Bile Acid Receptors and the Gut–Liver Axis in Nonalcoholic Fatty Liver Disease
Rui Xue,
Lianyong Su,
Shengyi Lai,
Yanyan Wang,
Derrick Zhao,
Jiangao Fan,
Weidong Chen,
Phillip B. Hylemon,
Huiping Zhou
Affiliations
Rui Xue
Department of Gastroenterology, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 210092, China
Lianyong Su
Department of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23284, USA
Shengyi Lai
Department of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23284, USA
Yanyan Wang
School of Pharmaceutical Science, Anhui University of Chinese Medicine, Hefei 230031, China
Derrick Zhao
Department of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23284, USA
Jiangao Fan
Department of Gastroenterology, Shanghai Key Lab of Pediatric Gastroenterology and Nutrition, Shanghai 210092, China
Weidong Chen
School of Pharmaceutical Science, Anhui University of Chinese Medicine, Hefei 230031, China
Phillip B. Hylemon
Department of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23284, USA
Huiping Zhou
Department of Microbiology and Immunology, Medical College of Virginia and McGuire Veterans Affairs Medical Center, Virginia Commonwealth University, Richmond, VA 23284, USA
The prevalence of nonalcoholic fatty liver disease (NAFLD) has been significantly increased due to the global epidemic of obesity. The disease progression from simple steatosis (NAFL) to nonalcoholic steatohepatitis (NASH) is closely linked to inflammation, insulin resistance, and dysbiosis. Although extensive efforts have been aimed at elucidating the pathological mechanisms of NAFLD disease progression, current understanding remains incomplete, and no effective therapy is available. Bile acids (BAs) are not only important physiological detergents for the absorption of lipid-soluble nutrients in the intestine but also metabolic regulators. During the last two decades, BAs have been identified as important signaling molecules involved in lipid, glucose, and energy metabolism. Dysregulation of BA homeostasis has been associated with NAFLD disease severity. Identification of nuclear receptors and G-protein-coupled receptors activated by different BAs not only significantly expanded the current understanding of NAFLD/NASH disease progression but also provided the opportunity to develop potential therapeutics for NAFLD/NASH. In this review, we will summarize the recent studies with a focus on BA-mediated signaling pathways in NAFLD/NASH. Furthermore, the therapeutic implications of targeting BA-mediated signaling pathways for NAFLD will also be discussed.