Department of Pharmacology, Toxicology, and Therapeutics, University of Kansas Medical Center, Kansas City, Kansas, United States of America.
PLoS One. 2012;7(3):e32551. doi: 10.1371/journal.pone.0032551. Epub 2012 Mar 5.
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.
衰老是一个渐进的过程，身体的适应和功能能力逐渐下降。胆汁酸（BAs）已被认为是调节葡萄糖、脂质和能量体内平衡的信号分子。本研究通过超高效液相色谱-串联质谱（UPLC-MS/MS）在 3 至 27 个月龄的雄性和雌性 C57BL/6 小鼠的血清和肝脏中描述了个体 BA 浓度的年龄相关性变化。在雌性小鼠中，血清中总 BA 浓度从 3 个月增加到 27 个月增加了 340%，而在雄性小鼠中，它们的年龄相对稳定。在衰老过程中，雄性和雌性小鼠有以下共同变化：（1）肝脏中 BA 浓度相对稳定；（2）3 至 27 个月血清和肝脏中β-鼠胆酸（βMCA）的比例增加，脱氧胆酸（DCA）减少；（3）3 至 27 个月血清和肝脏中总 BA 变得更加亲水。在雌性小鼠中，（1）肝脏 BA 摄取转运蛋白的 mRNA，即 Na(+)/牛磺胆酸钠共转运多肽（Ntcp）和有机阴离子转运蛋白 1b2（Oatp1b2），在 12 个月后减少，其蛋白质也有类似的趋势；（2）BA 合成的限速酶胆固醇 7α-羟化酶（Cyp7a1）的 mRNA 从 3 个月增加到 9 个月，此后一直保持较高水平。然而，在雄性小鼠中，Ntcp、Oatp1b2 和 Cyp7a1 的 mRNA 随年龄变化相对稳定。综上所述，本研究表明，在衰老过程中，雄性和雌性小鼠血清和肝脏中的 BA 浓度和组成呈现性别差异，这可能是由于 BA 转运蛋白 Ntcp 和 Oatp1b2 以及合成酶 Cyp7a1 的性别差异表达所致。
