Adiponectin promotes myogenic differentiation via a Mef2C-AdipoR1 positive feedback loop.

Adiponectin is an important hormone that regulates systemic metabolism, and it has been reported that globular adiponectin promotes myogenic differentiation. However, the mechanisms by which adiponectin promotes myogenic differentiation is not fully understood. In the present study, we show that adiponectin and its receptor 1 are significantly up-regulated during myogenic differentiation and that adiponectin increased the expression level of a core myogenic regulator, Mef2C, which is required for the effects of adiponectin on promoting myogenic differentiation. A transcriptional inhibitor of Mef2C, HDAC9, was down-regulated by adiponectin. In turn, Mef2C overexpression up-regulates adiponectin and its receptor, AdipoR1, to increase myogenic differentiation. We showed that mechanistically, Mef2C directly binds to AdipoR1 promoter to transcriptionally up-regulate AdipoR1 expression, which is required for the effects of Mef2C overexpression on myogenic differentiation. Thus, adiponectin/AdipoR1 and Mef2c form a positive feedback loop to promote myogenic differentiation.