125I Radioimmunoassay of serum ursodeoxycholyl conjugates

Hill, Alexander J.; Ross, P. E.; Bouchier, I. A. D.

doi:10.1016/0009-8981(83)90159-6

Cited by 9 publications

(1 citation statement)

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“…Although passage through the enterohepatic circulation can lead to reconjugation and bioconversion, we expect that with chronic administration of DCA or UDCA, we can establish a mix of conjugated and unconjugated bile acids. Indeed, this has been shown for UDCA treatment in gallstone patients39 and, importantly, feeding of DCA‐ and UDCA‐supplemented diets has been shown to increase levels of both conjugated as well as unconjugated forms of these bile acids 40. Oral administration of UDCA can also raise circulating UDCA levels to over 17 μM,41 which is well above the observed IC 50 for FATP5.…”

Section: Discussionmentioning

confidence: 80%

Specific bile acids inhibit hepatic fatty acid uptake in mice

et al. 2012

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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. Here 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%. In summary, 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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Section: Discussionmentioning

confidence: 80%