A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling.
A CD36-dependent pathway enhances macrophage and adipose tissue inflammation and impairs insulin signalling.
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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。
DOI：
10.1093/cvr/cvq360
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发表时间：
2011-02-15
影响因子：
10.8
通讯作者：
Febbraio M
中科院分区：
文献类型：
--
作者：
Kennedy DJ;Kuchibhotla S;Westfall KM;Silverstein RL;Morton RE;Febbraio M
肥胖和肥胖症与胰岛素抵抗（IR）有关;然而，其机制仍不完全清楚。促动脉粥样硬化性高脂血症状态的特征在于炎症、氧化应激和病理生理氧化脂质，包括清道夫受体CD 36的配体。在这里，我们测试的假设，即缺乏CD 36保护小鼠从IR与饮食诱导的肥胖和肥胖症。来自CD 36 −/−小鼠的脂肪组织表现出较少的炎症表型，并在体内以及脂肪细胞和巨噬细胞水平上改善了胰岛素信号传导。病理生理配体氧化低密度脂蛋白（oxLDL）激活c-Jun N-末端激酶（JNK），并以CD 36依赖性方式破坏脂肪细胞和巨噬细胞中的胰岛素信号传导。与野生型巨噬细胞相比，从高脂饮食喂养后的CD 36 −/−小鼠中分离的巨噬细胞在共培养后引起脂肪细胞中JNK活化和胰岛素信号传导抑制较少。这些数据表明，脂肪细胞和巨噬细胞之间的CD 36依赖性炎性旁分泌环促进慢性炎症，并导致肥胖和血脂异常中常见的IR。
Obesity and hyperlipidaemia are associated with insulin resistance (IR); however, the mechanisms responsible remain incompletely understood. Pro-atherogenic hyperlipidaemic states are characterized by inflammation, oxidant stress, and pathophysiologic oxidized lipids, including ligands for the scavenger receptor CD36. Here we tested the hypothesis that the absence of CD36 protects mice from IR associated with diet-induced obesity and hyperlipidaemia. Adipose tissue from CD36−/− mice demonstrated a less inflammatory phenotype and improved insulin signalling in vivo and at the level of the adipocyte and macrophage. The pathophysiologic ligand oxidized low-density lipoprotein (oxLDL) activated c-Jun N-terminal kinase (JNK) and disrupted insulin signalling in both adipocytes and macrophages in a CD36-dependent manner. Macrophages isolated from CD36−/− mice after high-fat diet feeding elicited less JNK activation and inhibition of insulin signalling in adipocytes after co-culture compared with wild-type macrophages. These data suggest that a CD36-dependent inflammatory paracrine loop between adipocytes and macrophages facilitates chronic inflammation and contributes to IR common in obesity and dyslipidaemia.
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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：
120.7
作者：
Holvoet, Paul;Lee, Duk-Hee;Jacobs, David R., Jr.
通讯作者：
Jacobs, David R., Jr.
影响因子：
4.4
作者：
Martin-Fuentes, Paula;Civeira, Fernando;Cenarro, Ana
通讯作者：
Cenarro, Ana
影响因子：
4.3
作者：
Bassaganya-Riera, Josep;Misyak, Sarah;Hontecillas, Raquel
通讯作者：
Hontecillas, Raquel
影响因子：
6.5
作者：
Goudriaan, JR;Dahlmans, VEH;Voshol, PJ
通讯作者：
Voshol, PJ