Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro
Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro
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DOI：
10.1007/s00125-006-0427-9
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发表时间：
2006-12-01
期刊：
影响因子：
8.2
通讯作者：
Watt, M. J.
中科院分区：
文献类型：
--
作者：
Pinnamaneni, S. K.;Southgate, R. J.;Watt, M. J.
AIMS/假说硬脂酰辅酶A去饱和酶1(SCD1)与介导肥胖和胰岛素抵抗有关。矛盾的是，SCD1将饱和脂肪酸转化为单不饱和脂肪酸，饱和脂肪酸是一种与胰岛素抵抗有关的脂质物种。本研究旨在探讨SCD1在脂肪酸诱导的胰岛素抵抗发病机制中的作用机制。方法分别利用SCD1短干扰RNA(SiRNA)和脂质体介导的pcDNA3.1/hygro-mSCD1转基因技术，在大鼠L6骨骼肌管中瞬时减少或增加SCD1蛋白的表达。胰岛素刺激的Akt活性、磷酸化和2-脱氧葡萄糖摄取均被SCD1siRNA抑制。在对照组和SCD1siRNA肌管中，将L6肌管暴露于棕榈酸酯中均可消除胰岛素刺激的葡萄糖摄取。SCD1的过表达导致三酰甘油酯化，但减少神经酰胺和DAG的积累，并保护肌管免受脂肪酸诱导的胰岛素抵抗。结论/解释SCD1通过防止生物活性脂代谢产物的过度积累来保护L6肌管的细胞毒性。
Aims/hypothesis Stearoyl CoA desaturase 1 (SCD1) is implicated in mediating obesity and insulin resistance. Paradoxically, SCD1 converts saturated fatty acids, the lipid species implicated in mediating insulin resistance, to monounsaturated fatty acids. The aim of the present study was to assess the molecular mechanisms that implicate SCD1 in the aetiology of fatty acid-induced insulin resistance.Methods SCD1 protein was transiently decreased or increased in rat L6 skeletal muscle myotubes using SCD1 short interfering RNA (siRNA) or liposome-mediated transfection of pcDNA3.1/Hygro-mSCD1, respectively.Results Reducing SCD1 protein resulted in marked esterification of exogenous fatty acids into diacylglycerol (DAG) and ceramide. Insulin-stimulated Akt activity and phosphorylation and 2-deoxyglucose uptake were reduced with SCD1 siRNA. Exposure of L6 myotubes to palmitate abolished insulin-stimulated glucose uptake in both control and SCD1 siRNA myotubes. Overexpression of SCD1 resulted in triacylglycerol esterification but attenuated ceramide and DAG accumulation and protected myotubes from fatty acid-induced insulin resistance.Conclusions/interpretation SCD1 protects from cellular toxicity in L6 myotubes by preventing excessive accumulation of bioactive lipid metabolites.