Document Detail


Fibroblast growth factor-19 action in the brain reduces food intake and body weight and improves glucose tolerance in male rats.
MedLine Citation:
PMID:  23183168     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Fibroblast growth factor-19 (FGF19) and its rodent ortholog, FGF15, are hormones produced in the distal small intestine and secreted into the circulation after a meal. In addition to controlling the enterohepatic circulation of bile acids, FGF15/19 also regulates systemic lipid and glucose metabolism. In these experiments we investigated the hypothesis that, like other gut-derived postprandial hormones, FGF15/19 can act in the central nervous system to elicit its metabolic effects. We found that FGF-receptors 1 and 4 are present in rat hypothalamus, and that their expression was reduced by up to 60% in high-fat fed rats relative to lean controls. Consistent with a potential role for brain FGF15/19 signaling to regulate energy and glucose homeostasis, and with a previous report that intracerebroventricular (i.c.v.) administration of FGF19 increases energy expenditure, we report that acute i.c.v. FGF19 reduces 24-h food intake and body weight, and acutely improves glucose tolerance. Conversely, i.c.v. administration of an FGF-receptor inhibitor increases food intake and impairs glucose tolerance, suggesting a physiological role for brain FGF receptor signaling. Together, these findings identify the central nervous system as a potentially important target for the beneficial effects of FGF19 in the treatment of obesity and diabetes.
Authors:
Karen K Ryan; Rohit Kohli; Ruth Gutierrez-Aguilar; Shrawan G Gaitonde; Stephen C Woods; Randy J Seeley
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-11-26
Journal Detail:
Title:  Endocrinology     Volume:  154     ISSN:  1945-7170     ISO Abbreviation:  Endocrinology     Publication Date:  2013 Jan 
Date Detail:
Created Date:  2012-12-25     Completed Date:  2013-02-22     Revised Date:  2014-01-09    
Medline Journal Info:
Nlm Unique ID:  0375040     Medline TA:  Endocrinology     Country:  United States    
Other Details:
Languages:  eng     Pagination:  9-15     Citation Subset:  AIM; IM    
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MeSH Terms
Descriptor/Qualifier:
Animals
Body Weight / drug effects*
Brain / drug effects*,  metabolism*
Eating / drug effects*
Energy Metabolism / drug effects
Fibroblast Growth Factors / pharmacology*
Glucose / metabolism*
Humans
Male
Rats
Rats, Long-Evans
Grant Support
ID/Acronym/Agency:
DK017844/DK/NIDDK NIH HHS; DK082173/DK/NIDDK NIH HHS; DK084310/DK/NIDDK NIH HHS; DK093848/DK/NIDDK NIH HHS; HL111319/HL/NHLBI NIH HHS; R01 DK093848/DK/NIDDK NIH HHS
Chemical
Reg. No./Substance:
62031-54-3/Fibroblast Growth Factors; IY9XDZ35W2/Glucose
Comments/Corrections

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