Abstract
Aging is a physiological process with a progressive decline of adaptation and functional capacity of the body. Bile acids (BAs) have been recognized as signaling molecules regulating the homeostasis of glucose, lipid, and energy. The current study characterizes the age-related changes of individual BA concentrations by ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) in serum and liver of male and female C57BL/6 mice from 3 to 27 months of age. Total BA concentrations in serum increased 340% from 3 to 27 months in female mice, whereas they remained relatively constant with age in male mice. During aging, male and female mice shared the following changes: (1) BA concentrations in liver remained relatively constant; (2) the proportions of beta-muricholic acid (βMCA) increased and deoxycholic acid (DCA) decreased between 3 and 27 months in serum and liver; and (3) total BAs in serum and liver became more hydrophilic between 3 and 27 months. In female mice, (1) the mRNAs of hepatic BA uptake transporters, the Na+/taurocholate cotransporting polypeptide (Ntcp) and the organic anion transporting polypeptide 1b2 (Oatp1b2), decreased after 12 months, and similar trends were observed for their proteins; (2) the mRNA of the rate-limiting enzyme for BA synthesis, cholesterol 7α-hydroxylase (Cyp7a1), increased from 3 to 9 months and remained high thereafter. However, in male mice, Ntcp, Oatp1b2, and Cyp7a1 mRNAs remained relatively constant with age. In summary, the current study shows gender-divergent profiles of BA concentrations and composition in serum and liver of mice during aging, which is likely due to the gender-divergent expression of BA transporters Ntcp and Oatp1b2 as well as the synthetic enzyme Cyp7a1.
Highlights
Aging has become one of the most important global issues, because the elderly population are increasing, and it is estimated they will reach 22% of the population in 2050
chenodeoxycholic acid (CDCA) can be hydroxylated into alpha-muricholic acid, which is converted to beta-muricholic acid by 7OH epimerization
CA is converted to its secondary bile acids (BAs) deoxycholic acid (DCA), CDCA to lithocholic acid (LCA) and ursodeoxycholic acid (UDCA), alpha-muricholic acid (aMCA) to murideoxycholic acid (MDCA), and beta-muricholic acid (bMCA) to v-muricholic acid and hyodeoxycholic acid (HDCA) [3,4]
Summary
Aging has become one of the most important global issues, because the elderly population (with chronological age of 65 years and older) are increasing, and it is estimated they will reach 22% of the population in 2050. Bile acids (BAs) play multifaceted physiological functions. Apart from their well-known roles for dietary lipid absorption and cholesterol homeostasis, BAs are increasingly appreciated as complex metabolic signaling molecules [2], regulating glucose, lipid, and energy metabolism. Primary BAs are synthesized in the liver, namely cholic acid (CA) and chenodeoxycholic acid (CDCA) in humans. Bacterial transformation of primary BAs occur to synthesize secondary BAs. CA is converted to its secondary BA deoxycholic acid (DCA), CDCA to lithocholic acid (LCA) and ursodeoxycholic acid (UDCA), aMCA to murideoxycholic acid (MDCA), and bMCA to v-muricholic acid (vMCA) and hyodeoxycholic acid (HDCA) [3,4]
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