Fibroblast growth factor receptor 4 (FGFR4) deficiency improves insulin resistance and glucose metabolism under diet-induced obesity conditions.
J Biol Chem
; 289(44): 30470-30480, 2014 Oct 31.
Article
em En
| MEDLINE
| ID: mdl-25204652
ABSTRACT
The role of fibroblast growth factor receptor 4 (FGFR4) in regulating bile acid synthesis has been well defined; however, its reported role on glucose and energy metabolism remains unresolved. Here, we show that FGFR4 deficiency in mice leads to improvement in glucose metabolism, insulin sensitivity, and reduction in body weight under high fat conditions. Mechanism of action studies in FGFR4-deficient mice suggest that the effects are mediated in part by increased plasma levels of adiponectin and the endocrine FGF factors FGF21 and FGF15, the latter of which increase in response to an elevated bile acid pool. Direct actions of increased bile acids on bile acid receptors, and other potential indirect mechanisms, may also contribute to the observed metabolic changes. The results described herein suggest that FGFR4 antagonists alone, or in combination with other agents, could serve as a novel treatment for diabetes.
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Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Receptor Tipo 4 de Fator de Crescimento de Fibroblastos
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Dieta Hiperlipídica
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Obesidade
Tipo de estudo:
Etiology_studies
Limite:
Animals
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Female
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Humans
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Male
Idioma:
En
Ano de publicação:
2014
Tipo de documento:
Article