Area of Research: Diabetes, Adipose tissue, Nuclear receptor, Physiology, mice, adipocyte differentiation, Wnt signaling, primary cells (MEFs, preadipocytes and 3T3L1), Lung cells (E86, A549), Lung Cancer.

 
Area of Research :

Diabetes, Adipose tissue, Nuclear receptor, Physiology, mice, adipocyte differentiation, Wnt signaling, primary cells (MEFs, preadipocytes and 3T3L1), Lung cells (E86, A549), Lung Cancer

Title of the PhD Thesis: The Farnesoid X Receptor regulates adipocyte differentiation and function by promoting the Peroxisome Proliferator-Activated Receptor-gamma and interfering with the Wnt/Beta-catenin pathway
 

Brief Outline of the PhD Thesis:

Although the bile acid nuclear receptor Farnesoid X Receptor (FXR) is expressed in adipose tissue, its function is ill-defined. PPARgamma is a master controller of adipocyte differentiation and function. The aim of this study was to analyse the role of FXR KO in adipocyte function and to assess whether it modulates PPARgamma action. Therefore, we tested the -responsiveness of FXR mice and cells to the PPARgamma activator rosiglitazone. Our results show that obese FXR KO  mice display a resistance to rosiglitazone treatment. In vitro, rosiglitazone treatment did not induce normal adipocyte differentiation and lipid droplet formation in FXR KO mouse embryonic fibroblasts (MEFs) and preadipocytes. Moreover, FXR-/- MEFs display an increased lipolysis and decreased de novo lipogenesis, resulting in reduced intracellular triglyceride content, even when PPARgamma is activated. Retroviral-mediated FXR re-expression in FXR KO MEFs restored the induction of the adipogenic marker genes during adipocyte differentiation induced with rosiglitazone. The expression of Wnt/Beta-catenin pathway and target genes was increased in FXR KO adipose tissue and MEFs. Moreover, the expression of several endogenous inhibitors of this pathway was decreased early during the adipocyte differentiation of FXR KO MEFs. These findings demonstrate that FXR regulates adipocyte differentiation and function by regulating two opposite pathways of adipocyte differentiation, the PPARgamma and Wnt/Beta-catenin pathways