Document Detail


Dual actions of fibroblast growth factor 19 on lipid metabolism.
MedLine Citation:
PMID:  23204296     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Elevated triglyceride (TG) and cholesterol levels are risk factors for cardiovascular disease and are often associated with diabetes and metabolic syndrome. Recent reports suggest that fibroblast growth factor (FGF)19 and FGF21 can dramatically improve metabolic dysfunction, including hyperglycemia, hypertriglyceridemia, and hypercholesterolemia. Due to their similar receptor specificities and co-receptor requirements, FGF19 and FGF21 share many common properties and have been thought to be interchangeable in metabolic regulation. Here we directly compared how pharmacological administration of recombinant FGF19 or FGF21 proteins affect metabolism in B6.V-Lep(ob)/J leptin-deficient mice. FGF19 and FGF21 equally improved glucose parameters; however, we observed increased serum TG and cholesterol levels after treatment with FGF19 but not with FGF21. Increases in serum TGs were also observed after a 4-day treatment with FGF19 in C57BL6/J mice on a high-fat diet. This is in contrast to many literature reports that showed significant improvements in hyperlipidemia after chronic treatment with FGF19 or FGF21 in high-fat diet models. We propose that FGF19 has lipid-raising and lipid-lowering actions mediated through different FGF receptors and target tissues, and the results described here provide a potential mechanism that may explain the inconsistency in the reported effects of FGF19 on lipid metabolism.
Authors:
Xinle Wu; Hongfei Ge; Hélène Baribault; Jamila Gupte; Jennifer Weiszmann; Bryan Lemon; Jonitha Gardner; Preston Fordstrom; Jie Tang; Mingyue Zhou; Minghan Wang; Yang Li
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Publication Detail:
Type:  Journal Article     Date:  2012-12-02
Journal Detail:
Title:  Journal of lipid research     Volume:  54     ISSN:  0022-2275     ISO Abbreviation:  J. Lipid Res.     Publication Date:  2013 Feb 
Date Detail:
Created Date:  2013-01-09     Completed Date:  2013-06-05     Revised Date:  2014-02-04    
Medline Journal Info:
Nlm Unique ID:  0376606     Medline TA:  J Lipid Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  325-32     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Cell Line
Cholesterol / blood
Diet / adverse effects
Fibroblast Growth Factors / chemistry,  pharmacology*
Lipid Metabolism / drug effects*
Liver / drug effects,  metabolism
Male
Mice
Obesity / blood,  etiology
Receptor, Fibroblast Growth Factor, Type 4 / metabolism
Triglycerides / blood
Chemical
Reg. No./Substance:
0/Triglycerides; 62031-54-3/Fibroblast Growth Factors; 97C5T2UQ7J/Cholesterol; EC 2.7.10.1/Fgfr4 protein, mouse; EC 2.7.10.1/Receptor, Fibroblast Growth Factor, Type 4
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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