Butein-Enriched Fractions of Butea monosperma (Lam.) Taub. Flower Decrease Weight Gains and Increase Energy Expenditure in High-Fat Diet-Induced Obese Mice

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.

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

International Journal of Molecular Sciences ◽

10.3390/ijms20010026 ◽

2018 ◽

Vol 20 (1) ◽

pp. 26 ◽

Cited By ~ 4

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.

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

Phytotherapy Research ◽

10.1002/ptr.6800 ◽

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

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Withaferin A exerts an anti-obesity effect by increasing energy expenditure through thermogenic gene expression in high-fat diet-fed obese mice

Phytomedicine ◽

10.1016/j.phymed.2020.153457 ◽

2020 ◽

pp. 153457

Author(s):

Da-Hye Lee ◽

So-Hyn Park ◽

Eunyoung Lee ◽

Hyo-Deok Seo ◽

Jiyun Ahn ◽

...

Keyword(s):

Gene Expression ◽

Energy Expenditure ◽

High Fat Diet ◽

Withaferin A ◽

Obese Mice ◽

High Fat

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Prior exercise training blunts short-term high-fat diet-induced weight gain

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00072.2016 ◽

2016 ◽

Vol 311 (2) ◽

pp. R315-R324 ◽

Cited By ~ 11

Author(s):

Laelie A. Snook ◽

Rebecca E. K. MacPherson ◽

Cynthia M. F. Monaco ◽

Scott Frendo-Cumbo ◽

Laura Castellani ◽

...

Keyword(s):

Adipose Tissue ◽

Weight Gain ◽

Energy Expenditure ◽

Exercise Training ◽

Glucose Intolerance ◽

High Fat Diet ◽

Treadmill Running ◽

High Fat ◽

Prior Exercise ◽

Increase Energy Expenditure

High-fat diets rapidly cause weight gain and glucose intolerance. We sought to determine whether these changes could be mitigated with prior exercise training. Male C57BL/6J mice were exercise-trained by treadmill running (1 h/day, 5 days/wk) for 4 wk. Twenty-four hours after the final bout of exercise, mice were provided with a high-fat diet (HFD; 60% kcal from lard) for 4 days, with no further exercise. In mice fed the HFD prior to exercise training, the results were blunted weight gain, reduced fat mass, and a slight attenuation in glucose intolerance that was mirrored by greater insulin-induced Akt phosphorylation in skeletal muscle compared with sedentary mice fed the HFD. When ad libitum-fed sedentary mice were compared with sedentary high-fat fed mice that were calorie restricted (−30%) to match the weight gain of the previously trained high-fat fed mice, the same attenuated impairments in glucose tolerance were found. Blunted weight gain was associated with a greater capacity to increase energy expenditure in trained compared with sedentary mice when challenged with a HFD. Although mitochondrial enzymes in white adipose tissue and UCP-1 protein content in brown adipose tissue were increased in previously exercised compared with sedentary mice fed a HFD, ex vivo mitochondrial respiration was not increased in either tissue. Our data suggest that prior exercise training attenuates high-fat diet-induced weight gain and glucose intolerance and is associated with a greater ability to increase energy expenditure in response to a high-fat diet.

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

Current Developments in Nutrition ◽

10.1093/cdn/nzz031.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).

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