Curr Opin Lipidol. 2019 Jun;30(3):244-254. doi: 10.1097/MOL.0000000000000597.
The purpose of this review is to discuss the influence of obesity, insulin resistance, type 2 diabetes (T2D), and nonalcoholic fatty liver disease (NAFLD) on bile acid metabolism and to analyze whether these findings reinforce current beliefs about the role of bile acids in the pathophysiology of these diseases.
Discordant results on plasma bile acid alterations in NAFLD patients have been reported. Obesity, insulin resistance, and T2D, common comorbidities of NAFLD, have been associated with bile acid changes, but the individual bile acid species variations differ between studies (summarized in this review), perhaps because of clinicobiological differences between the studied patient populations and the heterogeneity of statistical analyses applied.
The regulatory role of bile acids in metabolic and cellular homeostasis renders bile acids attractive candidates as players in the pathophysiology of NAFLD. However, considering the complex relationship between NAFLD, obesity, insulin resistance and T2D, it is difficult to establish clear and independent associations between bile acid alterations and these individual diseases. Though bile acid alterations may not drive NAFLD progression, signaling pathways activated by bile acids remain potent therapeutic targets for its treatment. Further studies with appropriate matching or adjustment for potential confounding factors are necessary to determine which pathophysiological conditions drive the alterations in bile acid metabolism.
本文旨在讨论肥胖、胰岛素抵抗、2 型糖尿病（T2D）和非酒精性脂肪性肝病（NAFLD）对胆汁酸代谢的影响，并分析这些发现是否支持当前关于胆汁酸在这些疾病病理生理学中作用的观点。
NAFLD 患者的血浆胆汁酸变化存在不一致的结果。肥胖、胰岛素抵抗和 T2D 是 NAFLD 的常见合并症，与胆汁酸变化有关，但不同研究之间的个体胆汁酸种类变化不同（本文综述总结），这可能是由于研究人群的临床生物学差异和应用的统计分析的异质性所致。
胆汁酸在代谢和细胞内稳态中的调节作用使胆汁酸成为 NAFLD 病理生理学的有吸引力的候选因子。然而，考虑到 NAFLD、肥胖、胰岛素抵抗和 T2D 之间的复杂关系，很难在这些单独的疾病之间建立胆汁酸改变与这些疾病之间的明确和独立的关联。尽管胆汁酸改变可能不会导致 NAFLD 的进展，但胆汁酸激活的信号通路仍然是其治疗的有效治疗靶点。需要进一步的研究，以适当匹配或调整潜在的混杂因素，以确定哪些病理生理条件导致胆汁酸代谢的改变。
