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.
Keywords Ceramide - Diacylglycerol - Insulin resistance - Obesity - Palmitate - Skeletal muscle - Stearoyl CoA desaturase
An erratum to this article can be found online at http://dx.doi.org/10.1007/s00125-009-1566-6.