Mechanisms Underlying the Pathogenesis of Non-alcoholic Fatty Liver Disease

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Project Summary Project Summary: Non-alcoholic fatty liver disease (NAFLD) is one of the most common chronic liver diseases worldwide. The pathogenic mechanism remains incompletely understood. Bile acids (BAs) are endocrine hormones that are important for the biological processes. Dysregulation of BA metabolism may cause cholestasis, liver cancer, NAFLD, etc. Activation of BA receptors FXR and TGR5 has been shown to protect against NAFLD in mice and clinical trials. Transmembrane protein 141 (TMEM141) belongs to the TMEM protein family that consists of proteins of mostly unknown functions. So far, nothing is known about the biological functions of TMEM141. In this project, we plan to investigate the role of hepatic TMEM141 in the pathogenesis of NAFLD. We will investigate whether and how hepatic TMEM141 regulates the development of NAFLD and bile acid metabolism, and how hepatic TMEM141 expression is regulated in NAFLD. We will use a number of genetically modified mice and a complementary approach to accomplish our goals.