期刊
DIGESTIVE DISEASES
卷 33, 期 3, 页码 327-331出版社
KARGER
DOI: 10.1159/000371670
关键词
Nuclear receptor; Fibroblast growth factor; Ileum; Liver; CYP7A1
资金
- National Institutes of Health [DK067158]
- Robert A. Welch Foundation [I-1588, I-1275]
- Howard Hughes Medical Institute
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [R01DK067158] Funding Source: NIH RePORTER
While it has long been recognized that bile acids are essential for solubilizing lipophilic nutrients in the small intestine, the discovery in 1999 that bile acids serve as ligands for the nuclear receptor farnesoid X receptor (FXR) opened the floodgates in terms of characterizing their actions as selective signaling molecules. Bile acids act on FXR in ileal enterocytes to induce the expression of fibroblast growth factor (FGF)15/19, an atypical FGF that functions as a hormone. FGF15/19 subsequently acts on a cell surface receptor complex in hepatocytes to repress bile acid synthesis and gluconeogenesis, and to stimulate glycogen and protein synthesis. FGF15/19 also stimulates gallbladder filling. Thus, the bile acid-FXR-FGF15/19 signaling pathway regulates diverse aspects of the postprandial enterohepatic response. Pharmacologically, this endocrine pathway provides exciting new opportunities for treating metabolic disease and bile acid-related disorders such as primary biliary cirrhosis and bile acid diarrhea. Both FXR agonists and FGF19 analogs are currently in clinical trials. (C) 2015 S. Karger AG, Basel
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