Promotion of adiponectin multimerization by emodin: a novel AMPK activator with PPARγ-agonist activity.
Adiponectin is an important insulin-sensitizing adipokine with multiple beneficial effects on obesity-associated medical complications. It is secreted from adipocytes into circulation as high, medium, and low molecular weight forms (HMW, MMW, and LMW). Each oligomeric form of adiponectin exerts non-overlapping biological functions, with the HMW oligomer possessing the most potent insulin-sensitizing activity. In this study, we reported that emodin, a natural product and active ingredient of various Chinese herbs, activates AMPK in both 3T3-L1 adipocytes and 293T cells. Activation of AMPK by emodin promotes the assembly of HMW adiponectin and increases the ratio of HMW adiponectin to total adiponectin in 3T1-L1 adipocytes. Emodin might activate AMPK by an indirect mechanism similar to berberine. We also found that emodin activates PPARγ and promotes differentiation and adiponectin expression during differentiation of 3T3-L1 preadipocytes. Therefore, emodin is a novel AMPK activator with PPARγ-agonist activity. Our results demonstrate that the effects of emodin on adiponectin expression and multimerization are the ultimate effects resulting from both AMPK activation and PPARγ activation. The dual-activity makes emodin or the derivatives potential drug candidates for the treatment of type 2 diabetes and other obesity-related metabolic diseases.
MOE Key Laboratory of Bioinformatics, School of Life Sciences, Tsinghua University, Beijing 100084, China.
Zhifen
Z
Chen
Lu
L
Zhang
Junyang
J
Yi
Zhuanbo
Z
Yang
Zhijie
Z
Zhang
Zhen
Z
Li
D000091162:AMP-Activated Protein Kinase Kinases; D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D052242:Adiponectin / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D002460:Cell Line; D004642:Emodin / Q000494:pharmacology*; D004789:Enzyme Activation / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects; D017930:Genes, Reporter; D057809:HEK293 Cells; D006801:Humans; D008156:Luciferases; D051379:Mice; D008970:Molecular Weight; D047495:PPAR gamma / Q000819:agonists* / Q000235:genetics / Q000378:metabolism; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D011494:Protein Kinases / Q000235:genetics / Q000378:metabolism*; D055503:Protein Multimerization / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects
D052242:Adiponectin; D047495:PPAR gamma; D020033:Protein Isoforms; D047428:Protein Kinase Inhibitors; D008156:Luciferases; D011494:Protein Kinases; D000091162:AMP-Activated Protein Kinase Kinases; D004642:Emodin