title: Increased expression of macrophage-inducible C-type lectin in adipose tissue of obese mice and humans.
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.
  
  
  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.
authors.affiliation: Department of Molecular Medicine and Metabolism, Tokyo Medical and Dental University, Tokyo, Japan.
authors.forename: Masayuki
authors.initials: M
authors.lastname: Ichioka
authors.forename: Takayoshi
authors.initials: T
authors.lastname: Suganami
authors.forename: Naoto
authors.initials: N
authors.lastname: Tsuda
authors.forename: Ibuki
authors.initials: I
authors.lastname: Shirakawa
authors.forename: Yoichiro
authors.initials: Y
authors.lastname: Hirata
authors.forename: Noriko
authors.initials: N
authors.lastname: Satoh-Asahara
authors.forename: Yuri
authors.initials: Y
authors.lastname: Shimoda
authors.forename: Miyako
authors.initials: M
authors.lastname: Tanaka
authors.forename: Misa
authors.initials: M
authors.lastname: Kim-Saijo
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Miyamoto
authors.forename: Yasutomi
authors.initials: Y
authors.lastname: Kamei
authors.forename: Masataka
authors.initials: M
authors.lastname: Sata
authors.forename: Yoshihiro
authors.initials: Y
authors.lastname: Ogawa
mesh_terms: D041721:3T3-L1 Cells; D000273:Adipose Tissue / Q000187:drug effects / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D015153:Blotting, Western; D002478:Cells, Cultured; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism; D037181:Lectins, C-Type / Q000235:genetics / Q000378:metabolism*; D016014:Linear Models; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000235:genetics / Q000378:metabolism*; D019308:Palmitic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D051197:Toll-Like Receptor 4 / Q000235:genetics / Q000378:metabolism
chemical_list: C113583:Clecsf8 protein, mouse; D037181:Lectins, C-Type; D008565:Membrane Proteins; D016328:NF-kappa B; D012333:RNA, Messenger; D051197:Toll-Like Receptor 4; D019308:Palmitic Acid