载脂蛋白 AI 和高密度脂蛋白通过胆固醇转运蛋白：三磷酸腺苷结合盒转运蛋白 A1、三磷酸腺苷结合盒转运蛋白 G1 和清道夫受体 B1 对脂肪细胞具有抗炎作用。
Apolipoprotein AI and high-density lipoprotein have anti-inflammatory effects on adipocytes via cholesterol transporters: ATP-binding cassette A-1, ATP-binding cassette G-1, and scavenger receptor B-1.
机构信息
Department of Medicine, Division of Metabolism, Endocrinology, and Nutrition, University of Washington, Seattle, WA 98195, USA.
出版信息
Circ Res. 2013 May 10;112(10):1345-54. doi: 10.1161/CIRCRESAHA.111.300581. Epub 2013 Mar 15.
RATIONALE
Macrophage accumulation in adipose tissue associates with insulin resistance and increased cardiovascular disease risk. We previously have shown that generation of reactive oxygen species and monocyte chemotactic factors after exposure of adipocytes to saturated fatty acids, such as palmitate, occurs via translocation of NADPH oxidase 4 into lipid rafts (LRs). The anti-inflammatory effects of apolipoprotein AI (apoAI) and high-density lipoprotein (HDL) on macrophages and endothelial cells seem to occur via cholesterol depletion of LRs. However, little is known concerning anti-inflammatory effects of HDL and apoAI on adipocytes.
OBJECTIVE
To determine whether apoAI and HDL inhibit inflammation in adipocytes and adipose tissue, and whether this is dependent on LRs.
METHODS AND RESULTS
In 3T3L-1 adipocytes, apoAI, HDL, and methyl-β-cyclodextrin inhibited chemotactic factor expression. ApoAI and HDL also disrupted LRs, reduced plasma membrane cholesterol content, inhibited NADPH oxidase 4 translocation into LRs, and reduced palmitate-induced reactive oxygen species generation and monocyte chemotactic factor expression. Silencing ATP-binding cassette A-1 abrogated the effect of apoAI, but not HDL, whereas silencing ATP-binding cassette G-1 or scavenger receptor B-1 abrogated the effect of HDL but not apoAI. In vivo, apoAI transgenic mice fed a high-fat, high-sucrose, cholesterol-containing diet showed reduced chemotactic factor and proinflammatory cytokine expression and reduced macrophage accumulation in adipose tissue.
CONCLUSIONS
ApoAI and HDL have anti-inflammatory effects in adipocytes and adipose tissue similar to their effects in other cell types. These effects are consistent with disruption and removal of cholesterol from LRs, which are regulated by cholesterol transporters, such as ATP-binding cassette A-1, ATP-binding cassette G-1, and scavenger receptor B-1.
原理
脂肪组织中巨噬细胞的积累与胰岛素抵抗和增加心血管疾病风险有关。我们之前已经表明，脂肪细胞暴露于饱和脂肪酸（如棕榈酸）后，活性氧和单核细胞趋化因子的产生是通过 NADPH 氧化酶 4 易位到脂筏（LRs）中发生的。载脂蛋白 AI（apoAI）和高密度脂蛋白（HDL）对巨噬细胞和内皮细胞的抗炎作用似乎是通过 LRs 中的胆固醇耗竭发生的。然而，关于 HDL 和 apoAI 对脂肪细胞的抗炎作用知之甚少。
目的
确定 apoAI 和 HDL 是否抑制脂肪细胞和脂肪组织的炎症，以及这是否依赖于 LRs。
方法和结果
在 3T3L-1 脂肪细胞中，apoAI、HDL 和甲基-β-环糊精抑制趋化因子表达。apoAI 和 HDL 还破坏了 LRs，降低了质膜胆固醇含量，抑制了 NADPH 氧化酶 4 易位到 LRs，并减少了棕榈酸诱导的活性氧产生和单核细胞趋化因子表达。沉默 ATP 结合盒 A-1 消除了 apoAI 的作用，但不是 HDL，而沉默 ATP 结合盒 G-1 或清道夫受体 B-1 消除了 HDL 的作用，但不是 apoAI。在体内，喂食高脂肪、高蔗糖、含胆固醇饮食的 apoAI 转基因小鼠显示趋化因子和促炎细胞因子表达减少，脂肪组织中巨噬细胞积累减少。
结论
apoAI 和 HDL 在脂肪细胞和脂肪组织中具有抗炎作用，与它们在其他细胞类型中的作用相似。这些作用与胆固醇从 LRs 中的中断和去除一致，这些作用由胆固醇转运蛋白（如 ATP 结合盒 A-1、ATP 结合盒 G-1 和清道夫受体 B-1）调节。
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