Pinnamaneni S K, Southgate R J, Febbraio M A, Watt M J
Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, RMIT University, Melbourne, Victoria, Australia.
Diabetologia. 2006 Dec;49(12):3027-37. doi: 10.1007/s00125-006-0427-9. Epub 2006 Oct 11.
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.
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.
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.
目的/假设：硬脂酰辅酶A去饱和酶1（SCD1）与肥胖和胰岛素抵抗的发生有关。矛盾的是，SCD1可将与胰岛素抵抗相关的饱和脂肪酸转化为单不饱和脂肪酸。本研究旨在评估SCD1在脂肪酸诱导的胰岛素抵抗病因学中发挥作用的分子机制。
分别使用SCD1小干扰RNA（siRNA）或脂质体介导的pcDNA3.1/Hygro-mSCD1转染，使大鼠L6骨骼肌肌管中的SCD1蛋白短暂减少或增加。
SCD1蛋白减少导致外源性脂肪酸显著酯化生成二酰甘油（DAG）和神经酰胺。SCD1 siRNA降低了胰岛素刺激的Akt活性、磷酸化水平以及2-脱氧葡萄糖摄取。L6肌管暴露于棕榈酸酯后，对照和SCD1 siRNA肌管中胰岛素刺激的葡萄糖摄取均被消除。SCD1过表达导致三酰甘油酯化，但减弱了神经酰胺和DAG的积累，并保护肌管免受脂肪酸诱导的胰岛素抵抗。
结论/解读：SCD1通过防止生物活性脂质代谢产物的过度积累，保护L6肌管免受细胞毒性。
