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CD36 Mediates a Pro‐inflammatory Signaling Loop in Fat and Contributes to Insulin Resistance
Author(s) -
Kennedy David J,
Silverstein Roy L,
Febbraio Maria
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.856.8
Subject(s) - cd36 , adipocyte , adipose tissue , insulin resistance , chemistry , endocrinology , medicine , scavenger receptor , proinflammatory cytokine , phosphorylation , inflammation , insulin , biology , receptor , biochemistry , cholesterol , lipoprotein
Scavenger receptor CD36 recognizes ligands generated in pro‐atherogenic hyperlipidemic (PA‐HL) states, including oxidized LDL (oxLDL). Systemic levels of oxLDL are highly associated with insulin resistance (IR). We hypothesized that CD36 ligands generated in PA‐HL states disrupt insulin signaling in adipocytes via CD36‐dependent signaling. CD36 + and CD36 − mice were fed a high‐fat diet for 8 weeks and examined for markers of IR. Compared to CD36 + , CD36 − mice had improved glucose tolerance and both decreased JNK and inhibitory IRS‐1 serine phosphorylation in adipose tissue. Further, macrophages from CD36 − mice demonstrated decreased production of ROS and proinflammatory cytokines, and increased arginase activity compared to cells from CD36 + mice. L1 adipocytes treated with oxLDL showed time and dose dependent increases in CD36, activated JNK, inhibitory IRS‐1 serine phosphorylation, and adipocyte lypolysis with decreased glucose uptake. Pre‐incubation with either a CD36 mAb or JNK inhibitor attenuated these changes. In addition, adipocytes co‐cultured with transwell separation from CD36 − macrophages showed both decreased JNK and inhibitory IRS‐1 serine phosphorylation compared to those co‐cultured with CD36 + macrophages. These data suggest a CD36‐dependent paracrine loop between adipocytes and macrophages that facilitates chronic inflammation in adipose and underlies IR common to PA‐HL states.