Hematopoietic Cell–Restricted Deletion of CD36 Reduces High-Fat Diet–Induced Macrophage Infiltration and Improves Insulin Signaling in Adipose Tissue
- Hayley T. Nicholls1,2,
- Greg Kowalski1,2,
- David J. Kennedy3,
- Steve Risis1,
- Lee A. Zaffino1,2,
- Nadine Watson1,
- Peter Kanellakis4,
- Matthew J. Watt5,
- Alex Bobik4,
- Arend Bonen6,
- Maria Febbraio3,
- Graeme I. Lancaster1⇓ and
- Mark A. Febbraio1,2⇓
- 1Cellular and Molecular Metabolism Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- 2Department of Biochemistry and Molecular Biology, Monash University, Melbourne, Australia
- 3Department of Physiology, Monash University, Melbourne, Australia
- 4Vascular Biology and Atherosclerosis Laboratory, Baker IDI Heart and Diabetes Institute, Melbourne, Australia
- 5Department of Molecular Cardiology, Lerner Research Institute, Cleveland, Ohio
- 6Department of Human Health and Nutritional Sciences, University of Guelph, Ontario, Canada
- Corresponding author: Mark A. Febbraio, , or Graeme I. Lancaster, .
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.
This article contains Supplementary Data online at http://diabetes.diabetesjournals.org/lookup/suppl/doi:10.2337/db10-1353/-/DC1.
- Received October 3, 2010.
- Accepted January 24, 2011.
- © 2011 by the American Diabetes Association.
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