Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Jiangsu Key Laboratory of Drug Screening, China Pharmaceutical University, Nanjing 210009, China.
Pharmacol Ther. 2018 Oct;190:81-90. doi: 10.1016/j.pharmthera.2018.04.005. Epub 2018 Apr 22.
Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat deposition in the liver in the absence of significant alcohol consumption. Dysregulated bile acid (BA) metabolism is an important indicator in the pathology of NAFLD, which could progress into more severe forms of liver injury. Lipid metabolism, immune environment and intestinal bacteria are all affected by dysregulated BA metabolism directly, but the mechanisms remain unclear. Several drug candidates that target BA metabolism, either used alone or in combination with other agents, are currently under development for treatment of NAFLD. Here, we summarize the relationship of dysregulated BA metabolism and NAFLD, discuss the effects and mechanisms of dysregulated BAs-induced lipid metabolism disorder. Challenges in developing novel treatments are also discussed.
非酒精性脂肪性肝病(NAFLD)的特征是在没有明显饮酒的情况下肝脏内脂肪沉积过多。胆汁酸(BA)代谢失调是 NAFLD 病理学中的一个重要指标,它可能进展为更严重的肝损伤。脂质代谢、免疫环境和肠道细菌都直接受到 BA 代谢失调的影响,但具体机制尚不清楚。目前有几种针对 BA 代谢的药物候选物正在开发中,无论是单独使用还是与其他药物联合使用,都可用于治疗 NAFLD。在这里,我们总结了 BA 代谢失调与 NAFLD 的关系,讨论了 BA 代谢失调诱导的脂质代谢紊乱的作用和机制。还讨论了开发新型治疗方法所面临的挑战。