Inflammation and endoplasmic reticulum stress in obesity and diabetes

被引：203

作者：

Hotamisligil, G. S. ^{[1
]}

机构：

[1] Harvard Univ, Sch Publ Hlth, Dept Nutr, Dept Genet & Complex Dis, Boston, MA 02115 USA

来源：

INTERNATIONAL JOURNAL OF OBESITY | 2008年 / 32卷 / Suppl 7期

关键词：

insulin resistance; protein folding; immune response; unfolded protein response (UPR); c-Jun N-terminal kinase (JNK); adipose tissue;

D O I：

10.1038/ijo.2008.238

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Obesity is associated with chronic low-grade inflammation. Inflammatory signals interfere with insulin action and disrupt metabolic homeostasis. The c-Jun N-terminal kinase (JNK) has been identified as a central mediator of insulin resistance. Recent studies showed that in obesity compromising endoplasmic reticulum (ER) function results in insulin resistance and type 2 diabetes that are dependent on JNK activation. In contrast, enhancing ER function in transgenic mice or by the use of chemical chaperones protects against diet-induced insulin resistance. Hence, ER stress and the related signaling networks present a critical mechanism underlying obesity-induced JNK activity, inflammatory response and insulin resistance.

引用

页码：S52 / S54

页数：3

共 12 条

[1] Adipocyte/macrophage fatty acid-binding proteins contribute to metabolic deterioration through actions in both macrophages and adipocytes in mice [J].

Furuhashi, Masato ;

Fucho, Raquel ;

Gorgun, Cem Z. ;

Tuncman, Guerol ;

Cao, Haiming ;

Hotamisligil, Goekhan S. .

JOURNAL OF CLINICAL INVESTIGATION, 2008, 118 (07) :2640-2650

[2] Treatment of diabetes and atherosclerosis by inhibiting fatty-acid-binding protein aP2 [J].

Furuhashi, Masato ;

Tuncman, Guerol ;

Goerguen, Cem Z. ;

Makowski, Liza ;

Atsumi, Genichi ;

Vaillancourt, Eric ;

Kono, Keita ;

Babaev, Vladimir R. ;

Fazio, Sergio ;

Linton, MacRae F. ;

Sulsky, Richard ;

Robl, Jeffrey A. ;

Parker, Rex A. ;

Hotamisligil, Goekhan S. .

NATURE, 2007, 447 (7147) :959-U2

[3] Adipocyte stress: the endoplasmic reticulum and metabolic disease [J].

Gregor, Margaret F. ;

Hotamisligil, Goekhan S. .

JOURNAL OF LIPID RESEARCH, 2007, 48 (09) :1905-1914

[4] A central role for JNK in obesity and insulin resistance [J].

Hirosumi, J ;

Tuncman, G ;

Chang, LF ;

Görgün, CZ ;

Uysal, KT ;

Maeda, K ;

Karin, M ;

Hotamisligil, GS .

NATURE, 2002, 420 (6913) :333-336

[5] Inflammation and metabolic disorders [J].

Hotamisligil, Goekhan S. .

NATURE, 2006, 444 (7121) :860-867

[6] Role of endoplasmic reticulum stress and c-Jun NH2-terminal kinase pathways in inflammation and origin of obesity and diabetes [J].

Hotamisligil, GS .

DIABETES, 2005, 54 :S73-S78

[7] Chemical chaperones reduce ER stress and restore glucose homeostasis in a mouse model of type 2 diabetes [J].

Oezcan, Umut ;

Yilmaz, Erkan ;

Oezcan, Lale ;

Furuhashi, Masato ;

Vaillancourt, Eric ;

Smith, Ross O. ;

Goerguen, Cem Z. ;

Hotamisligil, Goekhan S. .

SCIENCE, 2006, 313 (5790) :1137-1140

[8] Endoplasmic reticulum stress links obesity, insulin action, and type 2 diabetes [J].

Özcan, U ;

Cao, Q ;

Yilmaz, E ;

Lee, AH ;

Iwakoshi, NN ;

Özdelen, E ;

Tuncman, G ;

Görgün, C ;

Glimcher, LH ;

Hotamisligil, GS .

SCIENCE, 2004, 306 (5695) :457-461

[9] Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance [J].

Tuncman, Gurol ;

Hirosumi, Jiro ;

Solinas, Giovanni ;

Chang, Lufen ;

Karin, Michael ;

Hotamisligil, Gokhan S. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2006, 103 (28) :10741-10746

[10] A Predominant Role for Parenchymal c-Jun Amino Terminal Kinase (JNK) in the Regulation of Systemic Insulin Sensitivity [J].

Vallerie, Sara N. ;

Furuhashi, Masato ;

Fucho, Raquel ;

Hotamisligil, Goekhan S. .

PLOS ONE, 2008, 3 (09)

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