Celastrol alleviates metabolic disturbance in high‐fat diet‐induced obese mice through increasing energy expenditure by ameliorating metabolic inflammation

2020 ◽  
Author(s):  
Xueping Yang ◽  
Fan Wu ◽  
Lingli Li ◽  
Ernest C. Lynch ◽  
Linglin Xie ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
High Fat Diet ◽  
Metabolic Disturbance ◽  
Obese Mice ◽  
High Fat ◽  
Metabolic Inflammation

scholarly journals Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

2019 ◽  
Vol 7 (1) ◽  
pp. e000783 ◽  
Author(s):  
Liang Xu ◽  
Naoto Nagata ◽  
Guanliang Chen ◽  
Mayumi Nagashimada ◽  
Fen Zhuge ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Chronic Inflammation ◽  
Plasma Levels ◽  
High Fat Diet ◽  
Macrophage Activation ◽  
Low Grade ◽  
Obese Mice ◽  
High Fat

ObjectiveWe reported previously that empagliflozin—a sodium-glucose cotransporter (SGLT) 2 inhibitor—exhibited preventive effects against obesity. However, it was difficult to extrapolate these results to human subjects. Here, we performed a therapeutic study, which is more relevant to clinical situations in humans, to investigate antiobesity effects of empagliflozin and illustrate the mechanism underlying empagliflozin-mediated enhanced fat browning in obese mice.Research design and methodsAfter 8 weeks on a high-fat diet (HFD), C57BL/6J mice exhibited obesity, accompanied by insulin resistance and low-grade chronic inflammation. Cohorts of obese mice were continued on the HFD for an additional 8-week treatment period with or without empagliflozin.ResultsTreatment with empagliflozin for 8 weeks markedly increased glucose excretion in urine, and suppressed HFD-induced weight gain, insulin resistance and hepatic steatosis. Notably, empagliflozin enhanced oxygen consumption and carbon dioxide production, leading to increased energy expenditure. Consistently, the level of uncoupling protein 1 expression was increased in both brown and white (WAT) adipose tissues of empagliflozin-treated mice. Furthermore, empagliflozin decreased plasma levels of interleukin (IL)-6 and monocyte chemoattractant protein-1, but increased plasma levels of IL-33 and adiponectin in obese mice. Finally, we found that empagliflozin reduced M1-polarized macrophage accumulation, while inducing the anti-inflammatory M2 phenotype of macrophages in the WAT and liver, thereby attenuating obesity-related chronic inflammation.ConclusionsTreatment with empagliflozin attenuated weight gain by increasing energy expenditure and adipose tissue browning, and alleviated obesity-associated inflammation and insulin resistance by alternative macrophage activation in the WAT and liver of obese mice.

scholarly journals Oxyresveratrol Increases Energy Expenditure through Foxo3a-Mediated Ucp1 Induction in High-Fat-Diet-Induced Obese Mice

2018 ◽  
Vol 20 (1) ◽  
pp. 26 ◽  
Author(s):  
Jin Choi ◽  
No-Joon Song ◽  
A Lee ◽  
Dong Lee ◽  
Min-Ju Seo ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Metabolic Diseases ◽  
Biological Activities ◽  
Obese Mice ◽  
High Fat ◽  
White Adipocyte

The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases.

scholarly journals Gene Therapy for Follistatin Mitigates Systemic Metabolic Inflammation and Post-Traumatic Osteoarthritis in High-Fat Diet-Induced Obese Mice

2019 ◽  
Author(s):  
Ruhang Tang ◽  
Natalia S. Harasymowicz ◽  
Chia-Lung Wu ◽  
Kelsey H. Collins ◽  
Yun-Rak Choi ◽  
...  
Keyword(s):  
Gene Therapy ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Joint Injury ◽  
Metabolic Inflammation ◽  
Knee Oa ◽  
Muscle Formation ◽  
Oxphos System ◽  
Post Traumatic

ABSTRACTObesity-associated inflammation and loss of muscle function play critical roles in the development of osteoarthritis (OA); thus, therapies that target muscle tissue may provide novel approaches to restoring metabolic and biomechanical dysfunction associated with obesity. Recent studies indicate that follistatin (FST), a protein which binds myostatin and activin, may have the potential to enhance muscle formation while neutralizing inflammation induced by these proteins. Here, we hypothesized that adeno-associated virus (AAV9) delivery of FST will enhance muscle formation and mitigate metabolic inflammation and knee OA caused by a high fat diet in mice. Obese mice receiving AAV-mediated FST delivery exhibited decreased inflammatory adipokines and cytokines systemically in the serum as well as locally in the joint synovial fluid. Regardless of diet, mice receiving FST gene therapy were protected from post-traumatic OA and bone remodeling induced by joint injury. While obesity disrupted the mitochondrial oxidative phosphorylation (OXPHOS) system in adipocytes, gene therapy for FST restored the key proteins involved in mitochondrial biogenesis, such as PPARγ coactivator 1α and AKT protein kinase 1, leading to the browning of white adipose tissue. Taken together, these findings suggest that FST gene therapy may provide a multifactorial therapeutic approach for injury-induced OA and metabolic inflammation in obesity.

scholarly journals A Berberis Microphylla Extract Prevents Obesity, Modulates Inflammation and Promotes Thermogenesis in Mice Fed on a High Fat Diet (P06-055-19)

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Lissette Duarte ◽  
Luis Amanda Ramirez ◽  
Javier Quezada ◽  
Carlos Poblete ◽  
Francisca Concha ◽  
...  
Keyword(s):  
Body Weight ◽  
Energy Expenditure ◽  
High Fat Diet ◽  
Control Diet ◽  
Obese Mice ◽  
High Fat ◽  
Final Body Weight ◽  
Funding Sources ◽  
Tnf Α ◽  
Body Weight Increase

Abstract Objectives To evaluate the effect of a polyphenol-rich berberis microphylla (Calafate, a Chilean native berry) extract in obese mice. Methods 40 8-week old C57BL6 mice were divided (n = 10 each) in 4 treatments for 4 months: Control diet (C; 11% fat), Control diet/Calafate (CC), High fat diet (HF; 58% fat), and High fat diet/Calafate (HFC). Animals received food and water ad libitum. CC and HFC were treated with a daily dose of 50 mg total polyphenols/kg weight of Calafate extract. IPGTT and indirect calorimetry were performed at month 2 and 3 respectively. At month 4, animals were euthanized and final body weight were recorded, and samples of interscapular brown (BAT), epididymal white (eWAT) and inguinal white (iWAT) adipose tissues were obtained. Gene expression of inflammatory markers (MCP-1, TNF-α, Leptina, ADIPOQ and F4/80) on eWAT and thermogenic markers (UCP-1, PGC1α, SIRT1, PRDM16, PPARα/γ, DIO2) on BAT and iWAT were analyzed. 2x2 ANOVA statistical analysis was applied. Results HF presented higher body weight than HFC mice (p < 0.001), from day 40 of treatment. Also, BAT weight was increased (p < 0.05). Basal glycemia was higher in HF than C (p < 0.05), but not than HFC. Energy expenditure was higher in HFC (p < 0.05). Differential expression of MCP-1, leptin and F4/80 on eWAT was detected. In BAT, UCP-1, PGC1α, PPARα and SIRT1 expression were higher in HFC than HF (p < 0.05). In iWAT, expression of PGC1α, PPARα, PRDM16, SIRT1, y DIO2 were also increased (p < 0.05). Conclusions a polyphenol-rich Calafate extract decrease body weight increase, augment BAT mass, modulate inflammation, and promote energy expenditure, which was related to higher expression of thermogenic genes in obese mice. Funding Sources FONDECYT 1171550 (CONICYT, CHILE).

Topical Application of Capsaicin Reduces Visceral Adipose Fat by Affecting Adipokine Levels in High-Fat Diet-Induced Obese Mice

Obesity ◽  
2012 ◽  
Author(s):  
Gong-Rak Lee ◽  
Mi Kyung Shin ◽  
Dong-Joon Yoon ◽  
Ah-Ram Kim ◽  
Rina Yu ◽  
...  
Keyword(s):  
Topical Application ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Visceral Adipose

Proteomic analysis of the anti-obesity effect of Taeumjowui-Tang in high fat diet-induced obese mice

Planta Medica ◽  
2016 ◽  
Vol 81 (S 01) ◽  
pp. S1-S381
Author(s):  
E Changkyun Park ◽  
SY Lee ◽  
SH Yun ◽  
WY Kim ◽  
Y Yi ◽  
...  
Keyword(s):  
Proteomic Analysis ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat
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