scholarly journals Inhibition of Sam68 triggers adipose tissue browning

2015 ◽  
Vol 225 (3) ◽  
pp. 181-189 ◽  
Author(s):  
Junlan Zhou ◽  
Min Cheng ◽  
Chan Boriboun ◽  
Mariam M Ardehali ◽  
Changfei Jiang ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Acid Oxidation ◽  
M2 Macrophage ◽  
Fat Depots ◽  
Reduced Body ◽  
Brown Adipose ◽  
The Difference

Obesity is associated with insulin resistance and type 2 diabetes; molecular mechanisms that promote energy expenditure can be utilized for effective therapy. Src-associated in mitosis of 68 kDa (Sam68) is potentially significant, because knockout (KO) of Sam68 leads to markedly reduced adiposity. In the present study, we sought to determine the mechanism by which Sam68 regulates adiposity and energy homeostasis. We first found that Sam68 KO mice have a significantly reduced body weight as compared to controls, and the difference is explained entirely by decreased adiposity. Interestingly, these effects were not mediated by a difference in food intake; rather, they were associated with enhanced physical activity. When they were fed a high-fat diet, Sam68 KO mice gained much less body weight and fat mass than their WT littermates did, and they displayed an improved glucose and insulin tolerance. In Sam68 KO mice, the brown adipose tissue (BAT), inguinal, and epididymal depots were smaller, and their adipocytes were less hypertrophied as compared to their WT littermates. The BAT of Sam68 KO mice exhibited reduced lipid stores and expressed higher levels of Ucp1 and key thermogenic and fatty acid oxidation genes. Similarly, depots of inguinal and epididymal white adipose tissue (WAT) in Sam68 KO mice appeared browner, their multilocular Ucp1-positive cells were much more abundant, and the expression of Ucp1, Cidea, Prdm16, and Ppargc1a genes was greater as compared to WT controls, which suggests that the loss of Sam68 also promotes WAT browning. Furthermore, in all of the fat depots of the Sam68 KO mice, the expression of M2 macrophage markers was up-regulated, and that of M1 markers was down-regulated. Thus, Sam68 plays a crucial role in controlling thermogenesis and may be targeted to combat obesity and associated disorders.

scholarly journals DSS-induced colitis is associated with adipose tissue dysfunction and disrupted hepatic lipid metabolism leading to hepatosteatosis and dyslipidemia in mice

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Jeonghyeon Kwon ◽  
Chungho Lee ◽  
Sungbaek Heo ◽  
Bobae Kim ◽  
Chang-Kee Hyun
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Activity Index ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Acid Oxidation ◽  
Barrier Dysfunction ◽  
Alcoholic Fatty Liver ◽  
Brown Adipose

AbstractConsidering high prevalence of non-alcoholic fatty liver diseases (NAFLD) in patients with inflammatory bowel disease (IBD), this study aimed to elucidate molecular mechanisms for how intestinal inflammatory conditions are causally linked to hepatic steatosis and dyslipidemia. Both younger and older mice treated with acute or chronic dextran sodium sulfate (DSS) developed colitis, which was evidenced by weight loss, colon length shortening, and elevated disease activity index and inflammation score. They also showed decreased expression of intestinal barrier function-related proteins and elevated plasma lipopolysaccharide level, indicating DSS-induced barrier dysfunction and thereby increased permeability. Interestingly, they displayed phenotypes of hepatic fat accumulation and abnormal blood lipid profiles. This DSS-induced colitis-associated lipid metabolic dysfunction was due to overall disruption of metabolic processes including fatty acid oxidation, lipogenesis, lipolysis, reverse cholesterol transport, bile acid synthesis, and white adipose tissue browning and brown adipose tissue thermogenesis, most of which are mediated by key regulators of energy homeostasis such as FGF21, adiponectin, and irisin, via SIRT1/PGC-1α- and LXRα-dependent pathways. Our study suggests a potential molecular mechanism underlying the comorbidity of NAFLD and IBD, which could provide a key to understanding how the two diseases are pathogenically linked and discovering critical therapeutic targets for their treatment.

scholarly journals A Lipophilic Fucoxanthin-Rich Phaeodactylum tricornutum Extract Ameliorates Effects of Diet-Induced Obesity in C57BL/6J Mice

Nutrients ◽  
2019 ◽  
Vol 11 (4) ◽  
pp. 796 ◽  
Author(s):  
Andrea Gille ◽  
Bojan Stojnic ◽  
Felix Derwenskus ◽  
Andreas Trautmann ◽  
Ulrike Schmid-Staiger ◽  
...  
Keyword(s):  
Gene Expression ◽  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Phaeodactylum Tricornutum ◽  
Body Weight Gain ◽  
Acid Oxidation ◽  
Lipid Uptake ◽  
Interscapular Brown Adipose Tissue ◽  
Brown Adipose

Phaeodactylum tricornutum (P. tricornutum) comprise several lipophilic constituents with proposed anti-obesity and anti-diabetic properties. We investigated the effect of an ethanolic P. tricornutum extract (PTE) on energy metabolism in obesity-prone mice fed a high fat diet (HFD). Six- to eight-week-old male C57BL/6J mice were switched to HFD and, at the same time, received orally placebo or PTE (100 mg or 300 mg/kg body weight/day). Body weight, body composition, and food intake were monitored. After 26 days, blood and tissue samples were collected for biochemical, morphological, and gene expression analyses. PTE-supplemented mice accumulated fucoxanthin metabolites in adipose tissues and attained lower body weight gain, body fat content, weight of white adipose tissue (WAT) depots, and inguinal WAT adipocyte size than controls, independent of decreased food intake. PTE supplementation was associated with lower expression of Mest (a marker of fat tissue expandability) in WAT depots, lower gene expression related to lipid uptake and turnover in visceral WAT, increased expression of genes key to fatty acid oxidation and thermogenesis (Cpt1, Ucp1) in subcutaneous WAT, and signs of thermogenic activation including enhanced UCP1 protein in interscapular brown adipose tissue. In conclusion, these data show the potential of PTE to ameliorate HFD-induced obesity in vivo.

scholarly journals Energy homeostasis in apolipoprotein AIV and cholecystokinin-deficient mice

2017 ◽  
Vol 313 (5) ◽  
pp. R535-R548 ◽  
Author(s):  
Jonathan Weng ◽  
Danwen Lou ◽  
Stephen C. Benoit ◽  
Natalie Coschigano ◽  
Stephen C. Woods ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
Fat Mass ◽  
High Fat Diet ◽  
Energy Homeostasis ◽  
Lipid Transport ◽  
Fat Absorption ◽  
High Fat ◽  
Reduced Body ◽  
Brown Adipose

Apolipoprotein AIV (ApoAIV) and cholecystokinin (CCK) are well-known satiating signals that are stimulated by fat consumption. Peripheral ApoAIV and CCK interact to prolong satiating signals. In the present study, we hypothesized that ApoAIV and CCK control energy homeostasis in response to high-fat diet feeding. To test this hypothesis, energy homeostasis in ApoAIV and CCK double knockout (ApoAIV/CCK-KO), ApoAIV knockout (ApoAIV-KO), and CCK knockout (CCK-KO) mice were monitored. When animals were maintained on a low-fat diet, ApoAIV/CCK-KO, ApoAIV-KO, and CCK-KO mice had comparable energy intake and expenditure, body weight, fat mass, fat absorption, and plasma parameters relative to the controls. In contrast, these KO mice exhibited impaired lipid transport to epididymal fat pads in response to intraduodenal infusion of dietary lipids. Furthermore, ApoAIV-KO mice had upregulated levels of CCK receptor 2 (CCK2R) in the small intestine while ApoAIV/CCK-KO mice had upregulated levels of CCK2R in the brown adipose tissue. After 20 wk of a high-fat diet, ApoAIV-KO and CCK-KO mice had comparable body weight and fat mass, as well as lower energy expenditure at some time points. However, ApoAIV/CCK-KO mice exhibited reduced body weight and adiposity relative to wild-type mice, despite having normal food intake. Furthermore, ApoAIV/CCK-KO mice displayed normal fat absorption and locomotor activity, as well as enhanced energy expenditure. These observations suggest that mice lacking ApoAIV and CCK have reduced body weight and adiposity, possibly due to impaired lipid transport and elevated energy expenditure.

scholarly journals Epigenetic Regulators of White Adipocyte Browning

Epigenomes ◽  
2021 ◽  
Vol 5 (1) ◽  
pp. 3
Author(s):  
Ravikanth Nanduri
Keyword(s):  
Adipose Tissue ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
White Adipocyte ◽  
Primary Function ◽  
Obesity And Diabetes ◽  
Brown Adipose ◽  
Beige Adipocytes ◽  
Epigenetic Regulators

Adipocytes play an essential role in maintaining energy homeostasis in mammals. The primary function of white adipose tissue (WAT) is to store energy; for brown adipose tissue (BAT), primary function is to release fats in the form of heat. Dysfunctional or excess WAT can induce metabolic disorders such as dyslipidemia, obesity, and diabetes. Preadipocytes or adipocytes from WAT possess sufficient plasticity as they can transdifferentiate into brown-like beige adipocytes. Studies in both humans and rodents showed that brown and beige adipocytes could improve metabolic health and protect from metabolic disorders. Brown fat requires activation via exposure to cold or β-adrenergic receptor (β-AR) agonists to protect from hypothermia. Considering the fact that the usage of β-AR agonists is still in question with their associated side effects, selective induction of WAT browning is therapeutically important instead of activating of BAT. Hence, a better understanding of the molecular mechanisms governing white adipocyte browning is vital. At the same time, it is also essential to understand the factors that define white adipocyte identity and inhibit white adipocyte browning. This literature review is a comprehensive and focused update on the epigenetic regulators crucial for differentiation and browning of white adipocytes.

In Vivo Plasminogen Deficiency Reduces Fat Accumulation

2002 ◽  
Vol 87 (06) ◽  
pp. 1011-1019 ◽  
Author(s):  
Jill Ellis ◽  
Lawrence Yuen ◽  
Jane Hoover-Plow
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Stromal Cells ◽  
Whole Body ◽  
Glycerol Phosphate ◽  
Tissue Accumulation ◽  
Fat Depots ◽  
Reduced Body ◽  
Reduced Rate

SummaryObesity and non-insulin dependent diabetes are associated with a decrease in fibrinolysis, which is mediated by the plasminogen system. The purpose of the current study was to investigate the role of the plasminogen system in the reduced body weight of the plasminogen deficient (Plg−/−) mice. In this study we have found that the reduced body weight in Plg−/− mice is due to a reduced rate of the adipose tissue (25% less) and whole body fat (30% less) accumulation during growth in Plg−/− compared to wild-type (WT) littermates. When the mice are fed a high fat-lipogenic diet, adipose tissue accumulation increases in the Plg−/− mice indicating that the capacity for lipid filling of cells was not blocked. In addition, glycerol phosphate dehydrogenase, a marker of late differentiation, was not different in the depots from WT and Plg−/− mice. The number of stromal cells (number × 105/g adipose tissue), isolated from inguinal (Plg−/− 3.4 ± 1.2, n = 6; WT 0.17 ± 0.07, n = 7, p < 0.02) and gonadal (Plg−/− 11.0 ± 0.4, n = 6; WT 3.1 ± 0.7, n = 7, p < 0.05) fat depots, was markedly higher in the depots from the Plg−/− mice than WT mice. Differentiation of stromal cells in culture from the Plg−/− mice was reduced compared to cells from WT mice. These results suggest that differences in the stromal cell population are responsible for the reduced adipose tissue accumulation in the Plg−/− mice, and that the plasminogen system plays an important role in adipose tissue accumulation.

scholarly journals Corticotropin-Releasing Hormone-Mediated Pathway of Leptin to Regulate Feeding, Adiposity, and Uncoupling Protein Expression in Mice

Endocrinology ◽  
2003 ◽  
Vol 144 (8) ◽  
pp. 3547-3554 ◽  
Author(s):  
Takayuki Masaki ◽  
Go Yoshimichi ◽  
Seiichi Chiba ◽  
Tohru Yasuda ◽  
Hitoshi Noguchi ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Food Intake ◽  
Mrna Expression ◽  
White Adipose Tissue ◽  
Energy Homeostasis ◽  
Uncoupling Protein ◽  
Hypothalamic Nucleus ◽  
Fat Cell ◽  
Brown Adipose

Abstract To examine the functional role of CRH in the regulation of energy homeostasis by leptin, we measured the effects of the CRH antagonist, α-helical CRH 8–41 (αCRH) on a number of factors affected by leptin activity. These included food intake, body weight, hypothalamic c-fos-like immunoreactivity (c-FLI), weight and histological characterization of white adipose tissue, and mRNA expressions of uncoupling protein (UCP) in brown adipose tissue (BAT) in C57Bl/6 mice. Central infusion of leptin into the lateral cerebroventricle (icv) caused significant induction of c-FLI in the paraventricular nucleus (PVN), ventromedial hypothalamic nucleus (VMH), dorsomedial hypothalamic nucleus, and arcuate nucleus. In all these nuclei, the effect of leptin on expression of cFLI in the PVN and VMH was decreased by treatment with αCRH. Administration of leptin markedly decreased cumulative food intake and body weight with this effect being attenuated by pretreatment with αCRH. In peripheral tissue, leptin up-regulated BAT UCP1 mRNA expression and reduced fat depositions in this tissue. Those changes in BAT were also decreased by treatment with αCRH. As a consequence of the effects on food intake or energy expenditure, treatment with αCRH attenuated the leptin-induced reduction of body adiposity, fat cell size, triglyceride contents, and ob mRNA expression in white adipose tissue. Taken together, these results indicate that CRH neurons in the PVN and VMH may be an important mediator for leptin that contribute to regulation of feeding, adiposity, and UCP expression.

scholarly journals Persistent low body weight in humans is associated with higher mitochondrial activity in white adipose tissue

2019 ◽  
Vol 110 (3) ◽  
pp. 605-616 ◽  
Author(s):  
Yiin Ling ◽  
Jérôme Carayol ◽  
Bogdan Galusca ◽  
Carles Canto ◽  
Christophe Montaurier ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Differentially Expressed Genes ◽  
White Adipose Tissue ◽  
Molecular Mechanisms ◽  
Differentially Expressed ◽  
Molecular Signature ◽  
Acid Oxidation ◽  
Mitochondrial Activity

ABSTRACT Background Constitutional thinness (CT) is a state of low but stable body weight (BMI ≤18 kg/m2). CT subjects have normal-range hormonal profiles and food intake but exhibit resistance to weight gain despite living in the modern world's obesogenic environment. Objective The goal of this study is to identify molecular mechanisms underlying this protective phenotype against weight gain. Methods We conducted a clinical overfeeding study on 30 CT subjects and 30 controls (BMI 20–25 kg/m2) matched for age and sex. We performed clinical and integrative molecular and transcriptomic analyses on white adipose and muscle tissues. Results Our results demonstrate that adipocytes were markedly smaller in CT individuals (mean ± SEM: 2174 ± 142 μm 2) compared with controls (3586 ± 216 μm2) (P < 0.01). The mitochondrial respiratory capacity was higher in CT adipose tissue, particularly at the level of complex II of the electron transport chain (2.2-fold increase; P < 0.01). This higher activity was paralleled by an increase in mitochondrial number (CT compared with control: 784 ± 27 compared with 675 ± 30 mitochondrial DNA molecules per cell; P < 0.05). No evidence for uncoupled respiration or “browning” of the white adipose tissue was found. In accordance with the mitochondrial differences, CT subjects had a distinct adipose transcriptomic profile [62 differentially expressed genes (false discovery rate of 0.1 and log fold change >0.75)], with many differentially expressed genes associating with positive metabolic outcomes. Pathway analyses revealed an increase in fatty acid oxidation ( P = 3 × 10−04) but also triglyceride biosynthesis (P = 3.6 × 10−04). No differential response to the overfeeding was observed in the 2 groups. Conclusions The distinct molecular signature of the adipose tissue in CT individuals suggests the presence of augm ented futile lipid cycling, rather than mitochondrial uncoupling, as a way to increase energy expenditure in CT individuals. We propose that increased mitochondrial function in adipose tissue is an important mediator in sustaining the low body weight in CT individuals. This knowledge could ultimately allow more targeted approaches for weight management treatment strategies. This trial was registered at clinicaltrials.gov as NCT02004821.

Omega-3 Fatty Acids and Adipose Tissue: Inflammation and Browning

2020 ◽  
Vol 40 (1) ◽  
pp. 25-49 ◽  
Author(s):  
Nishan Sudheera Kalupahana ◽  
Bimba Lakmini Goonapienuwala ◽  
Naima Moustaid-Moussa
Keyword(s):  
Fatty Acids ◽  
Weight Loss ◽  
Adipose Tissue ◽  
Metabolic Regulation ◽  
Energy Homeostasis ◽  
Molecular Mechanisms ◽  
Whole Body ◽  
Omega 3 ◽  
Brown Adipose ◽  
Body Energy

White adipose tissue (WAT) and brown adipose tissue (BAT) are involved in whole-body energy homeostasis and metabolic regulation. Changes to mass and function of these tissues impact glucose homeostasis and whole-body energy balance during development of obesity, weight loss, and subsequent weight regain. Omega-3 polyunsaturated fatty acids (ω-3 PUFAs), which have known hypotriglyceridemic and cardioprotective effects, can also impact WAT and BAT function. In rodent models, these fatty acids alleviate obesity-associated WAT inflammation, improve energy metabolism, and increase thermogenic markers in BAT. Emerging evidence suggests that ω-3 PUFAs can also modulate gut microbiota impacting WAT function and adiposity. This review discusses molecular mechanisms, implications of these findings, translation to humans, and future work, especially with reference to the potential of these fatty acids in weight loss maintenance.

scholarly journals Regulation of body temperature and brown adipose tissue thermogenesis by bombesin receptor subtype-3

2014 ◽  
Vol 306 (6) ◽  
pp. E681-E687 ◽  
Author(s):  
Dalya M. Lateef ◽  
Gustavo Abreu-Vieira ◽  
Cuiying Xiao ◽  
Marc L. Reitman
Keyword(s):  
Adipose Tissue ◽  
Body Temperature ◽  
Brown Adipose Tissue ◽  
Energy Homeostasis ◽  
Activity Level ◽  
Receptor Subtype ◽  
Reduced Body ◽  
Brown Adipose ◽  
Bombesin Receptor ◽  
Subtype 3

Bombesin receptor subtype-3 (BRS-3) regulates energy homeostasis, with Brs3 knockout ( Brs3−/y) mice being hypometabolic, hypothermic, and hyperphagic and developing obesity. We now report that the reduced body temperature is more readily detected if body temperature is analyzed as a function of physical activity level and light/dark phase. Physical activity level correlated best with body temperature 4 min later. The Brs3−/y metabolic phenotype is not due to intrinsically impaired brown adipose tissue function or in the communication of sympathetic signals from the brain to brown adipose tissue, since Brs3−/y mice have intact thermogenic responses to stress, acute cold exposure, and β3-adrenergic activation, and Brs3−/y mice prefer a cooler environment. Treatment with the BRS-3 agonist MK-5046 increased brown adipose tissue temperature and body temperature in wild-type but not Brs3−/y mice. Intrahypothalamic infusion of MK-5046 increased body temperature. These data indicate that the BRS-3 regulation of body temperature is via a central mechanism, upstream of sympathetic efferents. The reduced body temperature in Brs3−/y mice is due to altered regulation of energy homeostasis affecting higher center regulation of body temperature, rather than an intrinsic defect in brown adipose tissue.

scholarly journals The role of perivascular adipose tissue in vasoconstriction, arterial stiffness, and aneurysm

2015 ◽  
Vol 21 (2) ◽  
Author(s):  
Luis Villacorta ◽  
Lin Chang
Keyword(s):  
Adipose Tissue ◽  
Arterial Stiffness ◽  
Vascular Function ◽  
Molecular Mechanisms ◽  
Inflammatory Cells ◽  
Phenotypic Change ◽  
Neointimal Formation ◽  
Perivascular Adipose Tissue ◽  
Fat Depots ◽  
Brown Adipose

AbstractSince the “rediscovery” of brown adipose tissue in adult humans, significant scientific efforts are being pursued to identify the molecular mechanisms to promote a phenotypic change of white adipocytes into brown-like cells, a process called “browning”. It is well documented that white adipose tissue (WAT) mass and factors released from WAT influence the vascular function and positively correlate with cardiac arrest, stroke, and other cardiovascular complications. Similar to other fat depots, perivascular adipose tissue (PVAT) is an active endocrine organ and anatomically surrounds vessels. Both brown-like and white-like PVAT secrete various adipokines, cytokines, and growth factors that either prevent or promote the development of cardiovascular diseases (CVDs) depending on the relative abundance of each type and their bioactivity in the neighboring vasculature. Notably, pathophysiological conditions, such as obesity, hypertension, or diabetes, induce the imbalance of PVAT-derived vasoactive products that promote the infiltration of inflammatory cells. This then triggers derangements in vascular smooth muscle cells and endothelial cell dysfunction, resulting in the development of vascular diseases. In this review, we discuss the recent advances on the contribution of PVAT in CVDs. Specifically, we summarize the current proposed roles of PVAT in relationship with vascular contractility, endothelial dysfunction, neointimal formation, arterial stiffness, and aneurysm.

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