代謝綜合癥是對一系列脂蛋白異常情況的總稱,，如：高血壓,、肥胖癥,、胰島素抵抗,，以及會導(dǎo)致心臟病和糖尿病風(fēng)險的膽固醇過高。具有高膽固醇遺傳性患病風(fēng)險的人（家族性高血脂或FH）特別容易罹患代謝綜合癥,。但是研究者們最近發(fā)現(xiàn),，阻斷硬脂酰CoA去飽和酶1（SCD1）能夠在很大程度上緩解患有代謝綜合癥的FH小鼠的癥狀。SCD1是一種幫助合成不飽和脂肪酸的酶,。
以前的SCD1小鼠實驗發(fā)現(xiàn),，在正常小鼠中阻斷這種酶能夠減少肥胖；Michael Hayden及其同事猜測,，這種保護機制可能也能對小鼠膽固醇水平過高起作用,。
他們在小鼠中通過敲除LDL受體以模擬FH，由此累積膽固醇,。當(dāng)給小鼠飼以高脂肪食料時,，這些小鼠在成年后出現(xiàn)肥胖和糖尿病等疾病。但是,，當(dāng)研究者把SCD1也敲除時,，小鼠的狀況明顯改善，肝臟中積聚的脂肪急劇減少,，這使血液中的甘油三酸酯含量也相應(yīng)減少,，并提高了對胰島素的靈敏度,，減少體重增加。這些結(jié)果表明,，SCD1對代謝綜合癥中生成其它成分的FH個體來說可能是一種潛在的藥物靶標(biāo),。
相關(guān)論文發(fā)表于2008年1月份的《油脂研究期刊》（Journal of Lipid Research，JLR）,。
生物谷推薦原始出處：
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: [email protected]
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
