Expression of the human apoE2 isoform in adipocytes: altered cellular processing and impaired adipocyte lipogenesis
Expression of the human apoE2 isoform in adipocytes: altered cellular processing and impaired adipocyte lipogenesis
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DOI：
10.1194/jlr.m017160
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发表时间：
2011-09-01
影响因子：
6.5
通讯作者：
Mazzone, Theodore
中科院分区：
文献类型：
--
作者：
Huang, Zhi H.;Maeda, Nobuyo;Mazzone, Theodore
载脂蛋白E在脂肪细胞中的表达被证明在调节脂肪细胞甘油三酯代谢和基因表达方面具有重要作用，这种作用不依赖于循环和细胞外的载脂蛋白E。使用从人APOE2、-3和-4敲入小鼠获得的脂肪细胞，评估了常见的人类apoE亚型对脂肪细胞表达的影响。APOE2亚型的表达与脂肪细胞apoE基因表达和apoE合成增加有关。新合成的APOE2在脂肪细胞中不稳定，表现为降解增加和分泌减少。与apoE3小鼠相比，表达APOE2的小鼠具有高脂血症，并且性腺脂肪垫和脂肪细胞的大小增加。然而，在分离的细胞中，表达APOE2亚型会导致脂肪生成缺陷，并增加甘油三酯的水解率。脂肪组织与含有apoE3的富含TG的脂蛋白孵育后，apoE3和-E4小鼠的脂肪组织中的甘油三酯显著增加，但APOE2小鼠没有。作为生脂底物的FFA内化能力降低是导致脂肪生成缺陷的原因。新合成的APOE2在脂肪细胞中不稳定，导致脂肪细胞TG合成减少和FA摄取缺陷。这些变化概括了在apoE基因敲除脂肪细胞中观察到的变化，并对理解表达E2亚型的人类的代谢障碍有意义。人APOE2亚型在脂肪细胞中的表达：细胞加工改变和脂肪细胞脂肪生成受损。J.Lipid Res.2011年。52：1733-1741。
Expression of apoE in adipocytes has been shown to have an important role in modulating adipocyte triglyceride (TG) metabolism and gene expression that is independent of circulating and extracellular apoE. The impact of adipocyte expression of common human apoE isoforms was evaluated using adipocytes harvested from human apoE2, -3, and -4 knock-in mice. Expression of the apoE2 isoform was associated with an increase in adipocyte apoE gene expression and apoE synthesis. Newly synthesized apoE2 was unstable in adipocytes and demonstrated increased degradation and decreased secretion. ApoE2-expressing mice were hyperlipidemic, and had increased size of gonadal fat pads and of adipocytes, compared with apoE3 mice. In isolated cells, however, expression of the apoE2 isoform produced defective lipogenesis and increased TG hydrolysis. Incubation of adipose tissue with apoE3-containing TG-rich lipoproteins resulted in a significant increase in TG in adipose tissue from apoE3 and -E4 mice, but not apoE2 mice. Reduced capacity to internalize FFA as lipogenic substrate contributed to defective lipogenesis. Newly synthesized apoE2 is unstable in adipocytes and results in decreased adipocyte TG synthesis and defective FA uptake. These changes recapitulate those observed in apoE knockout adipocytes and have implications for understanding metabolic disturbances in humans expressing the E2 isoform.-Huang, Z. H., N. Maeda, and T. Mazzone. Expression of the human apoE2 isoform in adipocytes: altered cellular processing and impaired adipocyte lipogenesis. J. Lipid Res. 2011. 52: 1733-1741.