Molecular Basis of Bile Acid-FXR-FGF15/19 Signaling Axis

International Journal of Molecular Sciences

Makoto Makishima¹  Takeshi Katafuchi¹ 

[1] Division of Biochemistry, Department of Biomedical Science, Nihon University School of Medicine, Tokyo 173-8610, Japan;

关键词: bile acid;    farnesoid X receptor;    fibroblast growth factor 15/19;   

DOI  :  10.3390/ijms23116046

来源: DOAJ

【 摘 要 】

Bile acids (BAs) are a group of amphiphilic molecules consisting of a rigid steroid core attached to a hydroxyl group with a varying number, position, and orientation, and a hydrophilic side chain. While BAs act as detergents to solubilize lipophilic nutrients in the small intestine during digestion and absorption, they also act as hormones. Farnesoid X receptor (FXR) is a nuclear receptor that forms a heterodimer with retinoid X receptor α (RXRα), is activated by BAs in the enterohepatic circulation reabsorbed via transporters in the ileum and the colon, and plays a critical role in regulating gene expression involved in cholesterol, BA, and lipid metabolism in the liver. The FXR/RXRα heterodimer also exists in the distal ileum and regulates production of fibroblast growth factor (FGF) 15/FGF19, a hormone traveling via the enterohepatic circulation that activates hepatic FGF receptor 4 (FGFR4)-β-klotho receptor complex and regulates gene expression involved in cholesterol, BA, and lipid metabolism, as well as those regulating cell proliferation. Agonists for FXR and analogs for FGF15/19 are currently recognized as a promising therapeutic target for metabolic syndrome and cholestatic diseases.

【 授权许可】

Unknown