Elevated stearoyl-CoA desaturase-1 expression in skeletal muscle contributes to abnormal fatty acid partitioning in obese humans.
Obesity and type 2 diabetes are strongly associated with abnormal lipid metabolism and accumulation of intramyocellular triacylglycerol, but the underlying cause of these perturbations are yet unknown. Herein, we show that the lipogenic gene, stearoyl-CoA desaturase 1 (SCD1), is robustly up-regulated in skeletal muscle from extremely obese humans. High expression and activity of SCD1, an enzyme that catalyzes the synthesis of monounsaturated fatty acids, corresponded with low rates of fatty acid oxidation, increased triacylglycerol synthesis and increased monounsaturation of muscle lipids. Elevated SCD1 expression and abnormal lipid partitioning were retained in primary skeletal myocytes derived from obese compared to lean donors, implying that these traits might be driven by epigenetic and/or heritable mechanisms. Overexpression of human SCD1 in myotubes from lean subjects was sufficient to mimic the obese phenotype. These results suggest that elevated expression of SCD1 in skeletal muscle contributes to abnormal lipid metabolism and progression of obesity.
Hulver
Matthew W
MW
Pennington Biomedical Research, Louisiana State University System, Baton Rouge, Louisiana 70808, USA. hulvermw@pbrc.edu
Berggren
Jason R
JR
Carper
Michael J
MJ
Miyazaki
Makoto
M
Ntambi
James M
JM
Hoffman
Eric P
EP
Thyfault
John P
JP
Stevens
Robert
R
Dohm
G Lynis
GL
Houmard
Joseph A
JA
Muoio
Deborah M
DM
D015992:Body Mass Index; D016022:Case-Control Studies; D002478:Cells, Cultured; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D066298:In Vitro Techniques; D050356:Lipid Metabolism; D046228:Microarray Analysis; D018485:Muscle Fibers, Skeletal / Q000166:cytology / Q000378:metabolism; D018482:Muscle, Skeletal / Q000166:cytology / Q000201:enzymology* / Q000378:metabolism; D009765:Obesity / Q000378:metabolism*; D013230:Stearoyl-CoA Desaturase / Q000235:genetics / Q000378:metabolism*; D013851:Thinness; D014162:Transfection
D005227:Fatty Acids; D013230:Stearoyl-CoA Desaturase