Stearoyl CoA desaturase 1 is elevated in obesity but protects against fatty acid-induced skeletal muscle insulin resistance in vitro.
OBJECTIVE
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
SCD1 protects from cellular toxicity in L6 myotubes by preventing excessive accumulation of bioactive lipid metabolites.
Pinnamaneni
S K
SK
Cellular and Molecular Metabolism Laboratory, School of Medical Sciences, RMIT University, Melbourne, Victoria, Australia.
Southgate
R J
RJ
Febbraio
M A
MA
Watt
M J
MJ
D000818:Animals; D003847:Deoxyglucose / Q000378:metabolism; D005227:Fatty Acids / Q000502:physiology; D015971:Gene Expression Regulation, Enzymologic; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018485:Muscle Fibers, Skeletal / Q000201:enzymology; D018482:Muscle, Skeletal / Q000201:enzymology* / Q000503:physiopathology*; D009765:Obesity / Q000201:enzymology*; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics; D013230:Stearoyl-CoA Desaturase / Q000235:genetics* / Q000378:metabolism; D014162:Transfection
D005227:Fatty Acids; D034741:RNA, Small Interfering; D003847:Deoxyglucose; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase; D051057:Proto-Oncogene Proteins c-akt