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首页> 外文期刊>Hepatology: Official Journal of the American Association for the Study of Liver Diseases >Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice
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Interferon regulatory factor 9 protects against hepatic insulin resistance and steatosis in male mice

机译：干扰素调节因子9可防止雄性小鼠的肝胰岛素抵抗和脂肪变性

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摘要

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.
机译：肥胖是一种卡路里过多的状态，与糖尿病，动脉粥样硬化和某些类型的肿瘤的高风险有关。肥胖可能诱发炎症和胰岛素抵抗（IR）。我们发现，肥胖小鼠肝脏中干扰素（IFN）调节因子9（IRF9）的表达是介导IFN反应的主要转录因子，其水平低于瘦小鼠的肝脏。此外，全身IRF9敲除（KO）小鼠更肥胖，在长期高脂饮食喂养后，IR，肝脂肪变性和炎症加剧。相反，在饮食诱导的和遗传的（ob / ob）肥胖小鼠中，腺病毒介导的肝IRF9过度表达均显示肝胰岛素敏感性显着提高，并且肝脂肪变性和炎症减轻。我们进一步采用了酵母双杂交筛选系统来研究IRF9及其辅因子之间的相互作用。重要的是，我们确定IRF9与过氧化物酶体增殖物激活的受体α（PPAR-α）相互作用，一种重要的代谢相关核受体，可以激活PPAR-α靶基因。此外，肝脏特异性PPAR-α的过量表达挽救了IRF9 KO小鼠的胰岛素敏感性，改善了肝脂肪变性和炎症。结论：IRF9通过与PPAR-α相互作用减轻肝脏IR，脂肪变性和炎症。

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