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

54 Citations (Scopus)

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 2011

All Science Journal Classification (ASJC) codes

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Fingerprint Dive into the research topics of 'Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans'. Together they form a unique fingerprint.

  • Cite this

    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, 60(3), 819-826. https://doi.org/10.2337/db10-0864