Hematopoietic cell-restricted deletion of CD36 reduces high-fat diet-induced macrophage infiltration and improves insulin signaling in adipose tissue.
Hematopoietic cell-restricted deletion of CD36 reduces high-fat diet-induced macrophage infiltration and improves insulin signaling in adipose tissue.
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造血细胞限制性删除 CD36 可减少高脂饮食诱导的巨噬细胞浸润，并改善脂肪组织中的胰岛素信号传导。
DOI：
10.2337/db10-1353
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发表时间：
2011-04
期刊：
影响因子：
7.7
通讯作者：
Febbraio MA
中科院分区：
文献类型：
--
作者：
Nicholls HT;Kowalski G;Kennedy DJ;Risis S;Zaffino LA;Watson N;Kanellakis P;Watt MJ;Bobik A;Bonen A;Febbraio M;Lancaster GI;Febbraio MA
脂肪酸转位酶和清道夫受体 CD36 对于脂质的识别和摄取很重要。因此，我们假设它在饱和脂肪酸诱导的巨噬细胞脂质积累和促炎激活中发挥作用。在体外，使用假定的 CD36 抑制剂、磺基琥珀酰亚胺油酸酯 (SSO) 和来自具有 (CD36KO) 或不具有 (野生型) CD36 整体删除的小鼠的骨髓来源的巨噬细胞，评估了 CD36 抑制和删除对脂质诱导的巨噬细胞炎症的影响。为了研究巨噬细胞CD36的缺失是否会改善体内胰岛素敏感性，将CD36KO或野生型小鼠的骨髓移植到野生型小鼠中，然后喂食标准或高脂肪饮食（HFD）20周。 SSO 治疗显着减少了 RAW264.7 巨噬细胞中饱和脂肪酸诱导的脂质积累和炎症。与野生型小鼠相比，造血源性细胞中含有 CD36 特异性缺失 (HSC CD36KO) 的小鼠，与野生型小鼠相比，饲喂 HFD 后胰岛素信号传导得到改善，脂肪组织中巨噬细胞浸润减少，但这并不能转化为针对 HFD 诱导的全身胰岛素抵抗的保护作用。与我们的假设和我们在 RAW264.7 巨噬细胞中使用 SSO 的结果相反，当将 CD36KO 与野生型骨髓来源的巨噬细胞进行比较时，饱和脂肪酸诱导的脂质积累和炎症均没有减少。尽管 CD36 在饱和脂肪酸诱导的巨噬细胞脂质积累中似乎并不重要，但我们的研究揭示了 CD36 在肥胖症中促炎吞噬细胞迁移到脂肪组织中的新作用，并伴随着胰岛素作用的改善。
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. 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. 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. 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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影响因子：
64.8
作者：
Hoebe, K;Georgel, P;Beutler, B
通讯作者：
Beutler, B
影响因子：
82.9
作者：
Arkan, MC;Hevener, AL;Karin, M
通讯作者：
Karin, M
CD36依赖性途径增强了巨噬细胞和脂肪组织炎症并损害胰岛素信号传导。
影响因子：
10.8
作者：
Kennedy DJ;Kuchibhotla S;Westfall KM;Silverstein RL;Morton RE;Febbraio M
通讯作者：
Febbraio M
影响因子：
6.5
作者：
Goudriaan, JR;Dahlmans, VEH;Voshol, PJ
通讯作者：
Voshol, PJ
DOI：
10.1016/j.bbrc.2009.12.050
发表时间：
2010-01-15
影响因子：
3.1
作者：
Drahota, Zdenek;Vrbacky, Marek;Houstek, Josef
通讯作者：
Houstek, Josef