Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans

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Tonks, KT; Coster, ACF; Christopher, MJ; Chaudhuri, R; Xu, A; Gagnon-Bartsch, J; Chisholm, DJ; James, DE; Meikle, PJ; Greenfield, JR; ...Date
2016-04-01Source Title
ObesityPublisher
WILEYUniversity of Melbourne Author/s
Meikle, PeterAffiliation
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Tonks, K. T., Coster, A. C. F., Christopher, M. J., Chaudhuri, R., Xu, A., Gagnon-Bartsch, J., Chisholm, D. J., James, D. E., Meikle, P. J., Greenfield, J. R. & Samocha-Bonet, D. (2016). Skeletal muscle and plasma lipidomic signatures of insulin resistance and overweight/obesity in humans. OBESITY, 24 (4), pp.908-916. https://doi.org/10.1002/oby.21448.Access Status
Open AccessAbstract
OBJECTIVE: Alterations in lipids in muscle and plasma have been documented in insulin-resistant people with obesity. Whether these lipid alterations are a reflection of insulin resistance or obesity remains unclear. METHODS: Nondiabetic sedentary individuals not treated with lipid-lowering medications were studied (n = 51). Subjects with body mass index (BMI) > 25 kg/m(2) (n = 28) were stratified based on median glucose infusion rate during a hyperinsulinemic-euglycemic clamp into insulin-sensitive and insulin-resistant groups (above and below median, obesity/insulin-sensitive and obesity/insulin-resistant, respectively). Lean individuals (n = 23) served as a reference group. Lipidomics was performed in muscle and plasma by liquid chromatography electrospray ionization-tandem mass spectrometry. Pathway analysis of gene array in muscle was performed in a subset (n = 35). RESULTS: In muscle, insulin resistance was characterized by higher levels of C18:0 sphingolipids, while in plasma, higher levels of diacylglycerol and cholesterol ester, and lower levels of lysophosphatidylcholine and lysoalkylphosphatidylcholine, indicated insulin resistance, irrespective of overweight/obesity. The sphingolipid metabolism gene pathway was upregulated in muscle in insulin resistance independent of obesity. An overweight/obesity lipidomic signature was only apparent in plasma, predominated by higher triacylglycerol and lower plasmalogen species. CONCLUSIONS: Muscle C18:0 sphingolipids may play a role in insulin resistance independent of excess adiposity.
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