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Abstract

Background:
High levels of tri- and di-acylglycerols are found in skeletal muscle of endurance trained athletic healthy volunteers (Athl-HV) and type 2 diabetes patients (T2D), however their metabolic phenotypes are at opposite ends of insulin sensitivity and cardiometabolic risk. Here we investigated if intramyocellular lipid saturation may constitute a previously unknown determinant of cardiometabolic risk. Secondly, we explored if deconditioning/exercise training impacts on intramyocellular lipid saturation in Athl-HV/T2D, respectively.
Methods:
Age matched male Athl-HV and T2D were enrolled. Athl-HV performed endurance training ≥5 years, actively training ≥360 minutes/week; T2D performed ≤150 min exercise/week. Bike-cardiopulmonary exercise testing (CPET), blood sampling for insulin sensitivity (HOMA2-IR*) and single voxel 1H-magnetic resonance spectroscopy (1H-MRS) of the right vastus lateralis were performed in all at baseline and after exercise intervention (4 week deconditioning in Athl-HV and investigator-supervised bike training at ≥65% of baseline peakVO2, 5 hours/week x 8 weeks in T2D). 1H-MRS was acquired on 3T Philips Achieva with a 16-channel coil, point-resolved spectroscopy, variable pulse power and optimized relaxation delay water suppression.
1H-MRS data were analysed in LCModel. Intensities of total, saturated and unsaturated intra- and extra-myocellular lipids and creatine resonance lines were normalized to internal water. Fractional lipid mass (fLM) [lipid/(lipid+water)] as well as fractions of saturated (fSL) (saturated/total) and unsaturated (fUL) (unsaturated/total) lipid components were calculated. Data were analysed by paired/unpaired t tests and shown as mean±SEM. Significance was set at p<0.05.
Results:
Deconditioning/exercise traning led to significant weight gain/loss in Athl-HV/T2D, respectively. Peak VO2 significantly decreased in Athl-HV and increased in T2D. Insulin sensitivity was higher in Athl-HV than T2D (Table 1).
Higher fLM was found in the skeletal muscle of T2D compared to Athl-HV, at baseline (p=0.002) and after exercise intervention (p=0.03), Figure 1A.
At baseline, T2D had a trend for lower fSL and higher fUL compared to Athl-HV (80±8 vs 86±1% and 19±3 vs 14±7%, p=0.07 for both). Neither fSL nor fUL changed with deconditioning in Athl-HV. However, exercise training resulted in a significant increase in fSL (80±8 to 88±3%) and reciprocal decrease in fUL (19±9 to 12±3%) in T2D (both p=0.004), Figure 1B and C.
Conclusion:
We demonstrate differences in total amount and saturation of intramyocellular lipids between Athl-HV and T2D. Further, intramyocellular lipid saturation is modulated by exercise training in T2D, to mirror the phenotype seen in Athl-HV, implying that this may be either an independent or an earlier marker of improved cardio-metabolic health than insulin sensitivity.