| Specific bile acids inhibit hepatic fatty acid uptake in mice. | |
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MedLine Citation:
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PMID: 22531947 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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%. Conclusion: 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. |
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Authors:
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Biao Nie; Hyo Min Park; Melissa Kazantzis; Min Lin; Amy Henkin; Stephanie Ng; Sujin Song; Yuli Chen; Heather Tran; Robin Lai; Chris Her; Jacquelyn J Maher; Barry M Forman; Andreas Stahl |
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Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Hepatology (Baltimore, Md.) Volume: 56 ISSN: 1527-3350 ISO Abbreviation: Hepatology Publication Date: 2012 Oct |
Date Detail:
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Created Date: 2012-10-05 Completed Date: 2013-01-17 Revised Date: 2013-04-16 |
Medline Journal Info:
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Nlm Unique ID: 8302946 Medline TA: Hepatology Country: United States |
Other Details:
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Languages: eng Pagination: 1300-10 Citation Subset: IM |
Copyright Information:
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Copyright © 2012 American Association for the Study of Liver Diseases. |
Affiliation:
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Department of Nutritional Science and Toxicology, University of California Berkeley, Berkeley, CA 94720-3104, USA. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Animals Bile Acids and Salts / metabolism Cells, Cultured Deoxycholic Acid / metabolism, pharmacology Disease Models, Animal Fatty Acid Transport Proteins / drug effects, metabolism* Fatty Acids / metabolism* Hepatocytes / drug effects, metabolism Humans Injections, Subcutaneous Lipid Metabolism / drug effects Lithocholic Acid / metabolism, pharmacology* Mice Mice, Inbred Strains Random Allocation Real-Time Polymerase Chain Reaction Sensitivity and Specificity Ursodeoxycholic Acid / metabolism, pharmacology* |
| Grant Support | |
ID/Acronym/Agency:
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DK089202/DK/NIDDK NIH HHS; P30DK026743/DK/NIDDK NIH HHS; R01DK066336/DK/NIDDK NIH HHS; R56DK066336/DK/NIDDK NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Bile Acids and Salts; 0/Fatty Acid Transport Proteins; 0/Fatty Acids; 0/Slc27a5 protein, mouse; 128-13-2/Ursodeoxycholic Acid; 434-13-9/Lithocholic Acid; 83-44-3/Deoxycholic Acid |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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