Division of Gastroenterology, Hepatology and Nutrition, Children's Hospital Los Angeles, Keck School of Medicine, University of Southern California, Los Angeles, CA, United States.
Front Endocrinol (Lausanne). 2022 Jan 18;12:799648. doi: 10.3389/fendo.2021.799648. eCollection 2021.
Bile acids are the catabolic end products of cholesterol metabolism that are best known for their role in the digestion of lipids. In the last two decades, extensive investigation has shown bile acids to be important signaling molecules in metabolic processes throughout the body. Bile acids are ligands that can bind to several receptors, including the nuclear receptor farnesoid X receptor (FXR) in ileal enterocytes. FXR activation induces the expression of fibroblast growth factor (FGF) 15/19, a hormone that can modulate bile acid levels, repress gluconeogenesis and lipogenesis, and promote glycogen synthesis. Recent studies have described a novel intestinal protein, MAM and LDL Receptor Class A Domain containing 1 (MALRD1) that positively affects FGF15/19 levels. This signaling pathway presents an exciting target for treating metabolic disease and bile acid-related disorders.
胆汁酸是胆固醇代谢的分解产物，以其在脂质消化中的作用而闻名。在过去的二十年中，广泛的研究表明胆汁酸是全身代谢过程中的重要信号分子。胆汁酸是配体，可以与几种受体结合，包括回肠肠细胞中的核受体法尼醇 X 受体 (FXR)。FXR 激活诱导成纤维细胞生长因子 (FGF) 15/19 的表达，这是一种可以调节胆汁酸水平、抑制糖异生和脂肪生成、促进糖原合成的激素。最近的研究描述了一种新型肠道蛋白，MAM 和 LDL 受体 A 结构域包含 1（MALRD1），它可以正向影响 FGF15/19 的水平。这条信号通路为治疗代谢疾病和胆汁酸相关疾病提供了一个令人兴奋的靶点。
