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Specific bile acids inhibit hepatic fatty acid uptake in mice
Author(s) -
Nie Biao,
Park Hyo Min,
Kazantzis Melissa,
Lin Min,
Henkin Amy,
Ng Stephanie,
Song Sujin,
Chen Yuli,
Tran Heather,
Lai Robin,
Her Chris,
Maher Jacquelyn J.,
Forman Barry M.,
Stahl Andreas
Publication year - 2012
Publication title -
hepatology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.488
H-Index - 361
eISSN - 1527-3350
pISSN - 0270-9139
DOI - 10.1002/hep.25797
Subject(s) - ursodeoxycholic acid , bile acid , deoxycholic acid , biochemistry , triglyceride , metabolism , in vivo , fatty acid , chemistry , biology , medicine , cholesterol , microbiology and biotechnology
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. (H EPATOLOGY 2012)