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 |
3.469
|
Times Cited |
56
|
WOS Category
|
PHYSIOLOGY
ENDOCRINOLOGY & METABOLISM
|
Resource |
Mice |
RBRC01420 |