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  -