Mechanism of hypertriglyceridemia in CTP: phosphoethanolamine cytidylyltransferase-deficient mice
Mechanism of hypertriglyceridemia in CTP: phosphoethanolamine cytidylyltransferase-deficient mice
复制标题
DOI：
10.1194/jlr.m021881
复制
发表时间：
2012-09-01
影响因子：
6.5
通讯作者：
Bakovic, Marica
中科院分区：
文献类型：
--
作者：
Singh, Ratnesh Kumar;Fullerton, Morgan D.;Bakovic, Marica
磷脂酰乙醇胺是一种重要的内叶磷脂，CTP：磷酸乙醇胺胞苷酰转移酶-Pcyt2是乙醇胺和二酰甘油从头合成磷脂酰乙醇胺的主要调节因子。小鼠 Pcyt2 基因的完全缺失会导致胚胎死亡，单等位基因缺陷会导致代谢综合征表型的发展，包括肝脂肪变性、高甘油三酯血症、肥胖和胰岛素抵抗。本研究旨在明确阐明Pcyt2杂合小鼠（Pcyt2（+/-））高甘油三酯血症的机制。这里的证据表明，与 8 周龄小鼠不同，32 周和 42 周龄 Pcyt2(+/-) 小鼠的 VLDL 分泌和肝微粒体甘油三酯转移蛋白活性增加。老年 Pcyt2(+/-) 小鼠还表现出餐后血浆 TAG 水平增加，负责肠道脂质吸收、运输和乳糜微粒分泌的基因刺激增加，血浆 Angptl4、apoB100 和 apoB-48 含量显着升高。此外，相对于对照同窝小鼠，Pcyt2(+/-) 小鼠在脂质攻击后血浆 HL 和 LPL 活性以及 TAG 清除率显着降低。总的来说，这些结果表明，伴随 Pcyt2 缺乏的高甘油三酯血症是多种代谢适应的结果，包括肝脏和肠道脂蛋白分泌升高，刺激参与脂质吸收和转运以及脂蛋白组装的基因的表达和/或活性，以及血浆 TAG 清除率和外周组织利用率降低。-Singh、R.K.、M.D. Fullerton、D. Vine 和 M. Bakovic。 CTP 高甘油三酯血症的机制：磷酸乙醇胺胞苷酰转移酶缺陷小鼠。 J.脂质研究。 2012。53：1811-1822。
Phosphatidylethanolamine is an important inner-leaflet phospholipid, and CTP:phosphoethanolamine cytidylyltransferase-Pcyt2 acts as the main regulator of the de novo phosphatidylethanolamine synthesis from ethanolamine and diacylglycerol. Complete deletion of the mouse Pcyt2 gene is embryonic lethal, and the single-allele deficiency leads to development of the metabolic syndrome phenotype, including liver steatosis, hypertriglyceridemia, obesity, and insulin resistance. This study aimed to specifically elucidate the mechanisms of hypertriglyceridemia in Pcyt2 heterozygous mice (Pcyt2(+/-)). Evidence here shows that unlike 8 week-old mice, 32 week-and 42 week-old Pcyt2(+/-) mice experience increased VLDL secretion and liver microsomal triglyceride transfer protein activity. Older Pcyt2(+/-) mice also demonstrate increased levels of postprandial plasma TAGs, increased stimulation of genes responsible for intestinal lipid absorption, transport and chylomicron secretion, and dramatically elevated plasma Angptl4, apoB100, and apoB-48 content. In addition, plasma HL and LPL activities and TAG clearance following a lipid challenge were significantly reduced in Pcyt2(+/-) mice relative to control littermates. Collectively, these results establish that the hypertriglyceridemia that accompanies Pcyt2 deficiency is the result of multiple metabolic adaptations, including elevated hepatic and intestinal lipoprotein secretion and stimulated expression and/or activity of genes involved in lipid absorption and transport and lipoprotein assembly, together with reduced plasma TAG clearance and utilization with peripheral tissues.-Singh, R. K., M. D. Fullerton, D. Vine, and M. Bakovic. Mechanism of hypertriglyceridemia in CTP: phosphoethanolamine cytidylyltransferase-deficient mice. J. Lipid Res. 2012. 53: 1811-1822.