Skeletal Muscle Lipid Composition Parallels Clinical Phenotype Extremes

Abstract

Intramyocellular lipid (IMCL) is generally associated with insulin resistance and lipotoxicity. However, the “athlete’s paradox” is well documented, where IMCL levels are similar between athletes and patients with type 2 diabetes despite discrepant levels of insulin sensitivity. Differences in muscle lipid metabolites between aerobically trained, lean, insulin-sensitive (LT) vs. sedentary, overweight/obese, insulin-resistant (OIR) individuals remain insufficiently characterized and may help to explain the “athlete’s paradox.” LT [n=14: 50% females, 28.5±1.6 years (Mean±SE)] and OIR [n=24: 79% females, 29.8±1.6 years] subjects each provided 2 muscle biopsies from the vastus lateralis (bilateral, 6 hours apart, ≥48 hours after last exercise, ≥8 fasting, overnight admission prior to biopsy) for mass spectrometry analysis. At a separate visit, insulin sensitivity was quantified by a hyperinsulinemic-euglycemic clamp (mg glucose/kg FFM/min). As the sequential biopsy results were not significantly different, the results were averaged for each subject. Compared with the OIR group, the LT group had lower BMI (22.3±0.5 vs. 36.2±1.2 kg/m2:p<0.01), higher fitness (VO2max:53.4±2.2 vs. 26.7±1.1 ml/kg/min: p<0.01), and higher insulin sensitivity (M-value: 17.1±0.7 vs. 8±0.5, p<0.01). Muscle triglycerides in the LT group were lower (nmol/mg muscle) in oleic acid (3.2±0.6 vs. 6.0±1.0, p=0.02) and palmitic acid (1.5±0.2 vs. 3.1±0.5, p<0.01) than the OIR group. Diacylglycerol (DAG) and palmitoylcarnitine concentrations were not significantly different. Only in the OIR group, palmitoylcarnitine correlated with the following: oleic acid (r=0.73, p<0.01), palmitic acid (r=0.73, p<0.01) and DAG (dipalmitate:r=0.53, p=0.03, palmitate+oleate: r=0.51, p=0.04). These findings suggest that either incomplete muscle lipid oxidation or increased acylcarnitine generation is present in the OIR group, thus warranting further research on training effects on muscle lipid turnover. Disclosure L.S. Chow: Research Support; Self; Eli Lilly and Company, National Institute of Diabetes and Digestive and Kidney Diseases. D.G. Mashek: None. T. Bosch: None. A. Bantle: None. M. Petterson: None. D.R. Dengel: None. M.D. Jensen: Other Relationship; Self; Novo Nordisk A/S. Consultant; Self; Novo Nordisk A/S.