論文 - 詳細
| RRC ID | 18608 |
|---|---|
| 著者 | 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. |
| タイトル | Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. |
| ジャーナル | Diabetes |
| Abstract |
OBJECTIVE: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. RESEARCH DESIGN AND METHODS: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. RESULTS: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. CONCLUSIONS: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. |
| 巻・号 | 60(3) |
| ページ | 819-26 |
| 公開日 | 2011-3-1 |
| DOI | 10.2337/db10-0864 |
| PII | db10-0864 |
| PMID | 21282371 |
| PMC | PMC3046842 |
| MeSH | 3T3-L1 Cells Adipose Tissue / drug effects Adipose Tissue / metabolism* Analysis of Variance Animals Blotting, Western Cells, Cultured Humans Inflammation / genetics Inflammation / metabolism Lectins, C-Type / genetics Lectins, C-Type / metabolism* Linear Models Macrophages / cytology Macrophages / drug effects Macrophages / metabolism* Male Membrane Proteins / genetics Membrane Proteins / metabolism* Mice NF-kappa B / genetics NF-kappa B / metabolism Obesity / genetics Obesity / metabolism* Palmitic Acid / pharmacology RNA, Messenger / genetics RNA, Messenger / metabolism Reverse Transcriptase Polymerase Chain Reaction Signal Transduction / physiology Toll-Like Receptor 4 / genetics Toll-Like Receptor 4 / metabolism |
| IF | 7.72 |
| 引用数 | 43 |
| WOS 分野 | ENDOCRINOLOGY & METABOLISM |
| リソース情報 | |
| ヒト・動物細胞 | RAW 264(RCB0535) |