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学科主题基础医学
Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue
Li, Yang1; Zhang, Heng1; Jiang, Changtao1; Xu, Mingjiang1; Pang, Yanli1; Feng, Juan1; Xiang, Xinxin1; Kong, Wei1; Xu, Guoheng1; Li, Yin1; Wang, Xian1
刊名JOURNAL OF BIOLOGICAL CHEMISTRY
2013-04-05
DOI10.1074/jbc.M112.431627
288期:14页:9583-9592
收录类别SCI
文章类型Article
WOS标题词Science & Technology
类目[WOS]Biochemistry & Molecular Biology
研究领域[WOS]Biochemistry & Molecular Biology
关键词[WOS]UNFOLDED PROTEIN RESPONSE ; ER STRESS ; ACCELERATED ATHEROSCLEROSIS ; MACROPHAGE POLARIZATION ; TRANSCRIPTION FACTOR ; QUALITY CONTROL ; MESSENGER-RNA ; JNK PATHWAY ; OBESITY ; HOMOCYSTEINE
英文摘要

Type 2 diabetes is a chronic inflammatory metabolic disease, the key point being insulin resistance. Endoplasmic reticulum (ER) stress plays a critical role in the pathogenesis of type 2 diabetes. Previously, we found that hyperhomocysteinemia (HHcy) induced insulin resistance in adipose tissue. Here, we hypothesized that HHcy induces ER stress, which in turn promotes insulin resistance. In the present study, the direct effect of Hcy on adipose ER stress was investigated by the use of primary rat adipocytes in vitro and mice with HHcy in vivo. The mechanism and the effect of G protein-coupled receptor 120 (GPR120) were also investigated. We found that phosphorylation or expression of variant ER stress markers was elevated in adipose tissue of HHcy mice. HHcy activated c-Jun N-terminal kinase (JNK), the downstream signal of ER stress in adipose tissue, and activated JNK participated in insulin resistance by inhibiting Akt activation. Furthermore, JNK activated c-Jun and p65, which in turn triggered the transcription of proinflammatory cytokines. Both in vivo and in vitro assays revealed that Hcy-promoted macrophage infiltration aggravated ER stress in adipose tissue. Chemical chaperones PBA and TUDCA could reverse Hcy-induced inflammation and restore insulin-stimulated glucose uptake and Akt activation. Activation of GPR120 reversed Hcy-induced JNK activation and prevented inflammation but not ER stress. Therefore, HHcy inhibited insulin sensitivity in adipose tissue by inducing ER stress, activating JNK to promote proinflammatory cytokine production and facilitating macrophage infiltration. These findings reveal a new mechanism of HHcy in the pathogenesis of insulin resistance.

语种英语
WOS记录号WOS:000317114000002
项目编号81070683 ; 81121061 ; 31230035 ; 81170795 ; 30971085 ; 2011CB503904 ; 2010CB912504 ; NCET-10-0183 ; 7112080
资助机构National Natural Science Foundation of China ; Major National Basic Research Program of China ; Program for New Century Excellent Talents in University ; Beijing Natural Science Foundation
引用统计
被引频次:47[WOS]   [WOS记录]     [WOS相关记录]
文献类型期刊论文
条目标识符http://ir.bjmu.edu.cn/handle/400002259/51593
专题北京大学基础医学院
北京大学第三临床医学院_妇产科
作者单位1.Peking Univ, Sch Basic Med Sci, Dept Physiol & Pathophysiol, Beijing 10091, Peoples R China
2.Minist Educ, Key Lab Mol Cardiovasc Sci, Beijing 100191, Peoples R China
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GB/T 7714
Li, Yang,Zhang, Heng,Jiang, Changtao,et al. Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue[J]. JOURNAL OF BIOLOGICAL CHEMISTRY,2013,288(14):9583-9592.
APA Li, Yang.,Zhang, Heng.,Jiang, Changtao.,Xu, Mingjiang.,Pang, Yanli.,...&Wang, Xian.(2013).Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue.JOURNAL OF BIOLOGICAL CHEMISTRY,288(14),9583-9592.
MLA Li, Yang,et al."Hyperhomocysteinemia Promotes Insulin Resistance by Inducing Endoplasmic Reticulum Stress in Adipose Tissue".JOURNAL OF BIOLOGICAL CHEMISTRY 288.14(2013):9583-9592.
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