Loss of STAT5 in adipocytes increases subcutaneous fat mass via sex-dependent and depot-specific pathways

The STAT (Signal Transducers and Activators of Transcription) family of transcription factors contributes to adipocyte development and function. STAT5A and STAT5B are induced during adipocyte differentiation and are primarily activated by growth hormone (GH). Studies in mice lacking adipocyte GH receptor or STAT5 support their roles in lipolysis-mediated reduction of adipose tissue mass. We have generated a mouse model lacking both STAT5 genes specifically in adipocytes (STAT5AKO). Notably, both sexes of STAT5AKO mice have increased inguinal adipose tissue without any changes in gonadal fat mass. However, both depots exhibit substantial differences in fat cell size. Study of STAT5AKO mice also have revealed that GHs ability to induce insulin resistance is dependent upon STAT5 in adipocytes, but its ability to reduce adipose tissue mass is STAT5 independent. Additional observations, which were not predicted, indicate that the causes and regulation of increased fat mass in STAT5AKO mice are sex- and depot-dependent.