Resistance to Diet-Induced Obesity in Mice Lacking OPA1 in Adipose Tissue Occurs Independently of Fat-Derived FGF-21 and BAT Function

AbstractAdipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

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L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice

10.2337/figshare.14414216 ◽

2021 ◽

Author(s):

Wan-Qiu Peng ◽

Gang Xiao ◽

Bai-Yu Li ◽

Ying-Ying Guo ◽

Liang Guo ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Intraperitoneal Administration ◽

Dna Demethylation ◽

Active Dna Demethylation ◽

Diet Induced Obesity ◽

Elevated Expression ◽

Obesity In Mice

L-Theanine is a nonprotein amino acid with much beneficial efficacy. We found that intraperitoneal treatment of the mice with L-Theanine(100mg/kg/day) enhanced adaptive thermogenesis and induced the browning of inguinal white adipose tissue (iWAT) with elevated expression of Prdm16, Ucp1 and other thermogenic genes. Meanwhile, administration of the mice with L-Theanine increased energy expenditure. In vitro studies indicated that L-Theanine induced the development of brown-like features in adipocytes. The shRNA-mediated depletion of Prdm16 blunted the role of L-Theanine in promoting the brown-like phenotypes in adipocytes and in the iWAT of mice. L-Theanine treatment enhanced AMPKα phosphorylation both in adipocytes and in iWAT. Knockdown of AMPKα ablolished L-Theanine-induced upregulation of Prdm16 and adipocytes browning. L-Theanine increased the α-ketoglutarate (α-KG) level in adipocytes, which may increase the transcription of Prdm16 by inducing active DNA demethylation on its promoter. AMPK activation was required for L-Theanine-induced increase of α-KG and DNA demethylation on Prdm16 promoter. Moreover, intraperitoneal administration with L-Theanine ameliorated obesity, improved glucose tolerance and insulin sensitivity, and reduced plasma triglyceride, total cholesterol and free fatty acid in the high fat diet-fed mice. Our results suggest a potential role of L-Theanine in combating diet-induced obesity in mice, which may involve L-Theanine-induced browning of white adipose tissue.

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Sex differences during the course of diet-induced obesity in mice: adipose tissue expandability and glycemic control

International Journal of Obesity ◽

10.1038/ijo.2011.87 ◽

2011 ◽

Vol 36 (2) ◽

pp. 262-272 ◽

Cited By ~ 78

Author(s):

D Medrikova ◽

Z M Jilkova ◽

K Bardova ◽

P Janovska ◽

M Rossmeisl ◽

...

Keyword(s):

Sex Differences ◽

Adipose Tissue ◽

Glycemic Control ◽

Diet Induced Obesity ◽

Obesity In Mice ◽

Adipose Tissue Expandability

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L-Theanine Activates the Browning of White Adipose Tissue through the AMPK/α-Ketoglutarate/Prdm16 Axis and Ameliorates Diet-induced Obesity in Mice

Diabetes ◽

10.2337/db20-1210 ◽

2021 ◽

pp. db201210

Author(s):

Wan-Qiu Peng ◽

Gang Xiao ◽

Bai-Yu Li ◽

Ying-Ying Guo ◽

Liang Guo ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Diet Induced Obesity ◽

Obesity In Mice

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Genetic Deficiency of TRAF5 Promotes Adipose Tissue Inflammation and Aggravates Diet-Induced Obesity in Mice

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316677 ◽

2021 ◽

Author(s):

Mark Colin Gissler ◽

Nathaly Anto-Michel ◽

Jan Pennig ◽

Philipp Scherrer ◽

Xiaowei Li ◽

...

Keyword(s):

Adipose Tissue ◽

Visceral Adipose Tissue ◽

Obese Patients ◽

Adipose Tissue Inflammation ◽

Metabolic Complications ◽

Tissue Inflammation ◽

Diet Induced Obesity ◽

Genetic Deficiency ◽

Obesity In Mice ◽

Visceral Adipose

Objective: The accumulation of inflammatory leukocytes is a prerequisite of adipose tissue inflammation during cardiometabolic disease. We previously reported that a genetic deficiency of the intracellular signaling adaptor TRAF5 (TNF [tumor necrosis factor] receptor–associated factor 5) accelerates atherosclerosis in mice by increasing inflammatory cell recruitment. Here, we tested the hypothesis that an impairment of TRAF5 signaling modulates adipose tissue inflammation and its metabolic complications in a model of diet-induced obesity in mice. Approach and Results: To induce diet-induced obesity and adipose tissue inflammation, wild-type or Traf5 −/− mice consumed a high-fat diet for 18 weeks. Traf5 −/− mice showed an increased weight gain, impaired insulin tolerance, and increased fasting blood glucose. Weight of livers and peripheral fat pads was increased in Traf5 −/− mice, whereas lean tissue weight and growth were not affected. Flow cytometry of the stromal vascular fraction of visceral adipose tissue from Traf5 −/− mice revealed an increase in cytotoxic T cells, CD11c + macrophages, and increased gene expression of proinflammatory cytokines and chemokines. At the level of cell types, expression of TNFα, MIP (macrophage inflammatory protein)-1α, MCP (monocyte chemoattractant protein)-1, and RANTES (regulated on activation, normal T-cell expressed and secreted) was significantly upregulated in Traf5 -deficient adipocytes but not in Traf5 -deficient leukocytes from visceral adipose tissue. Finally, Traf5 expression was lower in adipocytes from obese patients and mice and recovered in adipose tissue of obese patients one year after bariatric surgery. Conclusions: We show that a genetic deficiency of TRAF5 in mice diet-induced obesity and its metabolic derangements by a proinflammatory response in adipocytes. Our data indicate that TRAF5 may promote anti-inflammatory and obesity-preventing signaling events in adipose tissue.

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Lactobacillus plantarum KFY04 prevents obesity in mice through the PPAR pathway and alleviates oxidative damage and inflammation

Food & Function ◽

10.1039/d0fo00519c ◽

2020 ◽

Vol 11 (6) ◽

pp. 5460-5472

Author(s):

Xingyao Long ◽

Xiaofei Zeng ◽

Fang Tan ◽

Ruokun Yi ◽

Yanni Pan ◽

...

Keyword(s):

Adipose Tissue ◽

Oxidative Damage ◽

Lactobacillus Plantarum ◽

High Fat Diet ◽

Adipocyte Size ◽

High Fat ◽

Diet Induced Obesity ◽

Obesity In Mice ◽

Ppar Pathway

Lactobacillus plantarum KFY04 can significantly inhibited the increase of adipocytes and decrease the adipocyte size in adipose tissue. LP-KFY04 can be used to mitigate high-fat-diet-induced obesity in mice.

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Enoxacin induces oxidative metabolism and mitigates obesity by regulating adipose tissue miRNA expression

Science Advances ◽

10.1126/sciadv.abc6250 ◽

2020 ◽

Vol 6 (49) ◽

pp. eabc6250

Author(s):

Andréa Livia Rocha ◽

Tanes Imamura de Lima ◽

Gerson Profeta de Souza ◽

Renan Oliveira Corrêa ◽

Danilo Lopes Ferrucci ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Mirna Expression ◽

Oxidative Metabolism ◽

Target Genes ◽

Cell Models ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Obesity In Mice

MicroRNAs (miRNAs) have been implicated in oxidative metabolism and brown/beige adipocyte identity. Here, we tested whether widespread changes in miRNA expression promoted by treatment with the small-molecule enoxacin cause browning and prevent obesity. Enoxacin mitigated diet-induced obesity in mice, and this was associated with increased energy expenditure. Consistently, subcutaneous white and brown adipose tissues and skeletal muscle of enoxacin-treated mice had higher levels of markers associated with thermogenesis and oxidative metabolism. These effects were cell autonomous since they were recapitulated in vitro in murine and human cell models. In preadipocytes, enoxacin led to a reduction of miR-34a-5p expression and up-regulation of its target genes (e.g., Fgfr1, Klb, and Sirt1), thus increasing FGF21 signaling and promoting beige adipogenesis. Our data demonstrate that enoxacin counteracts obesity by promoting thermogenic signaling and inducing oxidative metabolism in adipose tissue and skeletal muscle in a mechanism that involves, at least in part, miRNA-mediated regulation.

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