Metabolic Syndrome Research Center, Second Xiangya Hospital, Central South University, Hunan 410011, China.
J Biol Chem. 2011 Jan 7;286(1):60-6. doi: 10.1074/jbc.M110.188144. Epub 2010 Oct 27.
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.
天然多酚白藜芦醇（RSV）具有广泛的有益健康的活性，但确切的机制仍有待充分阐明。在这里，我们表明 RSV 可促进 3T3-L1 脂肪细胞中脂联素的多聚化和细胞水平。RSV 的刺激作用不受 Sirt1 敲除的影响，但通过抑制最近发现的促进脂联素多聚化的脂联素相互作用蛋白 DsbA-L 的表达水平而减弱。抑制 Akt 信号通路会导致 DsbA-L 和脂联素的表达水平增加。另一方面，敲除 FOXO1 或抑制 AMP 激活的蛋白激酶 (AMPK) 的活性或表达水平会下调 DsbA-L 和脂联素。在 FOXO1 抑制和 AMPK 失活的 3T3-L1 脂肪细胞中，RSV 对脂联素和 DsbA-L 表达的刺激作用完全减弱。总之，我们的结果表明 RSV 通过一种不依赖 Sirt1 的机制促进 3T3-L1 脂肪细胞中脂联素的多聚化。此外，我们表明 RSV 的刺激作用受 Akt/FOXO1 和 AMPK 信号通路的调节。最后，我们表明 DsbA-L 在 RSV 促进脂联素多聚化和细胞水平中的作用中起着关键作用。
