Poudyal Hemant, Brown Lindsay
School of Biomedical Sciences, The University of Queensland, Australia.
Endocr Metab Immune Disord Drug Targets. 2011 Sep 1;11(3):217-31. doi: 10.2174/187153011796429826.
Stearoyl-CoA desaturase 1 (SCD-1) is the rate-limiting enzyme that catalyses the conversion of saturated to monounsaturated fatty acids. Increased SCD-1 expression and activity has been implicated in cancer, cardiovascular diseases, insulin resistance and obesity. Studies with humans, wild-type rodents, knock-out mice and cells in culture show that SCD-1 inhibition decreases lipogenesis and increases GLUT4-mediated glucose uptake in skeletal muscle. In this review, we will evaluate the role of SCD-1 as a homeostatic check-point between glucose and fatty acid metabolism in the development and progression of obesity. In addition to the role of SCD-1 in glucose and fatty acid metabolism, we will also discuss the expression and regulation of SCD-1, its specific interactions with inflammatory responses and PPARs, the role of SCD-1 derived MUFAs in obesity and the relevance of SCD desaturation index as a predictor of obesity and metabolic syndrome. Additionally, we will explore the prospects of SCD-1 as a potential drug target for the management of obesity and related disorders.
硬脂酰辅酶A去饱和酶1(SCD-1)是催化饱和脂肪酸转化为单不饱和脂肪酸的限速酶。SCD-1表达和活性的增加与癌症、心血管疾病、胰岛素抵抗和肥胖有关。对人类、野生型啮齿动物、基因敲除小鼠和培养细胞的研究表明,抑制SCD-1可减少脂肪生成,并增加骨骼肌中GLUT4介导的葡萄糖摄取。在这篇综述中,我们将评估SCD-1作为肥胖发生和发展过程中葡萄糖和脂肪酸代谢之间的稳态检查点的作用。除了SCD-1在葡萄糖和脂肪酸代谢中的作用外,我们还将讨论SCD-1的表达和调控、其与炎症反应和过氧化物酶体增殖物激活受体(PPARs)的特异性相互作用、SCD-1衍生的单不饱和脂肪酸在肥胖中的作用以及SCD去饱和指数作为肥胖和代谢综合征预测指标的相关性。此外,我们将探讨SCD-1作为肥胖及相关疾病管理的潜在药物靶点的前景。