of this study was to determine the levels of organochlorine pesticides HCB, α-β-γ-HCH, pp'DDE, op'DDT and pp'DDT in adipose tissue of females living in Puebla, Mexico. Organochlorine pesticides were analyzed in 75 abdominal adipose tissue samples taken during 2010 by autopsy at the Forensic Services of Puebla. The results were expressed as mg/kg on fat basis. In analyzed samples the following pesticides were detected: p,p'-DDE in 100% of samples at mean 1.464 mg/kg; p,p'-DDT in 96.0.% of samples at mean 0.105 mg/kg; op'DDT in 89.3% of monitored samples at mean 0.025 mg/kg and β-HCH in 94.7% of the samples at mean 0.108 mg/kg. To show if organochlorine pesticide levels in monitored female's adipose tissues are age dependant, the group was divided in three ages ranges (13-26, 26-57 and 57-96 years). The mean and median levels of all organochlorine pesticides increase significantly (p 0.05). The present results compared to previous ones from 2008 indicates an increase in the concentrations during the 2010 study, but only the differences for pp'DDE and op'DDT were statistically significant. The 2010 group of females was older compared to the 2008 group. The presence of organochlorine pesticide residues is still observed, indicating uniform and permanent exposure to the pesticides by Puebla inhabitants.

  11. Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain.

    Directory of Open Access Journals (Sweden)

    Marcella K Vaicik

    Full Text Available Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4-/- and compared to wild-type (Lama4+/+ control animals. Lama4-/- mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.

  12. Laminin α4 deficient mice exhibit decreased capacity for adipose tissue expansion and weight gain.

    Science.gov (United States)

    Vaicik, Marcella K; Thyboll Kortesmaa, Jill; Movérare-Skrtic, Sofia; Kortesmaa, Jarkko; Soininen, Raija; Bergström, Göran; Ohlsson, Claes; Chong, Li Yen; Rozell, Björn; Emont, Margo; Cohen, Ronald N; Brey, Eric M; Tryggvason, Karl

    2014-01-01

    Obesity is a global epidemic that contributes to the increasing medical burdens related to type 2 diabetes, cardiovascular disease and cancer. A better understanding of the mechanisms regulating adipose tissue expansion could lead to therapeutics that eliminate or reduce obesity-associated morbidity and mortality. The extracellular matrix (ECM) has been shown to regulate the development and function of numerous tissues and organs. However, there is little understanding of its function in adipose tissue. In this manuscript we describe the role of laminin α4, a specialized ECM protein surrounding adipocytes, on weight gain and adipose tissue function. Adipose tissue accumulation, lipogenesis, and structure were examined in mice with a null mutation of the laminin α4 gene (Lama4-/-) and compared to wild-type (Lama4+/+) control animals. Lama4-/- mice exhibited reduced weight gain in response to both age and high fat diet. Interestingly, the mice had decreased adipose tissue mass and altered lipogenesis in a depot-specific manner. In particular, epididymal adipose tissue mass was specifically decreased in knock-out mice, and there was also a defect in lipogenesis in this depot as well. In contrast, no such differences were observed in subcutaneous adipose tissue at 14 weeks. The results suggest that laminin α4 influences adipose tissue structure and function in a depot-specific manner. Alterations in laminin composition offers insight into the roll the ECM potentially plays in modulating cellular behavior in adipose tissue expansion.

  13. Tracking of autologous adipose tissue-derived mesenchymal stromal cells with in vivo magnetic resonance imaging and histology after intralesional treatment of artificial equine tendon lesions : A pilot study

    NARCIS (Netherlands)

    Geburek, Florian; Mundle, Kathrin; Conrad, Sabine; Hellige, Maren; Walliser, Ulrich; van Schie, Hans T M; van Weeren, René; Skutella, Thomas; Stadler, Peter M

    2016-01-01

    BACKGROUND: Adipose tissue-derived mesenchymal stromal cells (AT-MSCs) are frequently used to treat equine tendinopathies. Up to now, knowledge about the fate of autologous AT-MSCs after intralesional injection into equine superficial digital flexor tendons (SDFTs) is very limited. The purpose of th

  14. Is Crohn’s creeping fat an adipose tissue?

    OpenAIRE

    Olivier, Isabelle; Theodorou, Vassilia; Valet, Philippe; Castan-Laurell, Isabelle; Guillou, Hervé; Bertrand-Michel, Justine; Cartier, Christel; Bezirard, Valerie; Ducroc, Robert; Segain, Jean-Pierre; Portier, Guillaume; Kirzin, Sylvain; Moreau, Jacques; Duffas, Jean-Pierre; Ferrier, Laurent

    2011-01-01

    Background: In human pathology, the ‘‘creeping fat’’ (CF) ofthe mesentery is unique to Crohn’s disease (CD). CF is usuallyreferred to as an ectopic extension of mesenteric adipose tissue(MAT). However, since no animal model developing CF has everbeen established, very little is known about this type of fat-depotexpansion and its role in the development of the disease.Methods: We developed and standardized an experimental protocolin mice that reproducibly induces CF development when asevere co...

  15. Adipose Tissue-Derived Stem Cells for Myocardial Regeneration

    Science.gov (United States)

    Joo, Hyung Joon; Kim, Jong-Ho

    2017-01-01

    Over the past decade, stem cell therapy has been extensively studied for clinical application for heart diseases. Among various stem cells, adipose tissue-derived stem cell (ADSC) is still an attractive stem cell resource due to its abundance and easy accessibility. In vitro studies showed the multipotent differentiation potentials of ADSC, even differentiation into cardiomyocytes. Many pre-clinical animal studies have also demonstrated promising therapeutic results of ADSC. Furthermore, there were several clinical trials showing the positive results in acute myocardial infarction using ADSC. The present article covers the brief introduction, the suggested therapeutic mechanisms, application methods including cell dose and delivery, and human clinical trials of ADSC for myocardial regeneration.

  16. Metabolic Dysregulation and Adipose Tissue Fibrosis: Role of Collagen VI▿ †

    OpenAIRE

    Khan, Tayeba; Muise, Eric S.; Iyengar, Puneeth; Wang, Zhao V.; Chandalia, Manisha; Abate, Nicola; Zhang, Bei B.; Bonaldo, Paolo; Chua, Streamson; Scherer, Philipp E.

    2008-01-01

    Adipocytes are embedded in a unique extracellular matrix whose main function is to provide mechanical support, in addition to participating in a variety of signaling events. During adipose tissue expansion, the extracellular matrix requires remodeling to accommodate adipocyte growth. Here, we demonstrate a general upregulation of several extracellular matrix components in adipose tissue in the diabetic state, therefore implicating “adipose tissue fibrosis” as a hallmark of metabolically chall...

  17. Role of bioactive lipid mediators in obese adipose tissue inflammation and endocrine dysfunction.

    OpenAIRE

    Lopategi, Aritz; López-Vicario, Cristina; Alcaraz-Quiles, José; García-Alonso, Verónica; Rius, Bibiana; Titos Rodríguez, Esther; Clària i Enrich, Joan

    2015-01-01

    White adipose tissue is recognized as an active endocrine organ implicated in the maintenance of metabolic homeostasis. However, adipose tissue function, which has a crucial role in the development of obesity-related comorbidities including insulin resistance and non-alcoholic fatty liver disease, is dysregulated in obese individuals. This review explores the physiological functions and molecular actions of bioactive lipids biosynthesized in adipose tissue including sphingolipids and phosphol...

  18. Decreased adipose tissue zinc content is associated with metabolic parameters in high fat fed Wistar rats

    OpenAIRE

    Alexey A. Tinkov; Elizaveta V. Popova; Evgenia R. Gatiatulina; Anastasia A. Skalnaya; Elena N. Yakovenko; Irina B. Alchinova; Mikhail Y. Karganov; Anatoly V. Skalny; Nikonorov, Alexandr A.

    2016-01-01

    Background. Limited data on adipose tissue zinc content in obesity exist. At the same time, the association between adipose tissue zinc content and metabolic parameters in dietary-induced obesity is poorly studied. Therefore, the primary objective of this study is to assess adipose tissue zinc content and its association  with morphometric parameters, adipokine spectrum, proinflammatory cytokines, and apolipoprotein profile in high fat fed Wistar rats. Material and method...

  19. Observations on Preadipocytes and Their Distribution Patterns in Rat Adipose Tissue

    Science.gov (United States)

    1981-01-01

    enzyme lipoprotein lipase (Hietanen and viously (Stiles et al., 󈨏) in rat adipose tissue Greenwood, 󈨑). Exercise training initiated and suggest that...Huston, C.G. Plopper, and A.L. Hecker increased hormone sensitivity during in vitro adipocyte (1975) Adipose tissue cellularity and lipolysis : Response to... adipose tissue developing into adipocytes. J. Usuku, G., K. Iyama, and K. Ohzono (1978) Ultrastructural Lipid Res., 19: 316-324. studies on the white

  20. Hypoxia in adipose tissue: a basis for the dysregulation of tissue function in obesity?

    Science.gov (United States)

    Trayhurn, Paul; Wang, Bohan; Wood, I Stuart

    2008-08-01

    White adipose tissue is a key endocrine and secretory organ, releasing multiple adipokines, many of which are linked to inflammation and immunity. During the expansion of adipose tissue mass in obesity there is a major inflammatory response in the tissue with increased expression and release of inflammation-related adipokines, including IL-6, leptin, monocyte chemoattractant protein-1 and TNF-alpha, together with decreased adiponectin production. We proposed in 2004 (Trayhurn & Wood, Br J Nutr 92, 347-355) that inflammation in adipose tissue in obesity is a response to hypoxia in enlarged adipocytes distant from the vasculature. Hypoxia has now been directly demonstrated in adipose tissue of several obese mouse models (ob/ob, KKAy, diet-induced) and molecular studies indicate that the level of the hypoxia-inducible transcription factor, hypoxia-inducible factor-1 alpha, is increased, as is expression of the hypoxia-sensitive marker gene, GLUT1. Cell- culture studies on murine and human adipocytes show that hypoxia (induced by low O2 or chemically) leads to stimulation of the expression and secretion of a number of inflammation-related adipokines, including angiopoietin-like protein 4, IL-6, leptin, macrophage migration inhibitory factor and vascular endothelial growth factor. Hypoxia also stimulates the inflammatory response of macrophages and inhibits adipocyte differentiation from preadipocytes. GLUT1 gene expression, protein level and glucose transport by human adipocytes are markedly increased by hypoxia, indicating that low O2 tension stimulates glucose utilisation. It is suggested that hypoxia has a pervasive effect on adipocyte metabolism and on overall adipose tissue function, underpinning the inflammatory response in the tissue in obesity and the subsequent development of obesity-associated diseases, particularly type 2 diabetes and the metabolic syndrome.

  1. The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

    NARCIS (Netherlands)

    van Dongen, Joris A.; Stevens, Hieronymus P.; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C.

    2016-01-01

    Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be obt

  2. A chromatin immunoprecipitation (ChIP) protocol for use in whole human adipose tissue.

    Science.gov (United States)

    Haim, Yulia; Tarnovscki, Tanya; Bashari, Dana; Rudich, Assaf

    2013-11-01

    Chromatin immunoprecipitation (ChIP) has become a central method when studying in vivo protein-DNA interactions, with the major challenge being the hope to capture "authentic" interactions. While ChIP protocols have been optimized for use with specific cell types and tissues including adipose tissue-derived cells, a working ChIP protocol addressing the challenges imposed by fresh whole human adipose tissue has not been described. Utilizing human paired omental and subcutaneous adipose tissue obtained during elective abdominal surgeries, we have carefully identified and optimized individual steps in the ChIP protocol employed directly on fresh tissue fragments. We describe a complete working protocol for using ChIP on whole adipose tissue fragments. Specific steps required adaptation of the ChIP protocol to human whole adipose tissue. In particular, a cross-linking step was performed directly on fresh small tissue fragments. Nuclei were isolated before releasing chromatin, allowing better management of fat content; a sonication protocol to obtain fragmented chromatin was optimized. We also demonstrate the high sensitivity of immunoprecipitated chromatin from adipose tissue to freezing. In conclusion, we describe the development of a ChIP protocol optimized for use in studying whole human adipose tissue, providing solutions for the unique challenges imposed by this tissue. Unraveling protein-DNA interaction in whole human adipose tissue will likely contribute to elucidating molecular pathways contributing to common human diseases such as obesity and type 2 diabetes.

  3. The Secretory Function of Adipocytes in the Physiology of White Adipose Tissue

    NARCIS (Netherlands)

    Wang, P.; Mariman, E.; Renes, J.; Keijer, J.

    2008-01-01

    White adipose tissue, previously regarded as a passive lipid storage site, is now viewed as a dynamic tissue. It has the capacity to actively communicate by sending and receiving different types of signals. An overview of these signals, the external modulators that affect adipose tissue and the secr

  4. The Fractionation of Adipose Tissue (FAT) procedure to obtain stromal vascular fractions for regenerative purposes

    NARCIS (Netherlands)

    van Dongen, Joris A; Stevens, Hieronymus P; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C

    2016-01-01

    Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be obt

  5. The fractionation of adipose tissue procedure to obtain stromal vascular fractions for regenerative purposes

    NARCIS (Netherlands)

    van Dongen, Joris A.; Stevens, Hieronymus P.; Parvizi, Mojtaba; van der Lei, Berend; Harmsen, Martin C.

    2016-01-01

    Autologous adipose tissue transplantation is clinically used to reduce dermal scarring and to restore volume loss. The therapeutic benefit on tissue damage more likely depends on the stromal vascular fraction of adipose tissue than on the adipocyte fraction. This stromal vascular fraction can be obt

  6. TUSC5 regulates insulin-mediated adipose tissue glucose uptake by modulation of GLUT4 recycling

    Directory of Open Access Journals (Sweden)

    Nigel Beaton

    2015-11-01

    Conclusions: Collectively, these findings establish TUSC5 as an adipose tissue-specific protein that enables proper protein recycling, linking the ubiquitous vesicle traffic machinery with tissue-specific insulin-mediated glucose uptake into adipose tissue and the maintenance of a healthy metabolic phenotype in mice and humans.

  7. Modal response of a computational vocal fold model with a substrate layer of adipose tissue.

    Science.gov (United States)

    Jones, Cameron L; Achuthan, Ajit; Erath, Byron D

    2015-02-01

    This study demonstrates the effect of a substrate layer of adipose tissue on the modal response of the vocal folds, and hence, on the mechanics of voice production. Modal analysis is performed on the vocal fold structure with a lateral layer of adipose tissue. A finite element model is employed, and the first six mode shapes and modal frequencies are studied. The results show significant changes in modal frequencies and substantial variation in mode shapes depending on the strain rate of the adipose tissue. These findings highlight the importance of considering adipose tissue in computational vocal fold modeling.

  8. Adrenergic regulation of cellular plasticity in brown, beige/brite and white adipose tissues.

    Science.gov (United States)

    Ramseyer, Vanesa D; Granneman, James G

    2016-01-01

    The discovery of brown adipose tissue in adult humans along with the recognition of adipocyte heterogeneity and plasticity of white fat depots has renewed the interest in targeting adipose tissue for therapeutic benefit. Adrenergic activation is a well-established means of recruiting catabolic adipocyte phenotypes in brown and white adipose tissues. In this article, we review mechanisms of brown adipocyte recruitment by the sympathetic nervous system and by direct β-adrenergic receptor activation. We highlight the distinct modes of brown adipocyte recruitment in brown, beige/brite, and white adipose tissues, UCP1-independent thermogenesis, and potential non-thermogenic, metabolically beneficial effects of brown adipocytes.

  9. Prolactin suppresses malonyl-CoA concentration in human adipose tissue

    DEFF Research Database (Denmark)

    Nilsson, L. A.; Roepstorff, Carsten; Kiens, Bente

    2009-01-01

    +/-6% compared to control 100+/-5% (p=0.022) in cultured human adipose tissue. In addition, prolactin was found to decrease glucose transporter 4 ( GLUT4) mRNA expression, which may cause decreased glucose uptake. In conclusion, we propose that prolactin decreases lipogenesis in human adipose tissue...... as a consequence of suppressed malonyl-CoA concentration in parallel with decreased GLUT-4 expression. In the lactating woman, this regulation in adipose tissue may enhance the provision of nutrients for the infant instead of nutrients being stored in adipose tissue. In hyperprolactinemic individuals, a suppressed...

  10. Sugar-sweetened and diet beverages in relation to visceral adipose tissue.

    Science.gov (United States)

    Odegaard, Andrew O; Choh, Audrey C; Czerwinski, Stefan A; Towne, Bradford; Demerath, Ellen W

    2012-03-01

    Frequent sugar-sweetened beverage (SSB) intake has been consistently associated with increased adiposity and cardio-metabolic risk, whereas the association with diet beverages is more mixed. We examined how these beverages associate with regional abdominal adiposity measures, specifically visceral adipose tissue (VAT). In a cross-sectional analysis of 791 non-Hispanic white men and women aged 18-70 we examined how beverage consumption habits obtained from a food frequency questionnaire associate with overall and abdominal adiposity measures from MRI. With increasing frequency of SSB intake, we observed increases in waist circumference (WC) and the proportion of visceral to subcutaneous abdominal adipose tissue (VAT%), with no change in total body fat (TBF%) or BMI. Greater frequency of diet beverage intake was associated with greater WC, BMI, and TBF%, but was not associated with variation in visceral adiposity We conclude that increased frequency of SSB consumption is associated with a more adverse abdominal adipose tissue deposition pattern.

  11. M1-M2 balancing act in white adipose tissue browning - a new role for RIP140.

    Science.gov (United States)

    Liu, Pu-Ste; Lin, Yi-Wei; Burton, Frank H; Wei, Li-Na

    2015-01-01

    A "Holy Grail" sought in medical treatment of obesity is to be able to biologically reprogram their adipose tissues to burn fat rather than store it. White adipose tissue (WAT) stores fuel and its expansion underlines insulin resistance (IR) whereas brown adipose tissue (BAT) burns fuel and stimulates insulin sensitivity. These two types of fats seesaw within our bodies via a regulatory mechanism that involves intricate communication between adipocytes and blood cells, particularly macrophages that migrate into adipose deposits. The coregulator, Receptor Interacting Protein 140 (RIP140), plays a key role in regulating this communication. In mice on a high-fat diet, the level of RIP140 in macrophages is dramatically elevated to activate their inflammatory M1 polarization and enhance their recruitment into WAT, facilitating IR. Conversely, lowering the level of RIP140 in macrophages not only reduces M1 macrophages but also expands alternatively polarized, anti-inflammatory M2 macrophages, triggering white adipose tissue browning, fat burning, and restoration of insulin sensitivity. This suggests a potential therapeutic strategy for reversing IR, obesity, and atherosclerotic or even cosmetic fat deposits: therapeutic browning of white adipose deposits by diminishing RIP140 levels in macrophages.

  12. Skeletal Muscle Derived IL-6 in Liver and Adipose Tissue Metabolism

    DEFF Research Database (Denmark)

    Knudsen, Jakob Grunnet

    Summary Physical activity can lead to metabolic disease and treatment of several metabolic diseases include exercise training. Skeletal muscle has, due to its central role in glucose and fat metabolism at rest and during exercise been studied in detail with regard to exercise training. The role...... and adipose tissue metabolism is unknown. It has been suggested that myokines, such as IL-6, released from skeletal muscle affects liver and adipose tissue and are involved in the regulation of exercise training adaptations. Thus, the aim of this thesis was to investigate the role of skeletal muscle derived...... indicate that during 1h of exercise the liver utilizes carbohydrates for oxidation rather than gluconeogenesis and that gluconeogenic activity during 1h of exercise is not regulated through increases in protein content. The aim of study III was to investigate the role of skeletal muscle derived IL-6...

  13. The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue

    DEFF Research Database (Denmark)

    Lynes, Matthew D; Leiria, Luiz O; Lundh, Morten

    2017-01-01

    . Mechanistically, 12,13-diHOME increased fatty acid (FA) uptake into brown adipocytes by promoting the translocation of the FA transporters FATP1 and CD36 to the cell membrane. These data suggest that 12,13-diHOME, or a functional analog, could be developed as a treatment for metabolic disorders.......Brown adipose tissue (BAT) and beige adipose tissue combust fuels for heat production in adult humans, and so constitute an appealing target for the treatment of metabolic disorders such as obesity, diabetes and hyperlipidemia. Cold exposure can enhance energy expenditure by activating BAT...

  14. Phthalate is associated with insulin resistance in adipose tissue of male rat: role of antioxidant vitamins.

    Science.gov (United States)

    Rajesh, Parsanathan; Sathish, Sampath; Srinivasan, Chinnapaiyan; Selvaraj, Jayaraman; Balasubramanian, Karundevi

    2013-03-01

    Diethyl hexyl phthalate (DEHP) is a plasticizer, commonly used in a variety of products, including lubricants, perfumes, hairsprays and cosmetics, construction materials, wood finishers, adhesives, floorings and paints. DEHP is an endocrine disruptor and it has a continuum of influence on various organ systems in human beings and experimental animals. However, specific effects of DEHP on insulin signaling in adipose tissue are not known. Adult male albino rats of Wistar strain were divided into four groups. Control, DEHP treated (dissolved in olive oil at a dose of 10, and 100 mg/kg body weight, respectively, once daily through gastric intubations for 30 days) and DEHP + vitamin E (50 mg/kg body weight) and C (100 mg/kg body weight) dissolved in olive oil and distilled water, respectively, once daily through gastric intubations for 30 days. After the completion of treatment, adipose tissue was dissected out to assess various parameters. DEHP treatment escalated H(2)O(2) and hydroxyl radical levels as well as lipid peroxidation in the adipose tissue. DEHP impaired the expression of insulin signaling molecules and their phosphorelay pathways leading to diminish plasma membrane GLUT4 level and thus decreased glucose uptake and oxidation. Blood glucose level was elevated as a result of these changes. Supplementation of vitamins (C & E) prevented the DEHP-induced changes. It is concluded that DEHP-induced ROS and lipid peroxidation disrupts the insulin signal transduction in adipose tissue and favors glucose intolerance. Antioxidant vitamins have a protective role against the adverse effect of DEHP. Copyright © 2012 Wiley Periodicals, Inc.

  15. Endurance training changes in lipolytic responsiveness of obese adipose tissue.

    Science.gov (United States)

    De Glisezinski, I; Crampes, F; Harant, I; Berlan, M; Hejnova, J; Langin, D; Rivière, D; Stich, V

    1998-12-01

    The aim of this study was to investigate the effect of aerobic exercise training on the lipolytic response of adipose tissue in obese subjects. Thirteen men (body mass index = 36.9 +/- 1.3 kg/m2) were submitted to aerobic physical training on a cycloergometer (30-45 min, 4 days a wk) for 3 mo. Adipocyte sensitivity to the action of catecholamines and insulin was studied in vitro before and after training. Training induced a decrease in the percentage of fat mass (P < 0.05) without changing the body weight. Basal lipolysis and hormone-sensitive lipase activity were significantly decreased after training (P < 0.05). The lipolytic effects of epinephrine, isoprenaline (beta-adrenoceptor agonist), and dobutamine (beta1-adrenoceptor agonist) were significantly increased (P < 0.05) but not those of procaterol (beta2-adrenoceptor agonist). The antilipolytic effects of alpha2-adrenoceptor and insulin were significantly decreased (P < 0.05). Lipolysis stimulation by agents acting at the postreceptor level was unchanged after training. In conclusion, aerobic physical training in obese male subjects modifies adipose tissue lipolysis through an enhancement of beta-adrenergic response and a concomitant blunting of adipocyte antilipolytic activity.

  16. Adipose Tissue-Derived Stem Cells in Regenerative Medicine.

    Science.gov (United States)

    Frese, Laura; Dijkman, Petra E; Hoerstrup, Simon P

    2016-07-01

    In regenerative medicine, adult stem cells are the most promising cell types for cell-based therapies. As a new source for multipotent stem cells, human adipose tissue has been introduced. These so called adipose tissue-derived stem cells (ADSCs) are considered to be ideal for application in regenerative therapies. Their main advantage over mesenchymal stem cells derived from other sources, e.g. from bone marrow, is that they can be easily and repeatable harvested using minimally invasive techniques with low morbidity. ADSCs are multipotent and can differentiate into various cell types of the tri-germ lineages, including e.g. osteocytes, adipocytes, neural cells, vascular endothelial cells, cardiomyocytes, pancreatic β-cells, and hepatocytes. Interestingly, ADSCs are characterized by immunosuppressive properties and low immunogenicity. Their secretion of trophic factors enforces the therapeutic and regenerative outcome in a wide range of applications. Taken together, these particular attributes of ADSCs make them highly relevant for clinical applications. Consequently, the therapeutic potential of ADSCs is enormous. Therefore, this review will provide a brief overview of the possible therapeutic applications of ADSCs with regard to their differentiation potential into the tri-germ lineages. Moreover, the relevant advancements made in the field, regulatory aspects as well as other challenges and obstacles will be highlighted.

  17. Characterization of mesenchymal stem cells derived from equine adipose tissue

    Directory of Open Access Journals (Sweden)

    A.M. Carvalho

    2013-08-01

    Full Text Available Stem cell therapy has shown promising results in tendinitis and osteoarthritis in equine medicine. The purpose of this work was to characterize the adipose-derived mesenchymal stem cells (AdMSCs in horses through (1 the assessment of the capacity of progenitor cells to perform adipogenic, osteogenic and chondrogenic differentiation; and (2 flow cytometry analysis using the stemness related markers: CD44, CD90, CD105 and MHC Class II. Five mixed-breed horses, aged 2-4 years-old were used to collect adipose tissue from the base of the tail. After isolation and culture of AdMSCs, immunophenotypic characterization was performed through flow cytometry. There was a high expression of CD44, CD90 and CD105, and no expression of MHC Class II markers. The tri-lineage differentiation was confirmed by specific staining: adipogenic (Oil Red O, osteogenic (Alizarin Red, and chondrogenic (Alcian Blue. The equine AdMSCs are a promising type of adult progenitor cell for tissue engineering in veterinary medicine.

  18. Organotypic culture of human bone marrow adipose tissue.

    Science.gov (United States)

    Uchihashi, Kazuyoshi; Aoki, Shigehisa; Shigematsu, Masamori; Kamochi, Noriyuki; Sonoda, Emiko; Soejima, Hidenobu; Fukudome, Kenji; Sugihara, Hajime; Hotokebuchi, Takao; Toda, Shuji

    2010-04-01

    The precise role of bone marrow adipose tissue (BMAT) in the marrow remains unknown. The purpose of the present study was therefore to describe a novel method for studying BMAT using 3-D collagen gel culture of BMAT fragments, immunohistochemistry, ELISA and real-time reverse transcription-polymerase chain reaction. Mature adipocytes and CD45+ leukocytes were retained for >3 weeks. Bone marrow stromal cells (BMSC) including a small number of lipid-laden preadipocytes and CD44+/CD105+ mesenchymal stem cell (MSC)-like cells, developed from BMAT. Dexamethasone (10 micromol/L), but not insulin (20 mU/mL), significantly increased the number of preadipocytes. Dexamethasone and insulin also promoted leptin production and gene expression in BMAT. Adiponectin production by BMAT was BMAT, in which adiponectin protein secretion is normally very low, and that BMAT may exhibit a different phenotype from that of the visceral and subcutaneous adipose tissues. BMAT-osteoblast interactions were also examined, and it was found that osteoblasts inhibited the development of BMSC and reduced leptin production, while BMAT inhibited the growth and differentiation of osteoblasts. The present novel method proved to be useful for the study of BMAT biology.

  19. [Regulations of berberine on gene expression of BMP4 transcriptional pathways to improve visceral white adipose tissues insulin resistance in type 2 diabetic hamsters].

    Science.gov (United States)

    Li, Guo-Sheng; Liu, Xu-Han; Li, Xin-Yu; Gao, Zheng-Nan; Huang, Lan; Liu, Ya-Li

    2016-02-01

    To study the effects of berberine on the gene mRNA expressions of BMP4 transcriptional pathways and brown/white adipose tissue conversion transcriptional pathways in visceral white adipose tissues(VWAT) in type 2 diabetic hamsters and explore the relevant mechanisms. The obese insulin-resistant hamster model were induced by using high-fat diet, and then the type 2 diabetic hamster model was created through injection with low-dose streptozotocin in the obese insulin-resistant hamster model. After the modeling, the hamsters were randomly divided into normal control, obese insulin-resistant, type 2 diabetic and berberine-treated diabetic groups. After the nine-week treatment, real-time quantitative PCR was used to measure the changes in gene mRNA expressions of VWAT BMP4 transcriptional pathways, brown/white adipose tissue conversion transcriptional pathways and their target genes in different groups. The results showed that the gene mRNA expressions of BMP4, BMPRⅡ, BMPRlA, Smad1, Smad5, Smad8, p38/MAPK, ATF2, PRDM16, C/EBPβ, PGC1α, PPARγ and brown adipose tissue-specific genes was decreased and that of Smad6, Smurf1 and white adipose tissue-specific genes was increased in VWAT of model hamsters. Treatment with berberine regulated BMP4 transcriptional pathways and brown adipose tissue transcriptional pathways and induced the gene mRNA expression of brown adipose tissue-specific genes in VWAT to develop browning gene phenotype of white adipose tissues, and then improved fat-induced insulin resistance. These findings indicated that BMP4 transcriptional pathways involved in the formation of fat-induced visceral white adipose tissues insulin resistance (FIVWATIR) and the browning molecular mechanism of white adipose tissues induced by berberine. Copyright© by the Chinese Pharmaceutical Association.

  20. Differential regulation of oxytocin receptor in various adipose tissue depots and skeletal muscle types in obese Zucker rats.

    Science.gov (United States)

    Gajdosechova, L; Krskova, K; Olszanecki, R; Zorad, S

    2015-07-01

    Multifunctional peptide oxytocin currently undergoes intensive research due to its proposed anti-obesity properties. Until now, little is known about regulation of oxytocin receptor in metabolically active tissues in obesity. The aim of the present study was to measure expression of oxytocin receptor upon obese phenotype with respect to the variety among adipose tissue and skeletal muscles with distinct anatomical localisation. Total homogenates were prepared from epididymal, retroperitoneal and inguinal adipose tissues as well as quadriceps and soleus muscle from lean and obese Zucker rats. Oxytocin receptor protein was determined by immunoblot. Interestingly, elevated oxytocin receptor was observed in epididymal adipose tissue of obese rats in contrast to its downregulation in subcutaneous and no change in retroperitoneal fat. In lean animals, oxytocin receptor protein was expressed at similar levels in all adipose depots. This uniformity was not observed in the case of skeletal muscle in which fibre type composition seems to be determinant of oxytocin receptor expression. Quadriceps muscle with the predominance of glycolytic fibres exhibits higher oxytocin receptor expression than almost exclusively oxidative soleus muscle. Oxytocin receptor protein levels were decreased in both skeletal muscles analysed upon obese phenotype. The present work demonstrates that even under identical endocrine circumstances, oxytocin receptor is differentially regulated in adipose tissue of obese rats depending on fat depot localisation. These results also imply which tissues may be preferentially targeted by oxytocin treatment in metabolic disease.

  1. Fatty acids do not pay the toll: effect of SFA and PUFA on human adipose tissue and mature adipocytes inflammation

    Directory of Open Access Journals (Sweden)

    Murumalla Ravi Kumar

    2012-12-01

    Full Text Available Abstract Background On the basis that high fat diet induces inflammation in adipose tissue, we wanted to test the effect of dietary saturated and polysunsaturated fatty acids on human adipose tissue and adipocytes inflammation. Moreover we wanted to determine if TLR2 and TLR4 are involved in this pathway. Methods Human adipose tissue and adipocytes primary cultures were treated with endotoxin-free BSA conjugated with SFA (lauric acid and palmitic acid - LA and PA and PUFA (eicosapentaeneic acid, docosahexaenoic acid and oleic acid - EPA, DHA and OA with or without LPS. Cytokines were then assayed by ELISA (TNF-alpha, IL-6 and MCP-1. In order to determine if TLR2 and TLR4 are activated by fatty acid (FA, we used HEK-Blue cells transfected by genes from TLR2 or TLR4 pathways associated with secreted alkaline phosphatase reporter gene. Results None of the FA tested in HEK-Blue cells were able to activate TLR2 or TLR4, which is concordant with the fact that after FA treatment, adipose tissue and adipocytes cytokines levels remain the same as controls. However, all the PUFA tested: DHA, EPA and to a lesser extent OA down-regulated TNF-alpha, IL-6 and MCP-1 secretion in human adipose tissue and adipocytes cultures. Conclusions This study first confirms that FA do not activate TLR2 and TLR4. Moreover by using endotoxin-free BSA, both SFA and PUFA tested were not proinflammatory in human adipose tissue and adipocytes model. More interestingly we showed that some PUFA exert an anti-inflammatory action in human adipose tissue and adipocytes model. These results are important since they clarify the relationship between dietary fatty acids and inflammation linked to obesity.

  2. The effect of exercise on visceral adipose tissue in overweight adults: a systematic review and meta-analysis.

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    Dirk Vissers

    Full Text Available Excessive visceral adipose tissue appears to trigger a cascade of metabolic disturbances that seem to coexist with ectopic fat storage in muscle, liver, heart and the ß-cell. Therefore, the reduction of visceral adipose tissue potentially plays a pivotal role in the treatment of the metabolic syndrome. The purpose of this systematic review and meta-analysis is to describe the overall effect of exercise on visceral adipose tissue and to provide an overview of the effect of different exercise regimes, without caloric restriction, on visceral adipose tissue in obese persons. A systematic literature search was performed according to the PRISMA statement for reporting systematic reviews and meta-analyses. The initial search resulted in 87 articles after removing duplicates. After screening on title, abstract and full-text 15 articles (totalling 852 subjects fulfilled the a priori inclusion criteria. The quality of each eligible study was assessed in duplicate with "The Critical Review Form for Quantitative Studies". Using random-effects weights, the standardized mean difference (Hedge's g of the change in visceral adipose tissue was -0.497 with a 95% confidence interval of -0.655 to -0.340. The Z-value was -6.183 and the p-value (two tailed was <0.001. A subgroup analysis was performed based on gender, type of training and intensity. Aerobic training of moderate or high intensity has the highest potential to reduce visceral adipose tissue in overweight males and females. These results suggest that an aerobic exercise program, without hypocaloric diet, can show beneficial effects to reduce visceral adipose tissue with more than 30 cm(2 (on CT analysis in women and more than 40 cm(2 in men, even after 12 weeks.

  3. Remodeling of adipose tissue at experimental diabetes mellitus

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    O. A. Konovalova

    2013-08-01

    Full Text Available Introduction Diabetes mellitus (DM type 1 is chronіc disease whith progressive selective destruction of β- cells pancreatic islets (of Langerhans and whith development of absolute insulin failure. Active immune mechanisms take part in pathogenesis of this disease. Recently many publication appeared which report about the role of adipose tissue. In such way adipose tissue is not only the main metabolic regulator and endocrine organ synthesizing more than 30 regulatory proteins- adipokines, but it is one of the organs of immune system. Dysregulation of adipose tissue leads to morphological restructuring- remodeling of adipocytes, and the development of inflammation of adipose tissue in its turn is integral component of progression of many diseases. The aim of research The aim of this study was to investigate the morphological and functional state of parapancreatic fibre adipocytes in male Wistar rats in experimental diabetes mellitus. Materials and methods The study has been carried out on 20 male Wistar rats with weight 115-135 g. The animals were divided into 2 groups. The control group, which were injected 0,5 ml 0,1 М citrate buffer intraperitoneally (1group. Rats with 7 day experimental streptozotocin-induced diabetes mellitus were in the 2nd group. Adipose tissue was examined on the seventh day. For histological examination sections were colored with haematoxylin and eosin. Images were taken by using a fluorescence microscope PrimoStar(ZEISS,Germany with a computer-assisted video system AxioCam 5c (ZEISS,Germany including the NIH-Image software (NIH Image version 1·46. All statistical analyses were performed using EXCEL MS Office 2010 (Microsoft Corp., USA, STATISTICA 6.0 (Stat-Soft, 2001 software. Results were expressed as mean values ± SEM. Differences were considered statistically significant if the p value was <0.05. Results Injection of streptozotocin to experimental animals led to the development of experimental diabetes mellitus

  4. Dietary conjugated linoleic acids decrease leptin in porcine adipose tissue.

    Science.gov (United States)

    Di Giancamillo, Alessia; Rossi, Raffaella; Vitari, Francesca; Pastorelli, Grazia; Corino, Carlo; Domeneghini, Cinzia

    2009-10-01

    We investigated the effects of dietary conjugated linoleic acids (CLA) on white adipose tissue (WAT) in heavy pigs. Twelve pigs were assigned to 1 of 2 groups supplemented with either 0 or 0.75% of a CLA preparation (isomeric mixture) and were slaughtered at 159 +/- 2.3 kg live weight. Their subcutaneous WAT was analyzed by both chemical and microanatomical methods. The WAT of CLA-fed pigs tended to have a higher protein content (P = 0.064) and smaller adipocytes (P = 0.053) than that of control (CTR) pigs. The number of proliferating preadipocytes tended to be greater (P = 0.076) in pigs fed CLA, whereas the number of apoptotic adipocytes was greater (P leptin (Ob) expression was lower (P = 0.048) in adipocytes from treated pigs and Western blot quantification of Ob revealed lower levels (P tissue.

  5. Controlled cellular energy conversion in brown adipose tissue thermogenesis

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    Horowitz, J. M.; Plant, R. E.

    1978-01-01

    Brown adipose tissue serves as a model system for nonshivering thermogenesis (NST) since a) it has as a primary physiological function the conversion of chemical energy to heat; and b) preliminary data from other tissues involved in NST (e.g., muscle) indicate that parallel mechanisms may be involved. Now that biochemical pathways have been proposed for brown fat thermogenesis, cellular models consistent with a thermodynamic representation can be formulated. Stated concisely, the thermogenic mechanism in a brown fat cell can be considered as an energy converter involving a sequence of cellular events controlled by signals over the autonomic nervous system. A thermodynamic description for NST is developed in terms of a nonisothermal system under steady-state conditions using network thermodynamics. Pathways simulated include mitochondrial ATP synthesis, a Na+/K+ membrane pump, and ionic diffusion through the adipocyte membrane.

  6. Intramuscular Adipose Tissue, Sarcopenia, and Mobility Function in Older Individuals

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    Robin L. Marcus

    2012-01-01

    Full Text Available Objective. Intramuscular adipose tissue (IMAT and sarcopenia may adversely impact mobility function and physical activity. This study determined the association of locomotor muscle structure and function with mobility function in older adults. Method. 109 older adults with a variety of comorbid disease conditions were examined for thigh muscle composition via MRI, knee extensor strength via isometric dynamometry, and mobility function. The contribution of strength, quadriceps lean tissue, and IMAT to explaining the variability in mobility function was examined using multivariate linear regression models. Results. The predictors as a group contributed 27–45% of the variance in all outcome measures; however, IMAT contributed between 8–15% of the variance in all four mobility variables, while lean explained only 5% variance in only one mobility measure. Conclusions. Thigh IMAT, a newly identified muscle impairment appears to be a potent muscle variable related to the ability of older adults to move about in their community.

  7. Global gene expression profiling of brown to white adipose tissue transformation in sheep reveals novel transcriptional components linked to adipose remodeling

    DEFF Research Database (Denmark)

    Basse, Astrid L.; Dixen, Karen; Yadav, Rachita

    2015-01-01

    Background: Large mammals are capable of thermoregulation shortly after birth due to the presence of brown adipose tissue (BAT). The majority of BAT disappears after birth and is replaced by white adipose tissue (WAT). Results: We analyzed the postnatal transformation of adipose in sheep....... Conclusions: Using global gene expression profiling of the postnatal BAT to WAT transformation in sheep, we provide novel insight into adipose tissue plasticity in a large mammal, including identification of novel transcriptional components linked to adipose tissue remodeling. Moreover, our data set provides...

  8. Visceral adipose tissue: emerging role of gluco- and mineralocorticoid hormones in the setting of cardiometabolic alterations

    Science.gov (United States)

    Boscaro, Marco; Giacchetti, Gilberta; Ronconi, Vanessa

    2012-01-01

    Several clinical and experimental lines of evidence have highlighted the detrimental effects of visceral adipose tissue excess on cardiometabolic parameters. Besides, recent findings have shown the effects of gluco-and mineralocorticoid hormones on adipose tissue and have also underscored the interplay existing between such adrenal steroids and their respective receptors in the modulation of adipose tissue biology. While the fundamental role played by glucocorticoids on adipocyte differentiation and storage was already well known, the relevance of the mineralocorticoids in the physiology of the adipose organ is of recent acquisition. The local and systemic renin–angiotensin–aldosterone system (RAAS) acting on adipose tissue seems to contribute to the development of the cardiometabolic phenotype so that its modulation can have deep impact on human health. A better understanding of the pathophysiology of the adipose organ is of crucial importance in order to identify possible therapeutic approaches that can avoid the development of such cardiovascular and metabolic sequelae. PMID:22804097

  9. Adipose tissue-targeted 11β-hydroxysteroid dehydrogenase type 1 inhibitor protects against diet-induced obesity.

    Science.gov (United States)

    Liu, Juan; Wang, Long; Zhang, Aisen; Di, Wenjuan; Zhang, Xiao; Wu, Lin; Yu, Jing; Zha, Juanmin; Lv, Shan; Cheng, Peng; Hu, Miao; Li, Yujie; Qi, Hanmei; Ding, Guoxian; Zhong, Yi

    2011-01-01

    Current pharmacological treatments for obesity and metabolic syndrome have various limitations. Recently, adipose tissue 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1) has been proposed as a novel therapeutic target for the treatment of obesity and metabolic syndrome. Nevertheless, there is no adipose tissue-targeted 11β-HSD1 inhibitor available now. We sought to develop a new 11β-HSD1 pharmacological inhibitor that homes specifically to the white adipose tissue and aimed to investigate whether adipose tissue-targeted 11β-HSD1 inhibitor might decrease body weight gain and improve glucose tolerance in diet-induced obesity mice. BVT.2733, an 11β-HSD1 selective inhibitor was connected with a peptide CKGGRAKDC that homes to white fat vasculature. CKGGRAKDC-BVT.2733 (T-BVT) or an equimolar mixture of CKGGRAKDC and BVT.2733 (NT-BVT) was given to diet-induced obesity mice for two weeks through subcutaneous injection. T-BVT decreased body weight gain, improved glucose tolerance and decreased adipocyte size compared with vehicle treated mice. In adipose tissue T-BVT administration significantly increased adiponectin, vaspin mRNA levels; In liver T-BVT administration decreased the mRNA level of phosphoenolpyruvate carboxykinase (PEPCK), increased the mRNA levels of mitochondrial carnitine palmi-toyltransferase-I (mCPT-I) and peroxisome proliferator-activated receptorα(PPARα). No significant differences in adipocyte size and hepatic gene expression were observed after treatment with NT-BVT compared with vehicle treated mice, though NT-BVT also decreased body weight gain, improved glucose tolerance, and increased uncoupling protein-2 (UCP-2) mRNA levels in muscle. These results suggest that an adipose tissue-targeted pharmacological inhibitor of 11β-HSD1 may prove to be a new approach for the treatment of obesity and metabolic syndrome.

  10. Hedgehog signalling in myeloid cells impacts on body weight, adipose tissue inflammation and glucose metabolism.

    Science.gov (United States)

    Braune, Julia; Weyer, Ulrike; Matz-Soja, Madlen; Hobusch, Constance; Kern, Matthias; Kunath, Anne; Klöting, Nora; Kralisch, Susann; Blüher, Matthias; Gebhardt, Rolf; Zavros, Yana; Bechmann, Ingo; Gericke, Martin

    2017-05-01

    Recently, hedgehog (Hh) was identified as a crucial player in adipose tissue development and energy expenditure. Therefore, we tested whether Hh ligands are regulated in obesity. Further, we aimed at identifying potential target cells of Hh signalling and studied the functional impact of Hh signalling on adipose tissue inflammation and glucose metabolism. Hh ligands and receptors were analysed in adipose tissue or serum from lean and obese mice as well as in humans. To study the impact on adipose tissue inflammation and glucose metabolism, Hh signalling was specifically blocked in myeloid cells using a conditional knockout approach (Lys-Smo (-/-)). Desert Hh (DHH) and Indian Hh (IHH) are local Hh ligands, whereas Sonic Hh is not expressed in adipose tissue from mice or humans. In mice, obesity leads to a preferential upregulation of Hh ligands (Dhh) and signalling components (Ptch1, Smo and Gli1) in subcutaneous adipose tissue. Further, adipose tissue macrophages are Hh target cells owing to the expression of Hh receptors, such as Patched1 and 2. Conditional knockout of Smo (which encodes Smoothened, a mandatory Hh signalling component) in myeloid cells increases body weight and adipose tissue inflammation and attenuates glucose tolerance, suggesting an anti-inflammatory effect of Hh signalling. In humans, adipose tissue expression of DHH and serum IHH decrease with obesity and type 2 diabetes, which might be explained by the intake of metformin. Interestingly, metformin reduced Dhh and Ihh expression in mouse adipose tissue explants. Hh signalling in myeloid cells affects adipose tissue inflammation and glucose metabolism and may be a potential target to treat type 2 diabetes.

  11. Brown adipose tissue: a potential target in the fight against obesity and the metabolic syndrome.

    Science.gov (United States)

    Poekes, Laurence; Lanthier, Nicolas; Leclercq, Isabelle A

    2015-12-01

    BAT (brown adipose tissue) is the main site of thermogenesis in mammals. It is essential to ensure thermoregulation in newborns. It is also found in (some) adult humans. Its capacity to oxidize fatty acids and glucose without ATP production contributes to energy expenditure and glucose homoeostasis. Brown fat activation has thus emerged as an attractive therapeutic target for the treatment of obesity and the metabolic syndrome. In the present review, we integrate the recent advances on the metabolic role of BAT and its relation with other tissues as well as its potential contribution to fighting obesity and the metabolic syndrome. © 2015 Authors; published by Portland Press Limited.

  12. Lipid Profiling of In Vitro Cell Models of Adipogenic Differentiation: Relationships With Mouse Adipose Tissues.

    Science.gov (United States)

    Liaw, Lucy; Prudovsky, Igor; Koza, Robert A; Anunciado-Koza, Rea V; Siviski, Matthew E; Lindner, Volkhard; Friesel, Robert E; Rosen, Clifford J; Baker, Paul R S; Simons, Brigitte; Vary, Calvin P H

    2016-09-01

    Our objective was to characterize lipid profiles in cell models of adipocyte differentiation in comparison to mouse adipose tissues in vivo. A novel lipid extraction strategy was combined with global lipid profiling using direct infusion and sequential precursor ion fragmentation, termed MS/MS(ALL) . Perirenal and inguinal white adipose tissue and interscapular brown adipose tissues from adult C57BL/6J mice were analyzed. 3T3-L1 preadipocytes, ear mesenchymal progenitor cells, and brown adipose-derived BAT-C1 cells were also characterized. Over 3000 unique lipid species were quantified. Principal component analysis showed that perirenal versus inguinal white adipose tissues varied in lipid composition of triacyl- and diacylglycerols, sphingomyelins, glycerophospholipids and, notably, cardiolipin CL 72:3. In contrast, hexosylceramides and sphingomyelins distinguished brown from white adipose. Adipocyte differentiation models showed broad differences in lipid composition among themselves, upon adipogenic differentiation, and with adipose tissues. Palmitoyl triacylglycerides predominate in 3T3-L1 differentiation models, whereas cardiolipin CL 72:1 and SM 45:4 were abundant in brown adipose-derived cell differentiation models, respectively. MS/MS(ALL) data suggest new lipid biomarkers for tissue-specific lipid contributions to adipogenesis, thus providing a foundation for using in vitro models of adipogenesis to reflect potential changes in adipose tissues in vivo. J. Cell. Biochem. 117: 2182-2193, 2016. © 2016 Wiley Periodicals, Inc.

  13. Telmisartan attenuates the inflamed mesenteric adipose tissue in spontaneous colitis by mechanisms involving regulation of neurotensin/microRNA-155 pathway.

    Science.gov (United States)

    Li, Yi; Zuo, Lugen; Zhu, Weiming; Gong, Jianfeng; Zhang, Wei; Guo, Zhen; Gu, Lili; Li, Ning; Li, Jieshou

    2015-02-15

    Mesenteric adipose tissue hypertrophy is unique to Crohn's disease while the molecular basis of the crosstalk between MAT and the intestinal inflammation is largely unknown. Telmisartan is an angiotensin II type 1 receptor blocker and a peroxisome proliferator-activated receptor-receptor-γ agonist which has beneficial effects on fat distribution and pro-inflammatory adipokine expression. We evaluated the effect of telmisartan upon mesenteric adipose tissue alterations and inflammatory features in IL-10(-)/(-) mice. We found that treatment with telmisartan significantly ameliorated the severity of colitis in IL-10(-)/(-) mice. Additionally, administration of telmisartan was associated with restoration of mesenteric adipose tissue adipocyte morphology and the expression of adipokines. Furthermore, telmisartan treatment suppressed the neurotensin/microRNA-155 pathway in mesenteric adipose tissue from spontaneous colitis which was confirmed by an in vitro study using cultured mesenteric adipose tissue from Crohn's disease patients. Administration of telmisartan showed promising results in spontaneous colitis which was associated with the attenuated mesenteric adipose tissue alteration which at least in part, was associated with its activity in the regulation of the neurotensin/microRNA-155 pathway. These results support the hypothesis that regulating the abnormal immune response in adipose tissue is an important target for the treatment of Crohn's disease. Copyright © 2015 Elsevier Inc. All rights reserved.

  14. Androgen effects on adipose tissue architecture and function in nonhuman primates.

    Science.gov (United States)

    Varlamov, Oleg; White, Ashley E; Carroll, Julie M; Bethea, Cynthia L; Reddy, Arubala; Slayden, Ov; O'Rourke, Robert W; Roberts, Charles T

    2012-07-01

    The differential association of hypoandrogenism in men and hyperandrogenism in women with insulin resistance and obesity suggests that androgens may exert sex-specific effects on adipose and other tissues, although the underlying mechanisms remain poorly understood. Moreover, recent studies also suggest that rodents and humans may respond differently to androgen imbalance. To achieve better insight into clinically relevant sex-specific mechanisms of androgen action, we used nonhuman primates to investigate the direct effects of gonadectomy and hormone replacement on white adipose tissue. We also employed a novel ex vivo approach that provides a convenient framework for understanding of adipose tissue physiology under a controlled tissue culture environment. In vivo androgen deprivation of males did not result in