Chronic Over-expression of Fibroblast Growth Factor 21 Increases Bile Acid Biosynthesis by Opposing FGF15/19 Action

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• 作者：Jun Zhang^a ; Jamila Gupte^a ; Yan Gong^a ; Jennifer Weiszmann^a ; Yuan Zhang^c ; Ki Jeong Lee^b ; William G. Richards^b ; Yang Li^a ; ^{yangl@amgen.com}
• 关键词：FGF21 ; FGF19 ; βKlotho ; FGFR4 ; Bile acid metabolism
• 刊名：EBioMedicine
• 出版年：2017
• 出版时间：February 2017
• 年：2017
• 卷：15
• 期：Complete
• 页码：173-183
• 全文大小：1612 K
• 卷排序：15

文摘

Chronic FGF21 overexpression in mice leads to increases in bile acid production and bile acid pool. FGF21 mediates the bile acid changes at least in part through antagonizing FGF15/19 function. Cross-talk between FGF molecules may be a regulatory mechanism for their function. Effects of FGF21 on bile acid metabolism may be relevant to understand FGF21 clinical observations.Pharmacological doses of FGF21 effectively normalize glucose, lipid and energy homeostasis in multiple animal models, and several FGF21 analogs are being evaluated in the clinic as potential therapies for type 2 diabetes. However, a role for FGF21 in the regulation of bile acid metabolism has not been reported. In the present study, we revealed a link between chronic FGF21 overexpression to increases in bile acid synthesis in mice and uncovered a new cross-talk mechanism between FGF molecules. These findings may highlight an importance aspect of FGF21's pharmacology for future clinical study considerations.