title: Insulin-stimulated glucose uptake and pathways regulating energy metabolism in skeletal muscle cells: the effects of subcutaneous and visceral fat, and long-chain saturated, n-3 and n-6 polyunsaturated fatty acids.
abstract: OBJECTIVE
  The study aims to determine the effect of long-chain saturated and polyunsaturated (PUFA) fatty acids, specifically palmitic acid (PA; 16:0), docosahexaenoic acid (DHA; 22:6n-3) and linoleic acid (LA; 18:2n-6), and their interactions with factors from adipose tissue, on insulin sensitivity and lipid metabolism in skeletal muscle.
  
  
  METHODS
  L6 myotubes were cultured with PA, DHA or LA (0.4mmol/l), with or without conditioned media from human subcutaneous (SC) and visceral (IAB) fat. Insulin-stimulated glucose uptake, lipid content, mRNA expression of key genes involved in nutrient utilization and protein expression of inhibitor protein inhibitor kappa B (IκB)-α and mammalian target of rapamycin (mTOR) were measured.
  
  
  RESULTS
  PA and IAB fat reduced insulin-stimulated glucose uptake and their combined effect was similar to that of PA alone. PA-induced insulin resistance was ameliorated by inhibiting the de novo synthesis of ceramide, IκBα degradation or mTOR activation. The PA effect was also partially reversed by DHA and completely by LA in the presence of SC fat. PA increased diacylglycerol content, which was reduced by LA and to a greater extent when either IAB or SC fat was also present. PA increased SCD1 whereas DHA and LA increased AMPKα2 mRNA. In the presence of SC or IAB fat, the combination of PA with either DHA or LA decreased SCD1 and increased AMPKα2 mRNA.
  
  
  CONCLUSIONS
  PA-induced insulin resistance in skeletal muscle involves inflammatory (nuclear factor kappa B/mTOR) and nutrient (ceramide) pathways. PUFAs promote pathways, at a transcriptional level, that increase fat oxidation and synergize with factors from SC fat to abrogate PA-induced insulin resistance.
authors.affiliation: Boden Institute of Obesity, Nutrition, Exercise and Eating Disorders, University of Sydney, Sydney NSW 2006, Australia. yan.lam@sydney.edu.au
authors.forename: Y Y
authors.initials: YY
authors.lastname: Lam
authors.forename: G
authors.initials: G
authors.lastname: Hatzinikolas
authors.forename: J M
authors.initials: JM
authors.lastname: Weir
authors.forename: A
authors.initials: A
authors.lastname: Janovská
authors.forename: A J
authors.initials: AJ
authors.lastname: McAinch
authors.forename: P
authors.initials: P
authors.lastname: Game
authors.forename: P J
authors.initials: PJ
authors.lastname: Meikle
authors.forename: G A
authors.initials: GA
authors.lastname: Wittert
mesh_terms: D000818:Animals; D001693:Biological Transport, Active / Q000187:drug effects; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism; D017077:Culture Media, Conditioned; D004281:Docosahexaenoic Acids / Q000494:pharmacology; D004734:Energy Metabolism / Q000187:drug effects; D005227:Fatty Acids / Q000494:pharmacology*; D015870:Gene Expression / Q000187:drug effects; D005947:Glucose / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000378:metabolism; D019787:Linoleic Acid / Q000494:pharmacology; D018485:Muscle Fibers, Skeletal / Q000187:drug effects* / Q000378:metabolism*; D016328:NF-kappa B / Q000378:metabolism; D019308:Palmitic Acid / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction / Q000187:drug effects; D050151:Subcutaneous Fat / Q000378:metabolism; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism
chemical_list: D002518:Ceramides; D017077:Culture Media, Conditioned; D005227:Fatty Acids; D007328:Insulin; D016328:NF-kappa B; D012333:RNA, Messenger; D004281:Docosahexaenoic Acids; D019308:Palmitic Acid; D019787:Linoleic Acid; D058570:TOR Serine-Threonine Kinases; D005947:Glucose