1. Specific bile acids inhibit hepatic fatty acid uptake in mice
- Author
-
Barry M. Forman, Heather Tran, Andreas Stahl, Hyo Min Park, Robin Lai, Yuli Chen, Su Jin Song, Amy Helene Henkin, Chris Her, Jacquelyn J. Maher, Biao Nie, Min Lin, Melissa Kazantzis, and Stephanie M. Ng
- Subjects
Inbred Strains ,Medical Biochemistry and Metabolomics ,Oral and gastrointestinal ,chemistry.chemical_compound ,Mice ,Random Allocation ,2.1 Biological and endogenous factors ,Aetiology ,Cells, Cultured ,chemistry.chemical_classification ,Cultured ,Bile acid ,Subcutaneous ,Liver Disease ,Deoxycholic acid ,Fatty liver ,Ursodeoxycholic Acid ,Fatty Acids ,Fatty Acid Transport Proteins ,G protein-coupled bile acid receptor ,Ursodeoxycholic acid ,Biochemistry ,Lithocholic Acid ,medicine.drug ,Deoxycholic Acid ,medicine.drug_class ,Injections, Subcutaneous ,Cells ,Chronic Liver Disease and Cirrhosis ,Clinical Sciences ,Immunology ,Mice, Inbred Strains ,Biology ,Real-Time Polymerase Chain Reaction ,Sensitivity and Specificity ,Article ,Injections ,Bile Acids and Salts ,medicine ,Animals ,Humans ,Metabolic and endocrine ,Nutrition ,Hepatology ,Triglyceride ,Gastroenterology & Hepatology ,Animal ,Fatty acid ,Metabolism ,medicine.disease ,Lipid Metabolism ,Disease Models, Animal ,chemistry ,Disease Models ,Hepatocytes ,Digestive Diseases - Abstract
UnlabelledBile 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%.ConclusionThe 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.
- Published
- 2012