Piceatannol antagonizes lipolysis by promoting autophagy-lysosome-dependent degradation of lipolytic protein clusters in adipocytes

文献类型： 外文期刊

第一作者： Kwon, Jung Yeon

作者： Kwon, Jung Yeon;Kershaw, Jonathan;Chen, Chih-Yu;Zhu, Yuyan;Myer, Phillip R.;Applegate, Bruce;Kim, Kee-Hong;Kwon, Jung Yeon;Kwon, Jung Yeon;Kershaw, Jonathan;Chen, Chih-Yu;Chen, Chih-Yu;Komanetsky, Susan M.;Komanetsky, Susan M.;Zhu, Yuyan;Guo, Xiaoxuan;Myer, Phillip R.;Applegate, Bruce

作者机构：

关键词： Adipocytes; ATGL; Autophagy; Degradation; Lipolysis; Piceatannol

期刊名称：JOURNAL OF NUTRITIONAL BIOCHEMISTRY （ 影响因子：6.117； 五年影响因子：6.287 ）

ISSN： 0955-2863

年卷期： 2022 年 105 卷

页码：

收录情况： SCI

摘要： Overly elevated circulating non-esterified fatty acids (NEFAs) is an emerging health concern of obesity-associated energy disorders. However, methods to reduce circulating NEFAs remain elusive. The present study determined the effect of piceatannol, a naturally occurring stilbene, on adipocyte lipolysis and its underlying mechanism. Differentiated 3T3-L1 adipocytes, brown adipocytes and isolated white adipose tissue were treated with various concentrations of piceatannol for 1.5-h both in the basal and stimulated lipolysis conditions. Piceatannol significantly inhibited NEFAs and glycerol release with a concomitant reduction of ATGL, CGI-58 and PLIN1 expression in adipocytes. Using a series of inhibitor assays, piceatannol-induced degradation of these proteins was found to be mediated by upregulation of the autophagy-lysosome pathway. Moreover, we demonstrated that piceatannol is capable of stimulating autophagy in vitro . Importantly, piceatannol administration tended to lower fasting-induced serum glycerol levels in healthy mice. Furthermore, piceatannol administration lowered lipolysis, central adiposity and hyperinsulinemia in diet-induced obese mice. Our study provides profound evidence of a novel inhibitory role of piceatannol in lipolysis through autophagy-lysosome-dependent degradation of the key lipolytic proteins in adipocytes. This study offers a mechanistic foundation for investigating the potential of piceatannol-containing foods in reducing lipolysis and its associated metabolic disorders. (c) 2022 Elsevier Inc. All rights reserved.

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