RRC ID 27776
Author Wang XA, Zhang R, Zhang S, Deng S, Jiang D, Zhong J, Yang L, Wang T, Hong S, Guo S, She ZG, Zhang XD, Li H.
Title Interferon regulatory factor 7 deficiency prevents diet-induced obesity and insulin resistance.
Journal Am. J. Physiol. Endocrinol. Metab.
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.
Volume 305(4)
Pages E485-95
Published 2013-8-15
DOI 10.1152/ajpendo.00505.2012
PII ajpendo.00505.2012
PMID 23695216
MeSH Adiposity Animals Diabetes Mellitus, Type 2 / etiology Diabetes Mellitus, Type 2 / immunology Diabetes Mellitus, Type 2 / metabolism* Diabetes Mellitus, Type 2 / pathology Diet, High-Fat / adverse effects* Endoplasmic Reticulum Stress Energy Metabolism Fatty Liver / etiology Fatty Liver / immunology Fatty Liver / metabolism Fatty Liver / pathology Insulin Resistance* Interferon Regulatory Factor-7 / biosynthesis* Interferon Regulatory Factor-7 / genetics Interferon Regulatory Factor-7 / metabolism Intra-Abdominal Fat / immunology Intra-Abdominal Fat / metabolism* Intra-Abdominal Fat / pathology Liver / immunology Liver / metabolism Liver / pathology Macrophages / immunology Male Mice Mice, Inbred C57BL Mice, Knockout Mice, Obese Muscle, Skeletal / immunology Muscle, Skeletal / metabolism Muscle, Skeletal / pathology Non-alcoholic Fatty Liver Disease Obesity / etiology Obesity / immunology Obesity / metabolism* Obesity / pathology Random Allocation Up-Regulation* Weight Gain
IF 4.125
Times Cited 30
Mice IRF-7 knockout mice C57BL/6J(RBRC01420)