Hematopoietic Cell–Restricted Deletion of CD36 Reduces High-Fat Diet–Induced Macrophage Infiltration and Improves Insulin Signaling in Adipose Tissue Article (Web of Science)

abstract

  • 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.

authors

  • Nicholls, Hayley T.
  • Kowalski, Greg
  • Kennedy, David J
  • Risis, Steve
  • Zaffino, Lee A.
  • Watson, Nadine
  • Kanellakis, Peter
  • Watt, Matthew J.
  • Bobik, Alex
  • Bonen, Arend
  • Febbraio, Maria
  • Lancaster, Graeme I.
  • Febbraio, Mark A.

publication date

  • 2011

webpage

published in

number of pages

  • 10

start page

  • 1100

end page

  • 1110

volume

  • 60

issue

  • 4