Adipose induces myoblast differentiation and mediates TNFα-regulated myogenesis

Skeletal muscle formation is controlled by multiple processes. These processes are tightly regulated by muscle regulatory factors. Genes that are highly and specifically expressed during myogenesis need to be identified. In the present study, the role of an anti-adipogenic gene adipose (Adp) in myogenesis is demonstrated. We discover that the expression of Adp is increased during myoblast differentiation. Overexpression of Adp in mouse myoblast C2C12 cells leads to an increase of myogenesis and up-regulation of MyoG expression. The inhibition effect of tumor necrosis factor α (TNFα) on myogenic differentiation is reversed by Adp-overexpression. Further research showed that TNFα significantly decreases Adp expression at both the mRNA and protein levels. Luciferase reporter assays showed that TNFα can inhibit Adp gene promoter activity and impair gene transcription. KLF15 was found to regulate the transcription of Adp. Furthermore, the expression of KLF15 and its binding to Adp promoter were reduced due to TNFα treatment. The reduced KLF15 expression after TNFα treatment is responsible for the repression of Adp gene promoter activity. KLF15 was also found to participate in Adp-mediated myogenic differentiation. Taken together, these data identify Adp as a positive modulator of myoblast differentiation and provide new insights for Adp function research.