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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

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Author(s)
Da-Hye LeeSo-Hyun ParkEunyoung LeeHyo-Deok SeoJiyun AhnYoung-Jin JangTae-Youl HaSeung Soon ImChang Hwa Jung
Keimyung Author(s)
Im, Seung Soon
Department
Dept. of Physiology (생리학)
Journal Title
Phytomedicine
Issued Date
2021
Volume
82
Keyword
AMP-activated protein kinaseAdipose tissue browningEnergy expenditureMitochondrial activityMitogen-activated protein kinaseWithaferin A
Abstract
Background:
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.

Purpose:
To investigate whether WFA exerts anti-obesity effects via increased energy expenditure, and if so, to characterize the underlying pathway.

Methods:
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.

Results:
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.

Conclusion:
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.
Keimyung Author(s)(Kor)
임승순
Publisher
School of Medicine (의과대학)
Citation
Da-Hye Lee et al. (2021). Withaferin A exerts an anti-obesity effect by increasing energy expenditure through thermogenic gene expression in high-fat diet-fed obese mice. Phytomedicine, 82, 153457. doi: 10.1016/j.phymed.2020.153457
Type
Article
ISSN
0944-7113
Source
https://www.sciencedirect.com/science/article/abs/pii/S0944711320302889
DOI
10.1016/j.phymed.2020.153457
URI
https://kumel.medlib.dsmc.or.kr/handle/2015.oak/43480
Appears in Collections:
1. School of Medicine (의과대학) > Dept. of Physiology (생리학)
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