Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss
Role for stearoyl-CoA desaturase-1 in leptin-mediated weight loss
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DOI：
10.1126/science.1071527
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发表时间：
2002-07-12
期刊：
影响因子：
56.9
通讯作者：
Friedman, JM
中科院分区：
文献类型：
--
作者：
Cohen, P;Miyazaki, M;Friedman, JM
瘦素引起的代谢反应不能单独用它的厌食作用来解释。为了研究瘦素代谢作用的机制，我们使用转录技术鉴定了ob/ob肝脏中瘦素调节基因。瘦素被发现特异性抑制肝硬脂酰辅酶a去饱和酶1 （SCD-1）的RNA水平和酶活性，SCD-1催化单不饱和脂肪酸的生物合成。缺乏SCD-1的小鼠瘦且高代谢。SCD-1基因突变的ob/ob小鼠的肥胖程度明显低于ob/ob对照组，并且能量消耗明显增加。SCD-1突变的ob/ob小鼠肝脏组织学正常，甘油三酯储存和VLDL（极低密度脂蛋白）产生显著降低。这些发现表明，SCD-1的下调是瘦素代谢作用的重要组成部分。
Leptin elicits a metabolic response that cannot be explained by its anorectic effects alone. To examine the mechanism underlying leptin's metabolic actions, we used transcription pro ling to identify leptin-regulated genes in ob/ob liver. Leptin was found to specifically repress RNA levels and enzymatic activity of hepatic stearoyl-CoA desaturase-1 (SCD-1), which catalyzes the biosynthesis of monounsaturated fatty acids. Mice lacking SCD-1 were lean and hypermetabolic. ob/ob mice with mutations in SCD-1 were significantly less obese than ob/ob controls and had markedly increased energy expenditure. ob/ob mice with mutations in SCD-1 had histologically normal livers with significantly reduced triglyceride storage and VLDL ( very low density lipoprotein) production. These findings suggest that down-regulation of SCD-1 is an important component of leptin's metabolic actions.