Abstract

Intestinal and hepatic bile acid transporters are important for enterohepatic bile acid circulation and pharmacokinetics. Based on previous literature, we hypothesized that the expression of bile acid transporters and intestinal bile acid absorption are lower in older individuals. Here, we measured active taurocholate absorption across the ileum of male C57BL/6 mice in two different age cohorts – young (age range of 89–224 days) and old (age range of 613–953 days). Also examined in these mice were mRNA expression of the major bile acid transporters – Asbt and Ostα/β in the ileum, and Ntcp, Oatp1b2 and Bsep in the liver. Mean intestinal taurocholate absorption was significantly lower (~50%) in mice in the older cohort compared to those in the younger cohort. In the ileum, the expression of Asbt was significantly lower in the older cohort, but expression of Ostα/β was not affected by age. The lower capacity for intestinal bile acid absorption in the older animals is consistent with their lower expression level of Asbt. Of the hepatic bile acid transporters examined, expression of Ntcp and Oatp1b2 were significantly lower in the older mice. This is the first study to directly measure intestinal bile acid absorption as a function of age. The data suggest a lower capacity for intestinal bile acid absorption in older animals. Also, lower expression of Asbt, Ntcp, and Oatp1b2 in older individuals could influence pharmacokinetics of drug substrates.

Highlights

  • Bile acids are important for many physiological processes, such as the emulsification of dietary fats, and the regulation of glucose, lipid, and energy metabolism (Chiang 2013)

  • Intestinal bile acid absorption is accomplished in the ileum by the apical Na+-dependent bile acid transporter (ASBT) and the basolateral organic solute transporter a/ b (OSTa/b) (Pellicoro and Faber 2007)

  • We examined the mRNA expression of bile acid transporters in the ileum and liver of mice in the two cohorts

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Summary

Introduction

Bile acids are important for many physiological processes, such as the emulsification of dietary fats, and the regulation of glucose, lipid, and energy metabolism (Chiang 2013). Enterohepatic bile acid cycling involves the concerted activity of intestinal and hepatic bile acid transporters. Intestinal bile acid absorption is accomplished in the ileum by the apical Na+-dependent bile acid transporter (ASBT) and the basolateral organic solute transporter a/ b (OSTa/b) (Pellicoro and Faber 2007). This is a highly efficient process, in that ~95% of the intestinal bile acid load is absorbed by these transporters (Pellicoro and Faber 2007). Bile acid transporters are important for the intestinal absorption and hepatic elimination of small molecule drugs, and changes in their activity, with age for example, could influence oral bioavailability

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