title: Regulation of bile acid homeostasis by the intestinal Diet1-FGF15/19 axis.
abstract: OBJECTIVE
  Hepatic bile acid synthesis is controlled, in part, by a complex enterohepatic feedback regulatory mechanism. In this review, we focus on the role of the intestinal FGF15/19 hormone in modulating bile acid levels, and additional metabolic effects on glucose metabolism, nonalcoholic liver disease (NAFLD), and liver regeneration. We also highlight the newly identified intestinal protein, Diet1, which is a modulator of FGF15/19 levels.
  
  
  RESULTS
  Low FGF19 levels are associated with bile acid diarrhea and NAFLD. In contrast, high FGF19 levels are associated with diabetes remission following Roux-en-Y gastric bypass surgery, suggesting new therapeutic approaches against type 2 diabetes. The effect of FGF15/19 on liver plasticity is a double-edged sword: whereas elevated FGF15/19 levels improve survival of mice after partial hepatectomy, FGF19 mitogenic activity is associated with liver carcinoma. Finally, a recent study has identified Diet1, an intestinal factor that influences FGF15/19 levels in mouse intestine and human enterocytes. Diet1 represents the first factor shown to influence FGF15/19 levels at a post-transcriptional level.
  
  
  CONCLUSIONS
  The biological effects of FGF15/19 make it an attractive target for treating metabolic dysregulation underlying conditions such as fatty liver and type 2 diabetes. Further elucidation of the role of Diet1 in FGF15/19 secretion may provide a control point for the pharmacological modulation of FGF15/19 levels.
authors.affiliation: aDepartment of Human Genetics bDepartment of Medicine, David Geffen School of Medicine at UCLA cMolecular Biology Institute, University of California, Los Angeles, California, USA.
authors.forename: Karen
authors.initials: K
authors.lastname: Reue
authors.forename: Jessica M
authors.initials: JM
authors.lastname: Lee
authors.forename: Laurent
authors.initials: L
authors.lastname: Vergnes
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism*; D002352:Carrier Proteins / Q000378:metabolism*; D005346:Fibroblast Growth Factors / Q000378:metabolism*; D006706:Homeostasis; D006801:Humans; D007413:Intestinal Mucosa / Q000378:metabolism*; D008099:Liver / Q000378:metabolism
chemical_list: D001647:Bile Acids and Salts; D002352:Carrier Proteins; D005346:Fibroblast Growth Factors