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.