Lipid partitioning, incomplete fatty acid oxidation, and insulin signal transduction in primary human muscle cells: effects of severe obesity, fatty acid incubation, and fatty acid translocase/CD36 overexpression.
BACKGROUND
Intracellular lipid partitioning toward storage and the incomplete oxidation of fatty acids (FA) have been linked to insulin resistance.


OBJECTIVE
To gain insight into how intracellular lipid metabolism is related to insulin signal transduction, we examined the effects of severe obesity, excess FA, and overexpression of the FA transporter, FA translocase (FAT)/CD36, in primary human skeletal myocytes.


METHODS
Insulin signal transduction, FA oxidation, and metabolism were measured in skeletal muscle cells harvested from lean and severely obese women. To emulate the obesity phenotype in our cell culture system, we incubated cells from lean individuals with excess FA or overexpressed FAT/CD36 using recombinant adenoviral technology.


RESULTS
Complete oxidation of FA was significantly reduced, whereas total lipid accumulation, FA esterification into lipid intermediates, and incomplete oxidation were up-regulated in the muscle cells of severely obese subjects. Insulin signal transduction was reduced in the muscle cells from severely obese subjects compared to lean controls. Incubation of muscle cells from lean subjects with lipids reduced insulin signal transduction and increased lipid storage and incomplete FA oxidation. CD36 overexpression increased FA transport capacity, but did not impair complete FA oxidation and insulin signal transduction in muscle cells from lean subjects.


CONCLUSIONS
Cultured myocytes from severely obese women express perturbations in FA metabolism and insulin signaling reminiscent of those observed in vivo. The obesity phenotype can be recapitulated in muscle cells from lean subjects via exposure to excess lipid, but not by overexpressing the FAT/CD36 FA transporter.
Bell
Jill A
JA
East Carolina University, Brody Medical School, Department of Physiology, 600 Moye Boulevard, Greenville, NC 27834, USA.
Reed
Melissa A
MA
Consitt
Leslie A
LA
Martin
Ola J
OJ
Haynie
Kimberly R
KR
Hulver
Matthew W
MW
Muoio
Deborah M
DM
Dohm
G Lynis
GL
D000328:Adult; D000704:Analysis of Variance; D015153:Blotting, Western; D018955:CD36 Antigens / Q000235:genetics / Q000378:metabolism; D002478:Cells, Cultured; D050612:Fatty Acid Transport Proteins / Q000235:genetics / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D018485:Muscle Fibers, Skeletal / Q000378:metabolism*; D009767:Obesity, Morbid / Q000235:genetics / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology
D018955:CD36 Antigens; D050612:Fatty Acid Transport Proteins; D005227:Fatty Acids; D007328:Insulin