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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

Lam, Yan and Hatzinikolas, George and Weir, J and Janovska, Alena and McAinch, Andrew and Game, Philip and Meikle, P and Wittert, Gary (2011) 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. Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids, 1811 (7-8). pp. 468-475. ISSN 1388-1981

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Abstract

Aims. 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 (0.4 mmol/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.

Item Type: Article
Uncontrolled Keywords: ResPubID22866, insulin resistance, lipid metabolism, adipokine
Subjects: Faculty/School/Research Centre/Department > School of Biomedical and Health Sciences
FOR Classification > 1116 Medical Physiology
SEO Classification > 9201 Clinical Health (Organs, Diseases and Abnormal Conditions)
Depositing User: VUIR
Date Deposited: 27 Jun 2012 02:22
Last Modified: 05 Jun 2013 23:44
URI: http://vuir.vu.edu.au/id/eprint/7640
DOI: 10.1016/j.bbalip.2011.04.011
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Citations in Scopus: 19 - View on Scopus

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