Journal
DIABETES
Volume 60, Issue 3, Pages 819-826Publisher
AMER DIABETES ASSOC
DOI: 10.2337/db10-0864
Keywords
-
Categories
Funding
- Ministry of Education, Culture, Sports, Science, and Technology of Japan
- Ministry of Health, Labour, and Welfare of Japan
- Takeda Science Foundation
- Ono Medical Research Foundation
- Japan Vascular Disease Research Foundation
- Yamaguchi Endocrine Research Foundation
- The Naito Foundation
- Grants-in-Aid for Scientific Research [23659440, 22390159, 23126508, 21117007, 21689026] Funding Source: KAKEN
Ask authors/readers for more resources
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 (Mine le; also called Clec4e and Clecsf9), a type 11 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)-kappa B 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 Mine le 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-kappa B pathway, thereby suggesting its pathophysiologic role in obesity-induced adipose tissue inflammation. Diabetes 60:819-826, 2011
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available