Document Detail


Specific bile acids inhibit hepatic fatty acid uptake in mice.
MedLine Citation:
PMID:  22531947     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Comparative Study; Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Hepatology (Baltimore, Md.)     Volume:  56     ISSN:  1527-3350     ISO Abbreviation:  Hepatology     Publication Date:  2012 Oct 
Date Detail:
Created Date:  2012-10-05     Completed Date:  2013-01-17     Revised Date:  2013-10-17    
Medline Journal Info:
Nlm Unique ID:  8302946     Medline TA:  Hepatology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  1300-10     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 American Association for the Study of Liver Diseases.
Affiliation:
Department of Nutritional Science and Toxicology, University of California Berkeley, Berkeley, CA 94720-3104, USA.
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MeSH Terms
Descriptor/Qualifier:
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:
DK089202/DK/NIDDK NIH HHS; P30DK026743/DK/NIDDK NIH HHS; R01 DK066336/DK/NIDDK NIH HHS; R01 DK089202/DK/NIDDK NIH HHS; R01DK066336/DK/NIDDK NIH HHS; R56 DK066336/DK/NIDDK NIH HHS; R56DK066336/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
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
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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