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

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

Research output: Journal article publicationJournal articleAcademic researchpeer-review

3 Citations (Scopus)

Abstract

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.

Original languageEnglish
Article number108998
JournalJournal of Nutritional Biochemistry
Volume105
DOIs
Publication statusPublished - Jul 2022

Keywords

  • Adipocytes
  • ATGL
  • Autophagy
  • Degradation
  • Lipolysis, Piceatannol

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Molecular Biology
  • Nutrition and Dietetics
  • Clinical Biochemistry

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