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2015 ; 33
(3
): 327-31
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Bile Acids as Hormones: The FXR-FGF15/19 Pathway
#MMPMID26045265
Kliewer SA
; Mangelsdorf DJ
Dig Dis
2015[]; 33
(3
): 327-31
PMID26045265
show ga
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.
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