IR@PKUHSC  > 北京大学基础医学院  > 心血管所
学科主题基础医学
Pro-inflammatory Macrophages suppress PPAR gamma activity in Adipocytes via S-nitrosylation
Yin, Ruiying1,2; Fang, Li1,2; Li, Yingjia1,2; Xue, Peng3; Li, Yazi3; Guan, Youfei4; Chang, Yongsheng5,6; Chen, Chang3; Wang, Nanping1,2,4
关键词PPAR gamma S-nitrosylation Macrophage Adipose tissue Insulin resistance
刊名FREE RADICAL BIOLOGY AND MEDICINE
2015-12-01
DOI10.1016/j.freeradbiomed.2015.10.406
89页:895-905
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology ; Endocrinology & Metabolism
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; National Natural Science Foundation of China ; National Basic Research Program of China
研究领域[WOS]Biochemistry & Molecular Biology ; Endocrinology & Metabolism
关键词[WOS]ACTIVATED-RECEPTOR-GAMMA ; NITRIC-OXIDE SYNTHASE ; ADIPOSE-TISSUE MACROPHAGES ; INSULIN-RESISTANCE ; OXIDATIVE STRESS ; PROTEIN DENITROSYLATION ; TARGETED DISRUPTION ; METABOLIC SYNDROME ; BINDING PROTEIN ; OBESITY
英文摘要

Peroxisome proliferator-activated receptor-gamma (PPAR gamma) is a ligand-activated nuclear receptor and plays an essential role in insulin signaling. Macrophage infiltration into adipose tissue is a character of metabolic inflammation and closely related to insulin resistance in type 2 diabetes. The mechanism by which pro-inflammatory macrophages cause insulin resistance remains to be elucidated. Here we showed that coculture with macrophages significantly suppressed the transcriptional activity of PPAR gamma on its target genes in 3T3-L1 preadipocytes and diabetic primary adipocytes, depending on inducible nitric oxide synthase (iNOS). We further showed that PPAR gamma underwent S-nitrosylation in response to nitrosative stress. Mass-spectrometry and site-directed mutagenesis revealed that S-nitrosylation at cysteine 168 was responsible for the impairment of PPAR gamma function. Extended exposure to NO instigated the proteasome-dependent degradation of PPAR gamma. Consistently, in vivo evidence revealed an association of the decreased PPAR gamma protein level with increased macrophage infiltration in visceral adipose tissue (VAT) of obese diabetic db/db mice. Together, our results demonstrated that pro-inflammatory macrophages suppressed PPAR gamma activity in adipocytes via S-nitrosylation, suggesting a novel mechanism linking metabolic inflammation with insulin resistance. (C) 2015 Elsevier Inc. All rights reserved.

语种英语
所属项目编号31430045 ; 81470373 ; 81220108005 ; 31225012 ; 2011CB910900 ; 2012CB911000
资助者National Natural Science Foundation of China ; National Basic Research Program of China ; National Natural Science Foundation of China ; National Basic Research Program of China
WOS记录号WOS:000366355800084
Citation statistics
Cited Times:10[WOS]   [WOS Record]     [Related Records in WOS]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/67578
Collection北京大学基础医学院_心血管所
作者单位1.Peking Union Med Coll, Beijing 100005, Peoples R China
2.Peking Univ, Ctr Diabet, Beijing 100191, Peoples R China
3.Peking Univ, Inst Cardiovasc Sci, Beijing 100191, Peoples R China
4.Chinese Acad Sci, Inst Biophys, Beijing 100101, Peoples R China
5.Dalian Med Univ, Adv Inst Med Sci, Dalian 116044, Peoples R China
6.Chinese Acad Med Sci, Inst Basic Med Sci, Natl Lab Med Mol Biol, Beijing 100005, Peoples R China
Recommended Citation
GB/T 7714
Yin, Ruiying,Fang, Li,Li, Yingjia,et al. Pro-inflammatory Macrophages suppress PPAR gamma activity in Adipocytes via S-nitrosylation[J]. FREE RADICAL BIOLOGY AND MEDICINE,2015,89:895-905.
APA Yin, Ruiying.,Fang, Li.,Li, Yingjia.,Xue, Peng.,Li, Yazi.,...&Wang, Nanping.(2015).Pro-inflammatory Macrophages suppress PPAR gamma activity in Adipocytes via S-nitrosylation.FREE RADICAL BIOLOGY AND MEDICINE,89,895-905.
MLA Yin, Ruiying,et al."Pro-inflammatory Macrophages suppress PPAR gamma activity in Adipocytes via S-nitrosylation".FREE RADICAL BIOLOGY AND MEDICINE 89(2015):895-905.
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