Excess glucocorticoid (GC) signaling in adipose tissue is a key driver of insulin resistance and hepatic steatosis, but underlying mechanisms have not been fully elucidated. Signal transducer and activator of transcription 5 (STAT5) signaling in adipocytes has also been implicated in the progression of similar metabolic disturbances. Although STAT5 has been shown to interact with the glucocorticoid receptor (GR) in many cell types including adipocytes, the relevance of the STAT5/GR complex has not been investigated in adipocytes. Adult male and female adipocyte-specific STAT5 knockout (STAT5AKO) and floxed mice were given corticosterone (CORT) or vehicle in their drinking water for 1 wk and examined for differences in their metabolic responses to GC excess. CORT-induced lipolysis, insulin resistance, and changes in body composition were comparable between genotypes and in both sexes. Adipocyte STAT5 is not necessary for GC-mediated progression of metabolic disease.NEW & NOTEWORTHY Both STAT5 and glucocorticoid receptor contribute to metabolic processes and type 2 diabetes, in large part, due to their functions in adipocytes. These two transcription factors can form a complex and function together. Our novel studies determined the role of adipocyte STAT5 in glucocorticoid-induced diabetes. We observed that STAT5 in adipocytes is not needed for glucocorticoid-induced diabetes.
Keywords: adipose tissue; glucocorticoids; hepatic steatosis; insulin resistance; lipolysis.