Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia
Relationship between stearoyl-CoA desaturase activity and plasma triglycerides in human and mouse hypertriglyceridemia
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DOI：
10.1194/jlr.m200189-jlr200
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发表时间：
2002-11-01
影响因子：
6.5
通讯作者：
Ntambi, JM
中科院分区：
文献类型：
--
作者：
Attie, AD;Krauss, RM;Ntambi, JM
硬脂酰辅酶A去饱和酶（SCD）在人体的一些组织中高水平表达，是油酸（18:1）和棕榈油酸（16:1）生物合成所必需的。这些单不饱和脂肪酸是磷脂、甘油三酯、蜡酯和胆固醇酯的主要成分。SCD I基因靶向破坏的小鼠极低密度脂蛋白（VLDL）水平非常低，甘油三酯和胆固醇酯的生物合成受损。在高血脂模型HYPLIP小鼠中，肝脏SCD活性增加4倍，去饱和指数增加1.8倍，血浆甘油三酯增加2倍。我们使用18:1/18:0的血浆比值（“去饱和指数”）作为人体中SCD活性的体内测量指标。在甘油三酯范围从0.3到20 mM的人体受试者中，去饱和比值占血浆甘油三酯水平变异的三分之一。去饱和指数增加2倍与血浆甘油三酯增加4倍相关。在接受高碳水化合物饮食的人体受试者中，去饱和指数解释了甘油三酯变异的44%。我们提出，许多影响血浆甘油三酯水平的因素是通过汇聚于对SCD活性的调节来实现的。
Stearoyl-CoA desaturase (SCD) is expressed at high levels in several human tissues and is required for the biosynthesis of oleate (18:1) and palmitoleate (16:1). These monounsaturated fatty acids are the major components of phospholipids, triglycerides, wax esters, and cholesterol esters. Mice with a targeted disruption of the SCD I gene have very low levels of VLDL and impaired triglyceride and cholesterol ester biosynthesis. In the HYPLIP mouse, a model of hyperlipidemia, there was a 4-fold increase in hepatic SCD activity, a 1.8-fold increase in the desaturation index, and a 2-fold increase in plasma triglycerides. We used the plasma ratio of 18:1/18:0 (the "desaturation index") as an in vivo measure of SCD activity in human subjects. In human subjects with triglycerides ranging from 0.3 to 20 mM, the desaturation ratio accounted for one-third of the variance in plasma triglyceride levels. A 2-fold increase in the desaturation index was associated with a 4-fold increase in plasma triglycerides. In human subjects exposed to a high carbohydrate diet, the desaturation index explained 44% of the variance in triglycerides. We propose that many of the factors that influence plasma triglyceride levels do so by converging upon the regulation of SCD activity.