The switch role of the Tmod4 in the regulation of balanced development between myogenesis and adipogenesis.

Tmod4 (Tropomodulin 4) is a member of Tmod family that plays important role in thin filament length regulation and myofibril assembly. We found that the expression levels of Tmod4 were higher in skeletal muscle and adipose tissues. However, the function and regulation of the Tmod4 gene in the myogenesis and adipogenesis remains unclear. In this study, we found that the expression of Tmod4 was decreased in myogenesis while increased in adipogenesis. Then, the transcriptional regulation analysis of Tmod4 promoter showed that Tmod4 could be regulated directly by myogenic factors and adipogenic factors. Furthermore, the roles of Tmod4 in the myogenesis and adipogenesis were confirmed by its over-expression in C2C12 cells and 3T3 cells, which suggested that Tmod4 could promote adipogenesis by up-regulating the adipogenic factors but moderately delay the myogenesis. These results indicated that the Tmod4 gene may play as a switch between myogenesis and adipogenesis, which resulted in the balanced development between skeletal muscle and adipose tissue. Therefore, the model for switch role of the Tmod4 in the balanced regulation between myogenesis and adipogenesis was proposed. It is showed that the expression of Tmod4 was activated in adipogenesis by adipogenic factors while inhibited in myogenesis by myogenic factors. Moreover, Tmod4 could promote adipogenesis by up-regulating the expression of adipogenic factors while moderately delaying the myogenesis. Our study provides an important basis for further understanding the regulation and function of porcine Tmod4 in muscle and fat development.