Up-regulation of adiponectin by resveratrol: the essential roles of the Akt/FOXO1 and AMP-activated protein kinase signaling pathways and DsbA-L.
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.
Wang
Anping
A
Metabolic Syndrome Research Center, Second Xiangya Hospital, Central South University, Hunan 410011, China.
Liu
Meilian
M
Liu
Xianling
X
Dong
Lily Q
LQ
Glickman
Randolph D
RD
Slaga
Thomas J
TJ
Zhou
Zhiguang
Z
Liu
Feng
F
D041721:3T3-L1 Cells; D055372:AMP-Activated Protein Kinases / Q000378:metabolism; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D052242:Adiponectin / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000378:metabolism*; D005982:Glutathione Transferase / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D055503:Protein Multimerization / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D020836:Protein Structure, Quaternary; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D034622:RNA Interference; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D000077185:Resveratrol; D015398:Signal Transduction / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects*
D052242:Adiponectin; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; C467200:Foxo1 protein, mouse; D000081382:Pyruvate Dehydrogenase Acetyl-Transferring Kinase; D012333:RNA, Messenger; D013267:Stilbenes; D005982:Glutathione Transferase; D017346:Protein Serine-Threonine Kinases; D051057:Proto-Oncogene Proteins c-akt; D055372:AMP-Activated Protein Kinases; D000077185:Resveratrol