TY - JOUR AU - Nicholls, HT AU - Kowalski, G AU - Kennedy, DJ AU - Risis, S AU - Zaffino, LA AU - Watson, N AU - Kanellakis, P AU - Watt, MJ AU - Bobik, A AU - Bonen, A AU - Febbraio, M AU - Lancaster, GI AU - Febbraio, MA Y2 - 2020/12/09 Y1 - 2011/04/01 SN - 0012-1797 UR - http://hdl.handle.net/11343/253132 AB - OBJECTIVE: The fatty acid translocase and scavenger receptor CD36 is important in the recognition and uptake of lipids. Accordingly, we hypothesized that it plays a role in saturated fatty acid-induced macrophage lipid accumulation and proinflammatory activation. RESEARCH DESIGN AND METHODS: In vitro, the effect of CD36 inhibition and deletion in lipid-induced macrophage inflammation was assessed using the putative CD36 inhibitor, sulfosuccinimidyl oleate (SSO), and bone marrow-derived macrophages from mice with (CD36KO) or without (wild-type) global deletion of CD36. To investigate whether deletion of macrophage CD36 would improve insulin sensitivity in vivo, wild-type mice were transplanted with bone marrow from CD36KO or wild-type mice and then fed a standard or high-fat diet (HFD) for 20 weeks. RESULTS: SSO treatment markedly reduced saturated fatty acid-induced lipid accumulation and inflammation in RAW264.7 macrophages. Mice harboring CD36-specific deletion in hematopoietic-derived cells (HSC CD36KO) fed an HFD displayed improved insulin signaling and reduced macrophage infiltration in adipose tissue compared with wild-type mice, but this did not translate into protection against HFD-induced whole-body insulin resistance. Contrary to our hypothesis and our results using SSO in RAW264.7 macrophages, neither saturated fatty acid-induced lipid accumulation nor inflammation was reduced when comparing CD36KO with wild-type bone marrow-derived macrophages. CONCLUSIONS: Although CD36 does not appear important in saturated fatty acid-induced macrophage lipid accumulation, our study uncovers a novel role for CD36 in the migration of proinflammatory phagocytes to adipose tissue in obesity, with a concomitant improvement in insulin action. LA - English PB - AMER DIABETES ASSOC T1 - Hematopoietic Cell-Restricted Deletion of CD36 Reduces High-Fat Diet-Induced Macrophage Infiltration and Improves Insulin Signaling in Adipose Tissue DO - 10.2337/db10-1353 IS - Diabetes VL - 60 IS - 4 SP - 1100-1110 L1 - /bitstream/handle/11343/253132/PMC3064084.pdf?sequence=1&isAllowed=y ER -