Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice.
Hepatology
; 58(2): 603-16, 2013 Aug.
Article
em En
| MEDLINE
| ID: mdl-23471885
ABSTRACT
UNLABELLED Obesity is a calorie-excessive state associated with high risk of diabetes, atherosclerosis, and certain types of tumors. Obesity may induce inflammation and insulin resistance (IR). We found that the expression of interferon (IFN) regulatory factor 9 (IRF9), a major transcription factor mediating IFN responses, was lower in livers of obese mice than in those of their lean counterparts. Furthermore, whole-body IRF9 knockout (KO) mice were more obese and had aggravated IR, hepatic steatosis, and inflammation after chronic high-fat diet feeding. In contrast, adenoviral-mediated hepatic IRF9 overexpression in both diet-induced and genetically (ob/ob) obese mice showed markedly improved hepatic insulin sensitivity and attenuated hepatic steatosis and inflammation. We further employed a yeast two-hybrid screening system to investigate the interactions between IRF9 and its cofactors. Importantly, we identified that IRF9 interacts with peroxisome proliferator-activated receptor alpha (PPAR-α), an important metabolism-associated nuclear receptor, to activate PPAR-α target genes. In addition, liver-specific PPAR-α overexpression rescued insulin sensitivity and ameliorated hepatic steatosis and inflammation in IRF9 KO mice. CONCLUSION:
IRF9 attenuates hepatic IR, steatosis, and inflammation through interaction with PPAR-α.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Fator Gênico 3 Estimulado por Interferon, Subunidade gama
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Fígado Gorduroso
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Fígado
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Obesidade
Tipo de estudo:
Prognostic_studies
Limite:
Animals
Idioma:
En
Revista:
Hepatology
Ano de publicação:
2013
Tipo de documento:
Article
País de afiliação:
China