Asgharpour Amon, Kumar Divya, Sanyal Arun
Virginia Commonwealth University, MCV Box 980341, Richmond, VA, 23298-0341, USA.
Hepatol Int. 2015 Oct;9(4):527-33. doi: 10.1007/s12072-015-9656-7. Epub 2015 Aug 29.
Bile acids are well known for their effects on cholesterol homeostasis and lipid digestion. Since the discovery of bile acid receptors, of which there are farnesoid X receptor (FXR), a nuclear receptor, and the plasma membrane G-protein receptor, as well as Takeda G-protein coupled receptor clone 5, further roles have been elucidated for bile acids including glucose and lipid metabolism as well as inflammation. Additionally, treatment with bile acid receptor agonists has shown a decrease in the amount of atherosclerosis plaque formation and decreased portal vascular resistance and portal hypotension in animal models. Furthermore, rodent models have demonstrated antifibrotic activity using bile acid receptor agonists. Early human data using a FXR agonist, obeticholic acid, have shown promising results with improvement of histological activity and even a reduction of fibrosis. Human studies are ongoing and will provide further information on bile acid receptor agonist therapies. Thus, bile acids and their derivatives have the potential for management of liver diseases and potentially other disease states including diabetes and the metabolic syndrome.
胆汁酸因其对胆固醇稳态和脂质消化的作用而广为人知。自从发现胆汁酸受体以来，其中包括法尼醇X受体（FXR，一种核受体）、质膜G蛋白受体以及武田G蛋白偶联受体克隆5，胆汁酸的其他作用也已得到阐明，包括葡萄糖和脂质代谢以及炎症。此外，在动物模型中，用胆汁酸受体激动剂治疗已显示动脉粥样硬化斑块形成量减少，门静脉血管阻力降低以及门静脉高压减轻。此外，啮齿动物模型已证明使用胆汁酸受体激动剂具有抗纤维化活性。使用FXR激动剂奥贝胆酸的早期人体数据已显示出令人鼓舞的结果，组织学活性得到改善，甚至纤维化减轻。人体研究正在进行中，将提供有关胆汁酸受体激动剂疗法的更多信息。因此，胆汁酸及其衍生物具有治疗肝脏疾病以及可能包括糖尿病和代谢综合征在内的其他疾病状态的潜力。
