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

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dc.contributor.authorLam, Y.
dc.contributor.authorHatzinikolas, G.
dc.contributor.authorWeir, J.
dc.contributor.authorJanovska, A.
dc.contributor.authorMcAinch, A.
dc.contributor.authorGame, P.
dc.contributor.authorMeikle, P.
dc.contributor.authorWittert, G.
dc.date.issued2011
dc.description.abstract<h4>Aims</h4>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.<h4>Methods</h4>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.<h4>Results</h4>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.<h4>Conclusions</h4>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.
dc.description.statementofresponsibilityY.Y. Lam, G. Hatzinikolas, J.M. Weir, A. Janovská, A.J. McAinch, P. Game, P.J. Meikle, G.A. Wittert
dc.identifier.citationBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids, 2011; 1811(7-8):468-475
dc.identifier.doi10.1016/j.bbalip.2011.04.011
dc.identifier.issn1388-1981
dc.identifier.issn1879-2618
dc.identifier.orcidHatzinikolas, G. [0000-0001-5430-6396]
dc.identifier.orcidWittert, G. [0000-0001-6818-6065]
dc.identifier.urihttp://hdl.handle.net/2440/70487
dc.language.isoen
dc.publisherElsevier Science BV
dc.rightsCopyright © 2011 Elsevier B.V. All rights reserved.
dc.source.urihttps://doi.org/10.1016/j.bbalip.2011.04.011
dc.subjectInsulin resistance
dc.subjectLipid metabolism
dc.subjectAdipokine
dc.titleInsulin-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
dc.typeJournal article
pubs.publication-statusPublished

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