Up-regulation of adiponectin by resveratrol: The essential roles of the Akt/FOXO1 and amp-activated protein kinase signaling pathways and DsbA-L

Anping Wang, Meilian Liu, Xianling Liu, Lily Q. Dong, Randolph D. Glickman, Thomas J. Slaga, Zhiguang Zhou, Feng Liu

Research output: Contribution to journalArticlepeer-review

75 Scopus citations

Abstract

The natural polyphenol resveratrol (RSV) displays a wide spectrum of health beneficial activities, yet the precise mechanisms remain to be fully elucidated. Here we show that RSV promotes the multimerization and cellular levels of adiponectin in 3T3-L1 adipocytes. The stimulatory effect of RSV was not affected by knocking out Sirt1, but was diminished by suppressing the expression levels of DsbA-L, a recently identified adiponectin-interactive protein that promotes adiponectin multimerization. Suppression of the Akt signaling pathway resulted in an increase in the expression levels of DsbA-L and adiponectin. On the other hand, knocking out FOXO1 or suppressing the activity or expression levels of the AMP-activated protein kinase (AMPK) down-regulated DsbA-L and adiponectin. The stimulatory effect of RSV on adiponectin and DsbA-L expression was completely diminished in FOXO1-suppressed and AMPK-inactivated 3T3-L1 adipocytes. Taken together, our results demonstrate that RSV promotes adiponectin multimerization in 3T3-L1 adipocytes via a Sirt1-independent mechanism. In addition, we show that the stimulatory effect of RSV is regulated by both the Akt/FOXO1 and the AMPK signaling pathways. Last, we show that DsbA-L plays a critical role in the promoting effect of RSV on adiponectin multimerization and cellular levels.

Original languageEnglish (US)
Pages (from-to)60-66
Number of pages7
JournalJournal of Biological Chemistry
Volume286
Issue number1
DOIs
StatePublished - Jan 7 2011

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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