Up-regulation of Adiponectin by resveratrol: the essential
roles of the Akt/FOXO1 and AMP-activated protein kinase
signaling pathways and DsbA-L.
J Biol Chem. 2011 Jan 7;286(1):60-6.Metabolic Syndrome Research Center, Second Xiangya Hospital, Central South University,
Hunan 410011, China.
OBJECTIVE: 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.
METHODS AND RESULTS: 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.
CONCLUSIONS: 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.