Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans.
Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans.
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作者：
Ichioka M;Suganami T;Tsuda N;Shirakawa I;Hirata Y;Satoh-Asahara N;Shimoda Y;Tanaka M;Kim-Saijo M;Miyamoto Y;Kamei Y;Sata M;Ogawa Y
我们提供的证据表明，饱和脂肪酸，这是从脂肪细胞释放通过巨噬细胞诱导的脂肪细胞脂解，作为一个天然存在的配体的Toll样受体（TLR）4复合物在巨噬细胞，从而加重肥胖诱导的脂肪组织炎症。本研究的目的是鉴定肥胖症脂肪组织巨噬细胞中激活的分子。我们对3 T3-L1脂肪细胞和RAW 264巨噬细胞的共培养进行了cDNA微阵列分析。培养的脂肪细胞和巨噬细胞以及肥胖小鼠和人的脂肪组织用于检查mRNA和蛋白质表达。我们发现巨噬细胞诱导的C型凝集素（Mincle;也称为Clec 4 e和Clecsf 9），一种II型跨膜C型凝集素，在脂肪细胞和巨噬细胞之间的相互作用期间在巨噬细胞中被选择性地诱导。棕榈酸酯（3 T3-L1脂肪细胞释放的主要饱和脂肪酸）处理至少部分通过TLR 4/核因子（NF）-κB途径诱导巨噬细胞中Mincle mRNA表达。在肥胖小鼠和人的脂肪组织中，Mincle mRNA表达与巨噬细胞标志物平行增加。相对于对照C3 H/HeN小鼠，TLR 4信号传导缺陷的C3 H/HeJ小鼠中肥胖诱导的Mincle mRNA表达增加显着减弱。值得注意的是，Mincle mRNA在骨髓细胞（BMC）衍生的促炎M1巨噬细胞中表达，而不是在体外BMC衍生的抗炎M2巨噬细胞中表达。我们的数据表明，Mincle在肥胖症的脂肪组织巨噬细胞中至少部分地通过饱和脂肪酸/TLR 4/NF-κB途径被诱导，从而表明其在肥胖症诱导的脂肪组织炎症中的病理生理作用。
We have provided evidence that saturated fatty acids, which are released from adipocytes via macrophage-induced adipocyte lipolysis, serve as a naturally occurring ligand for the Toll-like receptor (TLR) 4 complex in macrophages, thereby aggravating obesity-induced adipose tissue inflammation. The aim of this study was to identify the molecule(s) activated in adipose tissue macrophages in obesity. We performed a cDNA microarray analysis of coculture of 3T3-L1 adipocytes and RAW264 macrophages. Cultured adipocytes and macrophages and the adipose tissue of obese mice and humans were used to examine mRNA and protein expression. We found that macrophage-inducible C-type lectin (Mincle; also called Clec4e and Clecsf9), a type II transmembrane C-type lectin, is induced selectively in macrophages during the interaction between adipocytes and macrophages. Treatment with palmitate, a major saturated fatty acid released from 3T3-L1 adipocytes, induced Mincle mRNA expression in macrophages at least partly through the TLR4/nuclear factor (NF)-κB pathway. Mincle mRNA expression was increased in parallel with macrophage markers in the adipose tissue of obese mice and humans. The obesity-induced increase in Mincle mRNA expression was markedly attenuated in C3H/HeJ mice with defective TLR4 signaling relative to control C3H/HeN mice. Notably, Mincle mRNA was expressed in bone-marrow cell (BMC)-derived proinflammatory M1 macrophages rather than in BMC-derived anti-inflammatory M2 macrophages in vitro. Our data suggest that Mincle is induced in adipose tissue macrophages in obesity at least partly through the saturated fatty acid/TLR4/NF-κB pathway, thereby suggesting its pathophysiologic role in obesity-induced adipose tissue inflammation.
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影响因子：
4.8
作者：
Hironaka, N;Mochida, K;Yamaoka, S
通讯作者：
Yamaoka, S
影响因子：
4.4
作者：
Martinez, Fernando O.;Gordon, Siamon;Mantovani, Alberto
通讯作者：
Mantovani, Alberto
DOI：
10.1161/atvbaha.106.136853
发表时间：
2007-09-01
影响因子：
8.7
作者：
Itoh, Michiko;Suganami, Takayoshi;Ogawa, Yoshihiro
通讯作者：
Ogawa, Yoshihiro
DOI：
10.4049/jimmunol.0904013
发表时间：
2010-03-15
期刊：
Journal of immunology (Baltimore, Md. : 1950)
影响因子：
--
作者：
Schoenen H;Bodendorfer B;Hitchens K;Manzanero S;Werninghaus K;Nimmerjahn F;Agger EM;Stenger S;Andersen P;Ruland J;Brown GD;Wells C;Lang R
通讯作者：
Lang R
影响因子：
4.8
作者：
Lee, JY;Sohn, KH;Hwang, D
通讯作者：
Hwang, D