Fatty acid-induced defects in insulin signalling, in myotubes derived from children, are related to ceramide production from palmitate rather than the accumulation of intramyocellular lipid

• Published in: Journal of cellular physiology 2007-04, Vol.211 (1), p.244-252
• Main Authors: Sabin, Matthew A., Stewart, Claire E.H., Crowne, Elizabeth C., Turner, Stephen J., Hunt, Linda P., Welsh, Gavin I., Grohmann, Malcolm J., Holly, Jeff M.P., Shield, Julian P.H.
• Format: Article
• Language: English
• Subjects: Cell Differentiation - drug effects; Cells, Cultured; Ceramides - biosynthesis; Child; Child, Preschool; Dose-Response Relationship, Drug; Female; Humans; Infant; Insulin - metabolism; Insulin - pharmacology; Lipid Metabolism - drug effects; Male; Muscle Fibers, Skeletal - drug effects; Muscle Fibers, Skeletal - metabolism; Oleic Acid - pharmacology; Oxazines; Palmitates - metabolism; Palmitates - pharmacology; Phosphoproteins - metabolism; Phosphoserine - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Signal Transduction - drug effects; Time Factors
• ISSN: 0021-9541; 1097-4652
• DOI: 10.1002/jcp.20922

The elevation of free fatty acids (FFAs), observed in childhood obesity results in intramyocellular lipid (IMCL) accumulation with consequent insulin resistance. Using in vitro differentiated myotubes from normal weight pre‐pubertal children (n = 8), we examined the effects of saturated (palmitate) and unsaturated (oleate) FFAs on insulin‐stimulated AKT phosphorylation (pAKT) and IMCL accumulation. Palmitate decreased pAKT (Mean [SEM] % change pAKT with palmitate 750 µM vs. control; pThr308 site −50.5% [28.7] and pSer473 site −38.7% [11.7]; P