Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China;
Am J Physiol Endocrinol Metab. 2013 Aug 15;305(4):E485-95. doi: 10.1152/ajpendo.00505.2012. Epub 2013 May 21.
Obesity-related inflammation has been implicated in the pathogenesis of insulin resistance and type 2 diabetes. In this study, we addressed the potential role of interferon regulatory factor 7 (IRF7), a master regulator of type I interferon-dependent immune responses, in the regulation of energy metabolism. The expression levels of IRF7 were increased in white adipose tissue, liver tissue, and gastrocnemius muscle of both diet-induced obese mice and ob/ob mice compared with their lean counterparts. After feeding a high-fat diet (HFD) for 24 wk, IRF7 knockout (KO) mice showed less weight gain and adiposity than wild-type controls. KO of IRF7 improved glucose and lipid homeostasis and insulin sensitivity. Additionally, KO of IRF7 ameliorated diet-induced hepatic steatosis. Next, we assessed the inflammatory state of the IRF7 KO mice on the HFD. These mice showed less macrophage infiltration into multiple organs and were protected from local and systemic inflammation. This study demonstrates a role for IRF7 in diet-induced alterations in energy metabolism and insulin sensitivity. Our results also suggest that IRF7 is involved in the etiology of metabolic abnormalities, which suggests a new strategy for treating obesity and type 2 diabetes.
肥胖相关炎症与胰岛素抵抗和 2 型糖尿病的发病机制有关。在这项研究中，我们研究了干扰素调节因子 7（IRF7）在调节能量代谢中的潜在作用，IRF7 是 I 型干扰素依赖的免疫反应的主要调节因子。与瘦鼠相比，饮食诱导肥胖的小鼠和 ob/ob 小鼠的白色脂肪组织、肝组织和比目鱼肌中的 IRF7 表达水平增加。用高脂肪饮食（HFD）喂养 24 周后，IRF7 敲除（KO）小鼠比野生型对照体重增加和肥胖程度降低。IRF7 的 KO 改善了葡萄糖和脂质稳态以及胰岛素敏感性。此外，IRF7 的 KO 改善了饮食诱导的肝脂肪变性。接下来，我们评估了 HFD 上 IRF7 KO 小鼠的炎症状态。这些小鼠的多个器官中巨噬细胞浸润较少，并且免受局部和全身炎症的影响。这项研究表明 IRF7 在饮食诱导的能量代谢和胰岛素敏感性改变中起作用。我们的结果还表明，IRF7 参与代谢异常的病因，这表明治疗肥胖和 2 型糖尿病的一种新策略。
