Pyrazolone derivative C29 protects against HFD-induced obesity in mice via activation of AMPK in adipose tissue

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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Redistribution of substrates to adipose tissue promotes obesity in mice with selective insulin resistance in muscle

Journal of Clinical Investigation ◽

10.1172/jci8305 ◽

2000 ◽

Vol 105 (12) ◽

pp. 1791-1797 ◽

Cited By ~ 233

Author(s):

Jason K. Kim ◽

M. Dodson Michael ◽

Stephen F. Previs ◽

Odile D. Peroni ◽

Franck Mauvais-Jarvis ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Obesity In Mice

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Role of A 1 and A 2A adenosine receptor agonists in adipose tissue inflammation induced by obesity in mice

European Journal of Pharmacology ◽

10.1016/j.ejphar.2017.02.017 ◽

2017 ◽

Vol 799 ◽

pp. 154-159 ◽

Cited By ~ 15

Author(s):

Caroline Candida DeOliveira ◽

Cintia Rabelo e Paiva Caria ◽

Erica Martins Ferreira Gotardo ◽

Marcelo Lima Ribeiro ◽

Alessandra Gambero

Keyword(s):

Adipose Tissue ◽

Adenosine Receptor ◽

Adipose Tissue Inflammation ◽

Adenosine Receptor Agonists ◽

Tissue Inflammation ◽

Receptor Agonists ◽

Obesity In Mice

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Macadamia Oil Supplementation Attenuates Inflammation and Adipocyte Hypertrophy in Obese Mice

Mediators of Inflammation ◽

10.1155/2014/870634 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Edson A. Lima ◽

Loreana S. Silveira ◽

Laureane N. Masi ◽

Amanda R. Crisma ◽

Mariana R. Davanso ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Lipid Profile ◽

High Fat Diet ◽

Control Diet ◽

Saturated Fatty Acids ◽

Peritoneal Macrophages ◽

High Fat ◽

Obesity In Mice ◽

Adipocyte Hypertrophy

Excess of saturated fatty acids in the diet has been associated with obesity, leading to systemic disruption of insulin signaling, glucose intolerance, and inflammation. Macadamia oil administration has been shown to improve lipid profile in humans. We evaluated the effect of macadamia oil supplementation on insulin sensitivity, inflammation, lipid profile, and adipocyte size in high-fat diet (HF) induced obesity in mice. C57BL/6 male mice (8 weeks) were divided into four groups: (a) control diet (CD), (b) HF, (c) CD supplemented with macadamia oil by gavage at 2 g/Kg of body weight, three times per week, for 12 weeks (CD + MO), and (d) HF diet supplemented with macadamia oil (HF + MO). CD and HF mice were supplemented with water. HF mice showed hypercholesterolemia and decreased insulin sensitivity as also previously shown. HF induced inflammation in adipose tissue and peritoneal macrophages, as well as adipocyte hypertrophy. Macadamia oil supplementation attenuated hypertrophy of adipocytes and inflammation in the adipose tissue and macrophages.

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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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Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity

International Journal of Molecular Sciences ◽

10.3390/ijms222111745 ◽

2021 ◽

Vol 22 (21) ◽

pp. 11745

Author(s):

Ignacio Colón-Mesa ◽

Marta Fernández-Galilea ◽

Neira Sáinz ◽

Marta Lopez-Yus ◽

Jose M. Artigas ◽

...

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Subcutaneous White Adipose Tissue ◽

Visceral Fat Accumulation ◽

Fat Depots ◽

Adipose Tissue Depots ◽

Obesity In Mice ◽

Cdk2 Expression ◽

Lower Expression

Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot’s metabolic differences. Further studies are necessary to fully corroborate this hypothesis.

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