title: A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling.
abstract: OBJECTIVE
  Obesity and hyperlipidaemia are associated with insulin resistance (IR); however, the mechanisms responsible remain incompletely understood. Pro-atherogenic hyperlipidaemic states are characterized by inflammation, oxidant stress, and pathophysiologic oxidized lipids, including ligands for the scavenger receptor CD36. Here we tested the hypothesis that the absence of CD36 protects mice from IR associated with diet-induced obesity and hyperlipidaemia.
  
  
  RESULTS
  Adipose tissue from CD36(-/-) mice demonstrated a less inflammatory phenotype and improved insulin signalling in vivo and at the level of the adipocyte and macrophage. The pathophysiologic ligand oxidized low-density lipoprotein (oxLDL) activated c-Jun N-terminal kinase (JNK) and disrupted insulin signalling in both adipocytes and macrophages in a CD36-dependent manner. Macrophages isolated from CD36(-/-) mice after high-fat diet feeding elicited less JNK activation and inhibition of insulin signalling in adipocytes after co-culture compared with wild-type macrophages.
  
  
  CONCLUSIONS
  These data suggest that a CD36-dependent inflammatory paracrine loop between adipocytes and macrophages facilitates chronic inflammation and contributes to IR common in obesity and dyslipidaemia.
authors.affiliation: Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH 44195, USA.
authors.forename: David J
authors.initials: DJ
authors.lastname: Kennedy
authors.forename: Sai
authors.initials: S
authors.lastname: Kuchibhotla
authors.forename: Kristen M
authors.initials: KM
authors.lastname: Westfall
authors.forename: Roy L
authors.initials: RL
authors.lastname: Silverstein
authors.forename: Richard E
authors.initials: RE
authors.lastname: Morton
authors.forename: Maria
authors.initials: M
authors.lastname: Febbraio
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology* / Q000378:metabolism; D000818:Animals; D018955:CD36 Antigens / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D002478:Cells, Cultured; D018920:Coculture Techniques; D050171:Dyslipidemias / Q000276:immunology / Q000378:metabolism; D005260:Female; D018149:Glucose Intolerance / Q000276:immunology / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism*; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance / Q000276:immunology; D008077:Lipoproteins, LDL / Q000378:metabolism; D008264:Macrophages / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009765:Obesity / Q000276:immunology / Q000378:metabolism; D015398:Signal Transduction / Q000276:immunology*
chemical_list: D018955:CD36 Antigens; D007328:Insulin; D008077:Lipoproteins, LDL; C099252:oxidized low density lipoprotein