Regulation of Stearoyl-CoA desaturase expression
Regulation of Stearoyl-CoA desaturase expression
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DOI：
10.1007/s11745-004-1331-2
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发表时间：
2004-11-01
期刊：
影响因子：
1.9
通讯作者：
Dobrzyn, A
中科院分区：
文献类型：
--
作者：
Ntambi, JM;Miyazaki, A;Dobrzyn, A
硬脂酰辅酶a去饱和酶（SCD）是一种脂肪生成的调节酶，催化单不饱和脂肪酸从头合成的限速步骤，主要是由硬脂酰辅酶a和棕榈酰辅酶a合成油酸酯和棕榈油酸酯。油酸和棕榈油酸是膜磷脂、甘油三酯、蜡酯、胆固醇酯和烷基二酰基甘油的主要单不饱和脂肪酸。几种SCD基因亚型（SCD1、SCD2、SCD3和SCD4）存在于小鼠中，其中两种已在人类中被鉴定。肝细胞中SCD1基因的表达受多种刺激因素的调控，包括饮食和激素。我们感兴趣的是为什么SCD是一种高度调控的酶，尽管这种酶的主要产物油酸是饮食中最丰富的FA之一，因此很容易获得。饮食中的油酸也因其降低tg的作用而闻名，作为橄榄油的主要成分，预计会有有益的效果。然而，在一些动物模型中，高SCD活性与糖尿病、肥胖、动脉粥样硬化和癌症有关；因此，必须仔细评估新生油酸盐在这些疾病状态中所起的作用。通过使用组织油酸缺乏的SCD1-/-小鼠，我们开始更多地了解SCD基因表达和油酸在正常和疾病状态下的生理作用。
Stearoyl-COA desaturase (SCD) is a regulatory enzyme in lipogenesis, catalyzing the rate-limiting step in the overall de novo synthesis of monounsaturated FA, mainly oleate and palmitoleate from stearoyl- and palmitoyl-CoA, respectively. Oleate and palmitoleate are the major monounsaturated FA of membrane phospholipids, TG, wax esters, cholesterol esters, and alkyldiacylglycerol. Several SCD gene isoforms (SCD1, SCD2, SCD3, and SCD4) exist in mice, and two have been characterized in humans. SCD1 gene expression in liver cells is regulated by numerous stimuli including diet and hormones. We are interested in why SCD is such a highly regulated enzyme even though oleate, the major product of this enzyme, is one of the most abundant FA in the diet and is therefore readily available. Dietary oleate is also well known for its TG-lowering effects and, as a major component of olive oil, is expected to have beneficial effects. However, high SCD activity has been implicated in diabetes, obesity, atherosclerosis, and cancer in several animal models; therefore, the role that de novo oleate plays in these disease states has to be carefully evaluated. By using SCD1-/- mice, which are deficient in tissue oleate, we begin to learn more about the physiological role of SCD gene expression and oleate in normal and disease states.