The Transcription Factor ETV5 Regulates Adipogenesis through PPARg Signaling Pathway

Abstract

ETV5 is a member of PEA3 subfamily of E26 transformation-specific (ETS) transcription factors, characterized by the conserved DNA binding domain, ETS domain. Recently, a series of genomic-wide association studies (GWAS) found that ETV5 is associated with obesity. ETV5 knockout mice have lower fat mass and resistant to diet induced obesity, suggesting it was involved in the adipogenesis. In our study, we showed that ETV5 was expressed in the nucleus of adipocyte. Its expression level was altered according to different nutrient status. In order to exclude other tissues’ effect, we examine its biological function in preadipocyte 3T3-L1 cells. We found that the protein level but not the mRNA level of ETV5 was significantly elevated during adipogenesis. We utilized lentivirus to successfully knockdown ETV5 in 3T3-L1 cells. Deficiency of ETV5 resulted in reduced number and smaller size of adipocytes showed by oil red O staining. The major genetic changes involved in the impaired adipogenesis was defective PPAR signaling. Rosiglitazone stimulation of 3T3-L1 could restore adipogenesis caused by ETV5 deficiency. Dual luciferase assay found that ETV5 potently enhanced PPRE activity. These results suggest ETV5 is an important regulator of adipogenesis in early stage and a potential target for the treatment of obesity. Disclosure Z. Mao: None.