代谢综合症是对一系列脂蛋白异常情况的总称，如：高血压、肥胖症、胰岛素抵抗，以及会导致心脏病和糖尿病风险的胆固醇过高。具有高胆固醇遗传性患病风险的人（家族性高血脂或FH）特别容易罹患代谢综合症。但是研究者们最近发现，阻断硬脂酰CoA去饱和酶1（SCD1）能够在很大程度上缓解患有代谢综合症的FH小鼠的症状。SCD1是一种帮助合成不饱和脂肪酸的酶。
以前的SCD1小鼠实验发现，在正常小鼠中阻断这种酶能够减少肥胖；Michael Hayden及其同事猜测，这种保护机制可能也能对小鼠胆固醇水平过高起作用。
他们在小鼠中通过敲除LDL受体以模拟FH，由此累积胆固醇。当给小鼠饲以高脂肪食料时，这些小鼠在成年后出现肥胖和糖尿病等疾病。但是，当研究者把SCD1也敲除时，小鼠的状况明显改善，肝脏中积聚的脂肪急剧减少，这使血液中的甘油三酸酯含量也相应减少，并提高了对胰岛素的灵敏度，减少体重增加。这些结果表明，SCD1对代谢综合症中生成其它成分的FH个体来说可能是一种潜在的药物靶标。
相关论文发表于2008年1月份的《油脂研究期刊》（Journal of Lipid Research，JLR）。
生物谷推荐原始出处：
Journal of Lipid Research, Vol. 49, 217-229, January 2008
Copyright © 2008 by American Society for Biochemistry and Molecular Biology
Absence of stearoyl-CoA desaturase-1 ameliorates features of the metabolic syndrome in LDLR-deficient mice
Marcia L. E. MacDonald*, Roshni R. Singaraja*, Nagat Bissada*, Piers Ruddle*, Russell Watts, Joanna M. Karasinska*, William T. Gibson*, Catherine Fievet,**,, Jean E. Vance, Bart Staels,**, and Michael R. Hayden1,*
* Centre for Molecular Medicine and Therapeutics, Department of Medical Genetics, University of British Columbia, and Child and Family Research Institute, Vancouver, British Columbia, Canada V5Z 4H4
Canadian Institutes of Health Research Group on the Molecular and Cell Biology of Lipids, Department of Medicine, University of Alberta, Edmonton, Alberta, Canada T6G 2S2
Institut Pasteur de Lille, Département d'Athérosclérose, Lille, F-59019 France
** Institut National de la Santé et de la Recherche Médicale U545, Lille, F-59019 France
Université de Lille 2, Lille, F-59006 France
Published, JLR Papers in Press, October 24, 2007.
1 To whom correspondence should be addressed. e-mail: mrh@cmmt.ubc.ca
A combination of the interrelated metabolic risk factors obesity, insulin resistance, dyslipidemia, and hypertension, often described as the "metabolic syndrome," is known to increase the risk of developing cardiovascular disease and diabetes. Stearoyl-coenzyme A desaturase (SCD) activity has been implicated in the metabolic syndrome, but detailed studies of the beneficial metabolic effects of SCD deficiency have been limited. Here, we show that absence of the Scd1 gene product reduces plasma triglycerides and reduces weight gain in severely hyperlipidemic low density lipoprotein receptor (LDLR)-deficient mice challenged with a Western diet. Absence of SCD1 also increases insulin sensitivity, as measured by intraperitoneal glucose and insulin tolerance testing. SCD1 deficiency dramatically reduces hepatic lipid accumulation while causing more modest reductions in plasma apolipoproteins, suggesting that in conditions of sustained hyperlipidemia, SCD1 functions primarily to mediate lipid stores. In addition, absence of SCD1 partially ameliorates the undesirable hypertriglyceridemic effect of antiatherogenic liver X receptor agonists. Our results demonstrate that constitutive reduction of SCD activity improves the metabolic phenotype of LDLR-deficient mice on a Western diet.
Supplementary key words monounsaturated fatty acids • very low density lipoprotein • high density lipoprotein • apolipoprotein B • mouse model • liver • atherosclerosis • ATP binding cassette transporter A1 • hyperlipidemia • Western diet • low density lipoprotein receptor • coenzyme A
Abbreviations: ACC-1, acetyl-coenzyme A carboxylase-1; apoE, apolipoprotein E; FH, familial hypercholesterolemia; FPLC, fast-protein liquid chromatography; HTG, hypertriglyceridemia; LDLR, low density lipoprotein receptor; LXR, liver X receptor; SCD, stearoyl-coenzyme A desaturase; SREBP-1, sterol-regulatory element binding protein-1; TC, total cholesterol; TG, triglyceride
