FXR activation protects against NAFLD via bile-acid-dependent reductions in lipid absorption

• Published in: Cell metabolism Vol. 33; no. 8; pp. 1671 - 1684.e4
• Main Authors: Clifford, Bethan L., Sedgeman, Leslie R., Williams, Kevin J., Morand, Pauline, Cheng, Angela, Jarrett, Kelsey E., Chan, Alvin P., Brearley-Sholto, Madelaine C., Wahlström, Annika, Ashby, Julianne W., Barshop, William, Wohlschlegel, James, Calkin, Anna C., Liu, Yingying, Thorell, Anders, Meikle, Peter J., Drew, Brian G., Mack, Julia J., Marschall, Hanns-Ulrich, Tarling, Elizabeth J., Edwards, Peter A., de Aguiar Vallim, Thomas Q.
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 03.08.2021
• Subjects: Animals; beta-muricholic acid; Bile; bile acids; Bile Acids and Salts - metabolism; binding; Cell Biology; cholesterol; Endocrinology & Metabolism; Endocrinology and Diabetes; Endokrinologi och diabetes; farnesoid-x-receptor; fatty liver-disease; FXR; Humans; intestinal lipid absorption; Lipids; Liver - metabolism; metabolism; Mice; Mice, Inbred C57BL; NAFLD; Non-alcoholic Fatty Liver Disease - metabolism; Non-alcoholic Fatty Liver Disease - prevention & control; nuclear receptor; Phosphatidate Phosphatase - metabolism; Receptors, Cytoplasmic and Nuclear - metabolism; small heterodimer partner; intestinal lipid absorption; FXR; NAFLD; bile acids

FXR agonists are used to treat non-alcoholic fatty liver disease (NAFLD), in part because they reduce hepatic lipids. Here, we show that FXR activation with the FXR agonist GSK2324 controls hepatic lipids via reduced absorption and selective decreases in fatty acid synthesis. Using comprehensive lip...