Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity.
Scavenger receptor CD36 expression contributes to adipose tissue inflammation and cell death in diet-induced obesity.
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DOI：
10.1371/journal.pone.0036785
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
van der Westhuyzen DR
中科院分区：
文献类型：
--
作者：
Cai L;Wang Z;Ji A;Meyer JM;van der Westhuyzen DR
肥胖症中增大的脂肪组织的特征是炎症，包括巨噬细胞和淋巴细胞的募集和浸润。本研究的目的是探讨清道夫受体 CD36 在高脂肪饮食引起的肥胖以及脂肪组织炎症和细胞死亡中的作用。比较了喂养高脂肪饮食（60% kcal脂肪）16周的CD36缺陷（CD36 KO）小鼠和野生型（WT）小鼠的肥胖和脂肪组织炎症，并研究了从CD36 KO和WT小鼠分离的原代脂肪细胞和巨噬细胞的炎症反应。与WT小鼠相比，高脂肪饮食喂养的CD36 KO小鼠表现出肥胖和脂肪组织炎症减少，脂肪细胞死亡、促炎细胞因子表达以及巨噬细胞和T细胞积累减少。在原代细胞培养物中，巨噬细胞中 CD36 表达的缺失会降低脂多糖 (LPS) 响应的促炎细胞因子、促凋亡和 ER 应激基因表达。同样，原代脂肪细胞中 CD36 的缺乏会减少响应 LPS 的促炎细胞因子和趋化因子的分泌。原代巨噬细胞和脂肪细胞共培养实验表明，这些细胞类型在对 LPS 的炎症反应中协同作用，并且 CD36 调节这种协同效应。 CD36 通过在巨噬细胞和脂肪细胞中表达，增强饮食诱导的肥胖症中的脂肪组织炎症和细胞死亡。
The enlarged adipose tissue in obesity is characterized by inflammation, including the recruitment and infiltration of macrophages and lymphocytes. The objective of this study was to investigate the role of the scavenger receptor CD36 in high fat diet-induced obesity and adipose tissue inflammation and cell death. Obesity and adipose tissue inflammation was compared in CD36 deficient (CD36 KO) mice and wild type (WT) mice fed a high fat diet (60% kcal fat) for 16 weeks and the inflammatory response was studied in primary adipocytes and macrophages isolated from CD36 KO and WT mice. Compared to WT mice, CD36 KO mice fed a high fat diet exhibited reduced adiposity and adipose tissue inflammation, with decreased adipocyte cell death, pro-inflammatory cytokine expression and macrophage and T-cell accumulation. In primary cell culture, the absence of CD36 expression in macrophages decreased pro-inflammatory cytokine, pro-apoptotic and ER stress gene expression in response to lipopolysaccharide (LPS). Likewise, CD36 deficiency in primary adipocytes reduced pro-inflammatory cytokine and chemokine secretion in response to LPS. Primary macrophage and adipocyte co-culture experiments showed that these cell types act synergistically in their inflammatory response to LPS and that CD36 modulates such synergistic effects. CD36 enhances adipose tissue inflammation and cell death in diet-induced obesity through its expression in both macrophages and adipocytes.