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

Research output: Contribution to journalArticle

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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.

Original languageEnglish
Pages (from-to)819-826
Number of pages8
JournalDiabetes
Volume60
Issue number3
DOIs
Publication statusPublished - Mar 1 2011
Externally publishedYes

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C-Type Lectins
Obese Mice
Adipose Tissue
Macrophages
Adipocytes
Obesity
Messenger RNA
Fatty Acids
Inbred C3H Mouse
Bone Marrow Cells
Inflammation
Toll-Like Receptor 4
Palmitates
Lipolysis
Microarray Analysis
Coculture Techniques
Oligonucleotide Array Sequence Analysis

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

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

Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. / Ichioka, Masayuki; Suganami, Takayoshi; Tsuda, Naoto; Shirakawa, Ibuki; Hirata, Yoichiro; Satoh-Asahara, Noriko; Shimoda, Yuri; Tanaka, Miyako; Kim-Saijo, Misa; Miyamoto, Yoshihiro; Kamei, Yasutomi; Sata, Masataka; Ogawa, Yoshihiro.

In: Diabetes, Vol. 60, No. 3, 01.03.2011, p. 819-826.

Research output: Contribution to journalArticle

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 2011, 'Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans', Diabetes, vol. 60, no. 3, pp. 819-826. https://doi.org/10.2337/db10-0864
Ichioka M, Suganami T, Tsuda N, Shirakawa I, Hirata Y, Satoh-Asahara N et al. Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. Diabetes. 2011 Mar 1;60(3):819-826. https://doi.org/10.2337/db10-0864
Ichioka, Masayuki ; Suganami, Takayoshi ; Tsuda, Naoto ; Shirakawa, Ibuki ; Hirata, Yoichiro ; Satoh-Asahara, Noriko ; Shimoda, Yuri ; Tanaka, Miyako ; Kim-Saijo, Misa ; Miyamoto, Yoshihiro ; Kamei, Yasutomi ; Sata, Masataka ; Ogawa, Yoshihiro. / Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans. In: Diabetes. 2011 ; Vol. 60, No. 3. pp. 819-826.
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AU - Hirata, Yoichiro

AU - Satoh-Asahara, Noriko

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AU - Kamei, Yasutomi

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