文章基本信息

标题：Mechanism of hypertriglyceridemia in CTP:phosphoethanolamine cytidylyltransferase-deficient mice
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作者：Ratnesh Kumar Singh ; Morgan D. Fullerton ; Donna Vine 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2012
卷号：53
期号：9
页码：1811-1822
DOI：10.1194/jlr.M021881
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：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, apoB-100, 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.
关键词：phospholipid ; very low density lipoprotein secretion ; chylomicron formation ; triglyceride