화학공학소재연구정보센터
Biochemical and Biophysical Research Communications, Vol.527, No.1, 49-55, 2020
Promotion of lipogenesis by PPAR gamma-activated FXR expression in adipocytes
Farnesoid X receptor (FXR), a bile acid receptor, is known to be involved in the promotion of adipogenesis. However, the regulation mechanism of FXR-promoted adipogenesis remains unclear. In this study, we investigated the regulation mechanism of FXR-mediated activation of adipogenesis in murine adipocyte 3T3-L1 cells. Chenodeoxycholic acid (CDCA), a potent FXR agonist, enhanced the accumulation of intracellular triglycerides and the expression of the adipogenic and lipogenic genes, while guggulsterone, an FXR antagonist, suppressed CDCA-activated adipogenesis. Moreover, troglitazone, a peroxisome proliferator-activated receptor (PPAR) gamma agonist, elevated the expression of the FXR gene during adipogenesis, similar to that of the PPAR gamma gene. Chromatin immunoprecipitation assay demonstrated that PPAR gamma bound to the PPAR-responsive element of the FXR gene in a PPAR gamma agonist-dependent manner. Furthermore, FXR activation induced the expression of the stearoyl-CoA desaturase (SCD) gene in adipocytes. The FXR-response element (FXRE) was found in the SCD gene promoter, and FXR bound to the FXRE of the SCD gene promoter, and its binding efficiency was enhanced by CDCA in adipocytes. These results indicate that FXR assisted lipogenesis through the enhanced expression of SCD in a PPAR gamma-dependent manner in adipocytes, making this study the first to identify the role of FXR in the promotion of lipogenesis by PPAR gamma activation. (c) 2020 Elsevier Inc. All rights reserved.