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

• Published in: Phytomedicine (Stuttgart) 2021-02, Vol.82, p.153457, Article 153457
• Main Authors: Lee, Da-Hye, Park, So-Hyun, Lee, Eunyoung, Seo, Hyo-Deok, Ahn, Jiyun, Jang, Young-Jin, Ha, Tae-Youl, Im, Seung Soon, Jung, Chang Hwa
• Format: Article
• Language: English
• Subjects: Adipose tissue browning; Adipose Tissue, Brown - drug effects; Adipose Tissue, Brown - metabolism; Adipose Tissue, White - drug effects; Adipose Tissue, White - metabolism; AMP-activated protein kinase; AMP-Activated Protein Kinases - metabolism; Animals; Anti-Obesity Agents - pharmacology; Body Weight - drug effects; Diet, High-Fat; Energy expenditure; Energy Metabolism - drug effects; Gene Expression - drug effects; Male; Mice; Mice, Inbred C57BL; Mice, Obese; Mitochondria - metabolism; Mitochondrial activity; Mitogen-activated protein kinase; Obesity - drug therapy; Thermogenesis - drug effects; Thermogenesis - genetics; Uncoupling Protein 1 - metabolism; Withaferin A; Withania - chemistry; Withanolides - pharmacology; Withanolides - therapeutic use
• ISSN: 0944-7113; 1618-095X
• DOI: 10.1016/j.phymed.2020.153457

lWFA supplementation prevent HFD-induced obesity.lWFA treatment increased oxygen consumption in obese mice.lWFA improved mitochondrial activity in BAT and promotes of the browning of scWAT.lWFA activated MAPK signaling and AMPK in adipose tissue. The enhancement of energy expenditure has attracted attention as a therapeutic target for the management of body weight. Withaferin A (WFA), a major constituent of Withania somnifera extract, has been reported to possess anti-obesity properties, however the underlying mechanism remains unknown. To investigate whether WFA exerts anti-obesity effects via increased energy expenditure, and if so, to characterize the underlying pathway. C57BL/6 J mice were fed a high-fat diet (HFD) for 10 weeks, and WFA was orally administered for 7 days. The oxygen consumption rate of mice was measured at 9 weeks using an OxyletPro™ system. Hematoxylin and eosin (H&E), immunohistochemistry, immunoblotting, and real-time PCR methods were used. Treatment with WFA ameliorated HFD-induced obesity by increasing energy expenditure by improving of mitochondrial activity in brown adipose tissue (BAT) and promotion of subcutaneous white adipose tissue (scWAT) browning via increasing uncoupling protein 1 levels. WFA administration also significantly increased AMP-activated protein kinase (AMPK) phosphorylation in the BAT of obese mice. Additionally, WFA activated mitogen-activated protein kinase (MAPK) signaling, including p38/extracellular signal-regulated kinase MAPK, in both BAT and scWAT. WFA enhances energy expenditure and ameliorates obesity via the induction of AMPK and activating p38/extracellular signal-regulated kinase MAPK, which triggers mitochondrial biogenesis and browning-related gene expression. [Display omitted]