Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans

Masayuki Ichioka, Takayoshi Suganami, Naoto Tsuda, Ibuki Shirakawa, Yoichiro Hirata, Noriko Satoh-Asahara, Yuri Shimoda, Miyako Tanaka, Misa Kim-Saijo, Yoshihiro Miyamoto, Yasutomi Kamei, Masataka Sata, Yoshihiro Ogawa

研究成果: ジャーナルへの寄稿記事

52 引用 (Scopus)

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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.

元の言語英語
ページ(範囲)819-826
ページ数8
ジャーナルDiabetes
60
発行部数3
DOI
出版物ステータス出版済み - 3 1 2011
外部発表Yes

    フィンガープリント

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

これを引用

Ichioka, M., Suganami, T., Tsuda, N., Shirakawa, I., Hirata, Y., Satoh-Asahara, N., ... Ogawa, Y. (2011). Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. Diabetes, 60(3), 819-826. https://doi.org/10.2337/db10-0864