A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling. Cardiovasc Res 2011 Feb 15;89(3):604-13
Date
11/23/2010Pubmed ID
21088116Pubmed Central ID
PMC3028977DOI
10.1093/cvr/cvq360Scopus ID
2-s2.0-79551501139 (requires institutional sign-in at Scopus site) 147 CitationsAbstract
AIMS: 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.
METHODS AND 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.
CONCLUSION: 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.
Author List
Kennedy DJ, Kuchibhotla S, Westfall KM, Silverstein RL, Morton RE, Febbraio MAuthor
Roy L. Silverstein MD Professor in the Medicine department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
AdipocytesAdipose Tissue
Animals
CD36 Antigens
Cells, Cultured
Coculture Techniques
Dyslipidemias
Female
Glucose Intolerance
Inflammation
Insulin
Insulin Resistance
Lipoproteins, LDL
Macrophages
Male
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Obesity
Signal Transduction
