Hematopoietic Cell-Restricted Deletion of CD36 Reduces High-Fat Diet-Induced Macrophage Infiltration and Improves Insulin Signaling in Adipose Tissue
AuthorNicholls, HT; Kowalski, G; Kennedy, DJ; Risis, S; Zaffino, LA; Watson, N; Kanellakis, P; Watt, MJ; Bobik, A; Bonen, A; ...
PublisherAMER DIABETES ASSOC
University of Melbourne Author/sWatt, Matthew
Document TypeJournal Article
CitationsNicholls, H. T., Kowalski, G., Kennedy, D. J., Risis, S., Zaffino, L. A., Watson, N., Kanellakis, P., Watt, M. J., Bobik, A., Bonen, A., Febbraio, M., Lancaster, G. I. & Febbraio, M. A. (2011). Hematopoietic Cell-Restricted Deletion of CD36 Reduces High-Fat Diet-Induced Macrophage Infiltration and Improves Insulin Signaling in Adipose Tissue. DIABETES, 60 (4), pp.1100-1110. https://doi.org/10.2337/db10-1353.
Access StatusOpen Access
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.
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