Ntambi James M, Miyazaki Makoto
Departments of Biochemistry and Nutritional Sciences, University of Wisconsin, Madison, Wisconsin 53706, USA.
Curr Opin Lipidol. 2003 Jun;14(3):255-61. doi: 10.1097/00041433-200306000-00005.
Stearoyl-Coenzyme A (CoA) desaturase is a central lipogenic enzyme catalyzing the synthesis of monounsaturated fatty acids - mainly oleate (C(18:1)). Oleate is the most abundant monounsaturated fatty acid in dietary fat and is therefore readily available. Why, then, is stearoyl-CoA desaturase a highly regulated enzyme? This review summarizes the recent and timely advances concerning the important role of stearoyl-CoA desaturase in metabolism.
Recent findings using mice that have a naturally occurring mutation in the SCD1 gene isoform as well as a mouse model with a targeted disruption of the stearoyl-CoA desaturase gene-1 (SCD1-/-) have revealed the role of de-novo synthesized oleate and thus the physiological importance of SCD1 expression. In the highlighted references, it is shown that the SCD1-/- mice have reduced body adiposity, increased insulin sensitivity, and are resistant to diet-induced obesity. The expression of several genes of lipid oxidation is upregulated, whereas lipid synthesis genes are downregulated. SCD1 was also found to be a component of the novel metabolic response to the hormone leptin.
SCD1, therefore, appears to be an important metabolic control point, and inhibition of its expression could be of benefit for the treatment of obesity, diabetes and other metabolic diseases.
硬脂酰辅酶A去饱和酶是一种核心的脂肪生成酶,催化单不饱和脂肪酸的合成——主要是油酸(C(18:1))。油酸是膳食脂肪中最丰富的单不饱和脂肪酸,因此很容易获得。那么,为什么硬脂酰辅酶A去饱和酶是一种受到高度调控的酶呢?本综述总结了关于硬脂酰辅酶A去饱和酶在代谢中重要作用的最新进展。
利用在SCD1基因亚型中存在自然突变的小鼠以及硬脂酰辅酶A去饱和酶基因-1(SCD1-/-)靶向敲除的小鼠模型进行的最新研究揭示了从头合成的油酸的作用,从而也揭示了SCD1表达的生理重要性。在重点参考文献中表明,SCD1-/-小鼠的体脂减少、胰岛素敏感性增加,并且对饮食诱导的肥胖具有抗性。几种脂质氧化基因的表达上调,而脂质合成基因的表达下调。还发现SCD1是对激素瘦素的新型代谢反应的一个组成部分。
因此,SCD1似乎是一个重要的代谢控制点,抑制其表达可能有益于肥胖症、糖尿病和其他代谢性疾病的治疗。