Identification Of S100A16as A Novel Adipogenesis Promoting Factor

Obesity is one kind of common chronic diseases. Patients with obesity andassociated metabolic disturbances have a significantly increased risk of heart attackand stroke compared with people with normal weight. Differentiation ofpreadipocytes to adipocytes requires actions of transcription regulatory networks.S100A16is a member of S100protein super family that carries calcium-bindingEF-hand motifs. Its expression is ubiquitous and elevated in various types of tumors.Using3T3-L1preadipocyte model, S100A16transgenic mouse and knock outmouse modle, and MEFs cell modle, we investigated the expression and function ofS100A16during differentiation into adipocytes as well as the potential roles ofS100A16in the regulation of insulin sensitivity.We found that the expression of S100A16was increased during differentiation,and overexpression of S100A16in3T3-L1preadipocytes increased their proliferationand markedly enhanced adipogenesis, but resulted in significant reduction ofinsulin-stimulated glucose uptake and phosphoryltion of AKT. In contrast,suppression of S100A16expression with RNAi significantly inhibited adipogensisand preadipocyte proliferation. Immunoprecipitation analysis revealed that S100A16could physically interact with p53, also a known inhibitor of adipogenesis.Thus, we reveal for the first time that S100A16protein is a noveladipogenesis-promoting factor, and that increased expression of S100A16inadipocytes can have a negative impact on insulin sensitivity.