Zhou Huiping, Hylemon Phillip B
Department of Microbiology and Immunology, Virginia Commonwealth University, Medical College of Virginia Campus, Richmond, VA 23298, United States; McGuire VA Medical Center, Richmond, VA 23249, United States.
Steroids. 2014 Aug;86:62-8. doi: 10.1016/j.steroids.2014.04.016. Epub 2014 May 10.
Bile salts play crucial roles in allowing the gastrointestinal system to digest, transport and metabolize nutrients. They function as nutrient signaling hormones by activating specific nuclear receptors (FXR, PXR, Vitamin D) and G-protein coupled receptors [TGR5, sphingosine-1 phosphate receptor 2 (S1PR2), muscarinic receptors]. Bile acids and insulin appear to collaborate in regulating the metabolism of nutrients in the liver. They both activate the AKT and ERK1/2 signaling pathways. Bile acid induction of the FXR-α target gene, small heterodimer partner (SHP), is highly dependent on the activation PKCζ, a branch of the insulin signaling pathway. SHP is an important regulator of glucose and lipid metabolism in the liver. One might hypothesize that chronic low grade inflammation which is associated with insulin resistance, may inhibit bile acid signaling and disrupt lipid metabolism. The disruption of these signaling pathways may increase the risk of fatty liver and non-alcoholic fatty liver disease (NAFLD). Finally, conjugated bile acids appear to promote cholangiocarcinoma growth via the activation of S1PR2.
胆汁盐在使胃肠系统消化、运输和代谢营养物质方面发挥着关键作用。它们通过激活特定的核受体（法尼醇X受体、孕烷X受体、维生素D）和G蛋白偶联受体[G蛋白偶联胆汁酸受体5、鞘氨醇-1-磷酸受体2（S1PR2）、毒蕈碱受体]，作为营养信号激素发挥作用。胆汁酸和胰岛素似乎在调节肝脏中营养物质的代谢方面相互协作。它们都激活AKT和ERK1/2信号通路。胆汁酸诱导法尼醇X受体α靶基因小异二聚体伴侣（SHP）高度依赖于蛋白激酶Cζ的激活，蛋白激酶Cζ是胰岛素信号通路的一个分支。SHP是肝脏中葡萄糖和脂质代谢的重要调节因子。有人可能会推测，与胰岛素抵抗相关的慢性低度炎症可能会抑制胆汁酸信号传导并扰乱脂质代谢。这些信号通路的破坏可能会增加患脂肪肝和非酒精性脂肪性肝病（NAFLD）的风险。最后，结合胆汁酸似乎通过激活S1PR2促进胆管癌生长。
