Department of Physiology and Biophysics, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Division of Gastroenterology & Hepatology, Department of Medicine, College of Medicine, University of Illinois at Chicago, Chicago, Illinois, USA.
Compr Physiol. 2019 Dec 18;10(1):21-56. doi: 10.1002/cphy.c190007.
The intestinal reclamation of bile acids is crucial for the maintenance of their enterohepatic circulation. The majority of bile acids are actively absorbed via specific transport proteins that are highly expressed in the distal ileum. The uptake of bile acids by intestinal epithelial cells modulates the activation of cytosolic and membrane receptors such as the farnesoid X receptor (FXR) and G protein-coupled bile acid receptor 1 (GPBAR1), which has a profound effect on hepatic synthesis of bile acids as well as glucose and lipid metabolism. Extensive research has focused on delineating the processes of bile acid absorption and determining the contribution of dysregulated ileal signaling in the development of intestinal and hepatic disorders. For example, a decrease in the levels of the bile acid-induced ileal hormone FGF15/19 is implicated in bile acid-induced diarrhea (BAD). Conversely, the increase in bile acid absorption with subsequent overload of bile acids could be involved in the pathophysiology of liver and metabolic disorders such as fatty liver diseases and type 2 diabetes mellitus. This review article will attempt to provide a comprehensive overview of the mechanisms involved in the intestinal handling of bile acids, the pathological implications of disrupted intestinal bile acid homeostasis, and the potential therapeutic targets for the treatment of bile acid-related disorders. Published 2020. Compr Physiol 10:21-56, 2020.
胆汁酸的肠回收对于维持其肠肝循环至关重要。大多数胆汁酸通过高度表达于回肠远端的特定转运蛋白被主动吸收。肠上皮细胞摄取胆汁酸可调节细胞质和膜受体的激活,如法尼醇 X 受体(FXR)和 G 蛋白偶联胆汁酸受体 1(GPBAR1),这对肝脏合成胆汁酸以及葡萄糖和脂质代谢有深远的影响。大量研究集中在阐明胆汁酸吸收的过程,并确定回肠信号失调在肠道和肝脏疾病发展中的作用。例如,胆汁酸诱导的回肠激素 FGF15/19 水平降低与胆汁酸诱导的腹泻(BAD)有关。相反,胆汁酸吸收增加,随后胆汁酸过载可能与肝脏和代谢紊乱的病理生理学有关,如脂肪肝和 2 型糖尿病。这篇综述文章将试图全面概述胆汁酸在肠道中的处理机制、肠道胆汁酸稳态失调的病理意义以及胆汁酸相关疾病治疗的潜在治疗靶点。发表于 2020 年。Compr Physiol 10:21-56, 2020.