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Withaferin A Promotes White Adipose Browning and Prevents Obesity Through Sympathetic Nerve-Activated Prdm16-FATP1 Axis
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posted on 2021-11-03, 22:12 authored by Bingbing Guo, Jiarui Liu, Bingwei Wang, Chenyu Zhang, Zhijie Su, Miao Zhao, Lihua Qin, Weiguang Zhang, Ruimao ZhengThe increasing prevalence
of obesity has resulted in demands for the development of new effective
strategies for obesity treatment. The Withaferin A (WA) shows a great potential
for prevention of obesity by sensitizing leptin signaling in the hypothalamus.
However, the mechanism underlying the weight- and adiposity-reducing effects of
WA remains to be elucidated. Here, we report that WA treatment induced white
adipose tissue (WAT) browning, elevated energy expenditure (EE), decreased
respiratory exchange ratio (RER), and prevented high-fat diet (HFD)-induced
obesity. The sympathetic chemical denervation dampened the WAT browning and
also impeded the reduction of adiposity in WA-treated mice. WA markedly
up-regulated the levels of Prdm16 and FATP1 (Slc27a1) in the inguinal WAT (iWAT), and this was blocked
by sympathetic denervation. Prdm16 or FATP1 knockdown in iWAT abrogated the WAT
browning-inducing effects of WA, and restored the weight gain and adiposity in
WA-treated mice. Together, these findings suggest that WA induces WAT browning
through the sympathetic nerve-adipose axis; and the adipocytic Prdm16-FATP1
pathway mediates the promotive effects of WA on white adipose browning.