Constitutively active Stat5A and Stat5B promote adipogenesis

Abstract

Objective The metabolic syndrome is an important social problem affecting many people in developed countries. Obesity is a leading cause of this syndrome, hence understanding molecular mechanisms underlying obesity is of prime importance for preventive medicine to develop novel methods to alleviate the corresponding social cost as well as for pharmaceutical companies to develop antimetabolic drugs. Methods Since adipocytes play an important role in obesity, we explored the signaling pathways leading to differentiation of adipocytes. We used a preadipocyte cell line to monitor the differentiation of adipocytes, and virusmediated gene transfer to assess the role of the transcription factor Stat5 in adipogenesis. Adipocyte differentiation was assessed by Northern blot and Western blot analyses as well as accumulation of fat droplets in cells. Promoter activity of the proadipogenic transcription factor peroxisome proliferator-activated receptor-gamma (PPARc) was evaluated by luciferase assay. Results Virus-mediated gene transfer of the constitutively active form of both Stat5A and Stat5B resulted in enhanced adipocyte differentiation in the absence of fetal bovine serum (FBS) as judged by expression of proadipogenic factors as well as accumulation of fat droplets in cells. Such a proadipogenic effect of Stat5 is, in part, mediated by its ability to enhance transcription of PPARc a master transcriptional regulator in adipogenesis. Conclusion The constitutively active form of Stat5A and Stat5B promoted adipocyte differentiation in the absence of FBS via induction of PPARc. © The Japanese Society for Hygiene 2011.