Cidec promotes the differentiation of human adipocytes by degradation of AMPKα through ubiquitin-proteasome pathway.

We previously showed that Cidec was localized on the surface of lipid droplets and could promote the differentiation of human adipocytes, but the molecular mechanism was still unknown. In this study, we first sought to identify proteins that interact with Cidec using yeast two-hybrid system. The results revealed that Cidec could directly interact with AMPKα1 subunit. We further showed that AMPKα levels decreased while Cidec increased during the adipogenic differentiation of human adipocytes. Meanwhile, we observed that the increased Cidec could reduce AMPKα level in adipocytes, and the downregulation of AMPKα could help to promote the differentiation of adipocytes. The results of co-immunoprecipitation and immunofluorescent proved that Cidec biochemically interacted and co-localized with AMPKα1, which meant Cidec was a regulator for AMPKα stability through an ubiquitin-proteasome pathway. Our data suggested that Cidec could interact with and down-regulate AMPKα through an ubiquitin-proteasome degradation pathway, which provided a possible mechanism of Cidec in promoting human adipocytes differentiation. Our work proposed a new possible mechanism for human adipogenesis, and also provided a potential role of AMPKα as a target in treating obesity or obesity-related diseases.