Nuclear Receptor-Dependent Bile Acid Signaling Is Required for Normal Liver Regeneration

• DOI: 10.1126/science.1121435
• Publication Date: 2006-04-13T21:12:35Z
• Authors: Wendong Huang; Ke Ma; Jun Zhang; Mohammed Qatanani; James Cuvillier; Jun Liu; Bingning Dong; Xiongfei Huang; David D. Moore
• Keywords: DNA Replication; 0301 basic medicine; Cholestyramine Resin; Forkhead Box Protein M1; Genes, myc; Cell Count; Forkhead Transcription Factors; Cholic Acid; Diet; Liver Regeneration; Bile Acids and Salts; DNA-Binding Proteins; 03 medical and health sciences; Gene Expression Regulation; Liver; Hepatocytes; Animals; Cytokines; Hepatectomy; Homeostasis; Cholesterol 7-alpha-Hydroxylase; Growth Substances

Liver mass depends on one or more unidentified humoral signals that drive regeneration when liver functional capacity is diminished. Bile acids are important liver products, and their levels are tightly regulated. Here, we identify a role for nuclear receptor–dependent bile acid signaling in normal liver regeneration. Elevated bile acid levels accelerate regeneration, and decreased levels inhibit liver regrowth, as does the absence of the primary nuclear bile acid receptor FXR. We propose that FXR activation by increased bile acid flux is a signal of decreased functional capacity of the liver. FXR, and possibly other nuclear receptors, may promote homeostasis not only by regulating expression of appropriate metabolic target genes but also by driving homeotrophic liver growth.