The Radioprotective 105/MD-1 Complex Contributes to Diet-Induced Obesity and Adipose Tissue Inflammation

被引：40

作者：

Watanabe, Yasuharu ^{[1
]}

Nakamura, Tomoya ^{[1
]}

Ishikawa, Sho ^{[1
]}

Fujisaka, Shiho ^{[2
]}

Usui, Isao ^{[2
]}

Tsuneyama, Koichi ^{[3
]}

Ichihara, Yoshinori ^{[4
]}

Wada, Tsutomu ^{[4
]}

Hirata, Yoichiro ^{[5
]}

Suganami, Takayoshi ^{[6
]}

Izaki, Hirofumi ^{[7
]}

Akira, Shizuo ^{[8
]}

Miyake, Kensuke ^{[9
]}

Kanayama, Hiro-omi ^{[7
]}

Shimabukuro, Michio ^{[10
]}

Sata, Masataka ^{[5
]}

Sasaoka, Toshiyasu ^{[4
]}

Ogawa, Yoshihiro ^{[6
]}

Tobe, Kazuyuki ^{[2
]}

Takatsu, Kiyoshi ^{[1
,11
]}

Nagai, Yoshinori ^{[1
]}

机构：

[1] Toyama Univ, Dept Immunobiol & Pharmacol Genet, Grad Sch Med & Pharmaceut Sci Res, Toyama 930, Japan

[2] Toyama Univ, Dept Internal Med 1, Grad Sch Med & Pharmaceut Sci Res, Toyama 930, Japan

[3] Toyama Univ, Dept Diagnost Pathol, Grad Sch Med & Pharmaceut Sci Res, Toyama 930, Japan

[4] Toyama Univ, Dept Clin Pharmacol, Grad Sch Med & Pharmaceut Sci Res, Toyama 930, Japan

[5] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Cardiovasc Med, Tokushima 770, Japan

[6] Tokyo Med & Dent Univ, Med Res Inst, Dept Mol Med & Metab, Tokyo, Japan

[7] Univ Tokushima, Dept Urol, Inst Hlth Biosci, Grad Sch, Tokushima 770, Japan

[8] Osaka Univ, Host Def Lab, WPI Immunol Frontier Res Ctr, Osaka, Japan

[9] Univ Tokyo, Inst Med Sci, Dept Microbiol & Immunol, Div Infect Genet, Tokyo, Japan

[10] Univ Tokushima, Grad Sch, Inst Hlth Biosci, Dept Cardiodiabet Med, Tokushima 770, Japan

[11] Toyama Prefectural Inst Pharmaceut Res, Toyama, Japan

来源：

DIABETES | 2012年 / 61卷 / 05期

关键词：

INDUCED INSULIN-RESISTANCE; FREE FATTY-ACIDS; INNATE IMMUNITY; CRYSTAL-STRUCTURE; MOUSE MD-1; B-CELLS; RP105; LIPOPOLYSACCHARIDE; RESPONSIVENESS; MACROPHAGES;

D O I：

10.2337/db11-1182

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Recent accumulating evidence suggests that innate immunity is associated with obesity-induced chronic inflammation and metabolic disorders. Here, we show that a Toll-like receptor (TLR) protein, radioprotective 105 (RP105)/myeloid differentiation protein (MD)-1 complex, contributes to high-fat diet (HFD)-induced obesity, adipose tissue inflammation, and insulin resistance. An HFD dramatically increased RP105 mRNA and protein expression in stromal vascular fraction of epididymal white adipose tissue (eWAT) in wild-type (WT) mice. RP105 mRNA expression also was significantly increased in the visceral adipose tissue of obese human subjects relative to nonobese subjects. The RP105/MD-1 complex was expressed by most adipose tissue macrophages (ATMs). An HFD increased RP105/MD-1 expression on the M1 subset of ATMs that accumulate in eWAT. Macrophages also acquired this characteristic in coculture with 3T3-L1 adipocytes. RP105 knockout (KO) and MD-1 KO mice had less HFD-induced adipose tissue inflammation, hepatic steatosis, and insulin resistance compared with wild-type (WT) and TLR4 KO mice. Finally, the saturated fatty acids, palmitic and stearic acids, are endogenous ligancls for TLR4, but they did not activate RP105/MD-1. Thus, the RP105/MD-1 complex is a major mediator of adipose tissue inflammation independent of TLR4 signaling and may represent a novel therapeutic target for obesity-associated metabolic disorders. Diabetes 61:1199-1209, 2012

引用

页码：1199 / 1209

页数：11

共 39 条

[1] Interaction between free fatty acids and glucose metabolism [J].