title: Specific bile acids inhibit hepatic fatty acid uptake in mice.
abstract: Bile acids are known to play important roles as detergents in the absorption of hydrophobic nutrients and as signaling molecules in the regulation of metabolism. We tested the novel hypothesis that naturally occurring bile acids interfere with protein-mediated hepatic long chain free fatty acid (LCFA) uptake. To this end, stable cell lines expressing fatty acid transporters as well as primary hepatocytes from mouse and human livers were incubated with primary and secondary bile acids to determine their effects on LCFA uptake rates. We identified ursodeoxycholic acid (UDCA) and deoxycholic acid (DCA) as the two most potent inhibitors of the liver-specific fatty acid transport protein 5 (FATP5). Both UDCA and DCA were able to inhibit LCFA uptake by primary hepatocytes in a FATP5-dependent manner. Subsequently, mice were treated with these secondary bile acids in vivo to assess their ability to inhibit diet-induced hepatic triglyceride accumulation. Administration of DCA in vivo via injection or as part of a high-fat diet significantly inhibited hepatic fatty acid uptake and reduced liver triglycerides by more than 50%.
  
  
  CONCLUSIONS
  The data demonstrate a novel role for specific bile acids, and the secondary bile acid DCA in particular, in the regulation of hepatic LCFA uptake. The results illuminate a previously unappreciated means by which specific bile acids, such as UDCA and DCA, can impact hepatic triglyceride metabolism and may lead to novel approaches to combat obesity-associated fatty liver disease.
authors.affiliation: Department of Nutritional Science and Toxicology, University of California Berkeley, Berkeley, CA 94720-3104, USA.
authors.forename: Biao
authors.initials: B
authors.lastname: Nie
authors.forename: Hyo Min
authors.initials: HM
authors.lastname: Park
authors.forename: Melissa
authors.initials: M
authors.lastname: Kazantzis
authors.forename: Min
authors.initials: M
authors.lastname: Lin
authors.forename: Amy
authors.initials: A
authors.lastname: Henkin
authors.forename: Stephanie
authors.initials: S
authors.lastname: Ng
authors.forename: Sujin
authors.initials: S
authors.lastname: Song
authors.forename: Yuli
authors.initials: Y
authors.lastname: Chen
authors.forename: Heather
authors.initials: H
authors.lastname: Tran
authors.forename: Robin
authors.initials: R
authors.lastname: Lai
authors.forename: Chris
authors.initials: C
authors.lastname: Her
authors.forename: Jacquelyn J
authors.initials: JJ
authors.lastname: Maher
authors.forename: Barry M
authors.initials: BM
authors.lastname: Forman
authors.forename: Andreas
authors.initials: A
authors.lastname: Stahl
mesh_terms: D000818:Animals; D001647:Bile Acids and Salts / Q000378:metabolism; D002478:Cells, Cultured; D003840:Deoxycholic Acid / Q000378:metabolism / Q000494:pharmacology; D004195:Disease Models, Animal; D050612:Fatty Acid Transport Proteins / Q000187:drug effects / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism*; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007279:Injections, Subcutaneous; D050356:Lipid Metabolism / Q000187:drug effects; D008095:Lithocholic Acid / Q000378:metabolism / Q000494:pharmacology*; D051379:Mice; D008815:Mice, Inbred Strains; D011897:Random Allocation; D060888:Real-Time Polymerase Chain Reaction; D012680:Sensitivity and Specificity; D014580:Ursodeoxycholic Acid / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D001647:Bile Acids and Salts; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; C113098:Slc27a5 protein, mouse; D003840:Deoxycholic Acid; D008095:Lithocholic Acid; D014580:Ursodeoxycholic Acid