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Each oligomeric form of adiponectin exerts non\u2010overlapping biological functions, with the HMW oligomer possessing the most potent insulin\u2010sensitizing activity. In this study, we reported that emodin, a natural product and active ingredient of various Chinese herbs, activates AMPK in both 3T3\u2010L1 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\u2010L1 adipocytes. Emodin might activate AMPK by an indirect mechanism similar to berberine. We also found that emodin activates PPAR\u03b3 and promotes differentiation and adiponectin expression during differentiation of 3T3\u2010L1 preadipocytes. Therefore, emodin is a novel AMPK activator with PPAR\u03b3\u2010agonist activity. Our results demonstrate that the effects of emodin on adiponectin expression and multimerization are the ultimate effects resulting from both AMPK activation and PPAR\u03b3 activation. The dual\u2010activity makes emodin or the derivatives potential drug candidates for the treatment of type 2 diabetes and other obesity\u2010related metabolic diseases. J. Cell. Biochem. 113: 3547\u20133558, 2012. \u00a9 2012 Wiley Periodicals, Inc.<\/jats:p>","DOI":"10.1002\/jcb.24232","type":"journal-article","created":{"date-parts":[[2012,6,21]],"date-time":"2012-06-21T20:50:37Z","timestamp":1340311837000},"page":"3547-3558","source":"Crossref","is-referenced-by-count":56,"title":["Promotion of adiponectin multimerization by emodin: A novel AMPK activator with PPAR\u03b3\u2010agonist 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