title: Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance.
abstract: 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.
authors.affiliation: Department of Cardiology, Renmin Hospital of Wuhan University, Wuhan, China;
authors.forename: Xin-An
authors.initials: XA
authors.lastname: Wang
authors.forename: Ran
authors.initials: R
authors.lastname: Zhang
authors.forename: Shumin
authors.initials: S
authors.lastname: Zhang
authors.forename: Shan
authors.initials: S
authors.lastname: Deng
authors.forename: Dingsheng
authors.initials: D
authors.lastname: Jiang
authors.forename: Jinfeng
authors.initials: J
authors.lastname: Zhong
authors.forename: Li
authors.initials: L
authors.lastname: Yang
authors.forename: Tao
authors.initials: T
authors.lastname: Wang
authors.forename: Shufen
authors.initials: S
authors.lastname: Hong
authors.forename: Sen
authors.initials: S
authors.lastname: Guo
authors.forename: Zhi-Gang
authors.initials: ZG
authors.lastname: She
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Zhang
authors.forename: Hongliang
authors.initials: H
authors.lastname: Li
mesh_terms: D050154:Adiposity; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D059305:Diet, High-Fat / Q000009:adverse effects*; D059865:Endoplasmic Reticulum Stress; D004734:Energy Metabolism; D005234:Fatty Liver / Q000209:etiology / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050839:Interferon Regulatory Factor-7 / Q000096:biosynthesis* / Q000235:genetics / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008264:Macrophages / Q000276:immunology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D008820:Mice, Obese; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D065626:Non-alcoholic Fatty Liver Disease; D009765:Obesity / Q000209:etiology / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D011897:Random Allocation; D015854:Up-Regulation; D015430:Weight Gain
chemical_list: D050839:Interferon Regulatory Factor-7; C494235:Irf7 protein, mouse
keywords: adiposity; fatty liver; inflammation; type 2 diabetes