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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 03.11.2021, 22:12 by Bingbing Guo, Jiarui Liu, Bingwei Wang, Chenyu Zhang, Zhijie Su, Miao Zhao, Lihua Qin, Weiguang Zhang, Ruimao Zheng
The 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.

Funding

This work was supported by grants from the National Key Research and Development Program of China (2017YFC1700402 to R.Z.), the National Natural Science Foundation of China (No.81471064. No. 81670779 and No. 81870590 to R.Z), the Beijing Municipal Natural Science Foundation (No. 7162097 and No. H2018206641 to R.Z), and the Peking University Research Foundation (No. BMU20140366 to R.Z).

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