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Saturated and Unsaturated Intramyocellular Lipid Profiles and their Dynamic Changes after Exercise Intervention in Athletic Healthy Volunteers and Type 2 Diabetes Patients: an in vivo 1H-MRS study
{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 $\geq$5 years, actively training $\geq$360 minutes/week; T2D performed $\leq$150 min exercise/week. Bike-cardiopulmonary exercise testing (CPET), blood sampling for insulin sensitivity (HOMA2-IR\textasteriskcentered) 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 $\geq$65\textpercent of baseline peakVO2, 5 hours/week x 8 weeks in T2D). 1H-MRS was acquired on 3T Philips Achieva with a 16-channel coil, point-resolved spectroscopy, variable pulse power and optimized relaxation delay water suppression. 1H-MRS data were analysed in LCModel. Intensities of total, saturated and unsaturated intra- and extra-myocellular lipids and creatine resonance lines were normalized to internal water. Fractional lipid mass (fLM) [lipid/(lipid+water)] as well as fractions of saturated (fSL) (saturated/total) and unsaturated (fUL) (unsaturated/total) lipid components were calculated. Data were analysed by paired/unpaired t tests and shown as mean$\pm$SEM. Significance was set at p\textless0.05. Results: Deconditioning/exercise traning led to significant weight gain/loss in Athl-HV/T2D, respectively. Peak VO2 significantly decreased in Athl-HV and increased in T2D. Insulin sensitivity was higher in Athl-HV than T2D (Table 1). Higher fLM was found in the skeletal muscle of T2D compared to Athl-HV, at baseline (p\textequals0.002) and after exercise intervention (p\textequals0.03), Figure 1A. At baseline, T2D had a trend for lower fSL and higher fUL compared to Athl-HV (80$\pm$8 vs 86$\pm$1\textpercent and 19$\pm$3 vs 14$\pm$7\textpercent, p\textequals0.07 for both). Neither fSL nor fUL changed with deconditioning in Athl-HV. However, exercise training resulted in a significant increase in fSL (80$\pm$8 to 88$\pm$3\textpercent) and reciprocal decrease in fUL (19$\pm$9 to 12$\pm$3\textpercent) in T2D (both p\textequals0.004), 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.}
@misc{item_3034570, title = {{Saturated and Unsaturated Intramyocellular Lipid Profiles and their Dynamic Changes after Exercise Intervention in Athletic Healthy Volunteers and Type 2 Diabetes Patients: an in vivo 1H-MRS study}}, booktitle = {{SCMR 22nd Annual Scientific Sessions: Global CMR: Innovation and Clinical Outcomes}}, 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 $\geq$5 years, actively training $\geq$360 minutes/week; T2D performed $\leq$150 min exercise/week. Bike-cardiopulmonary exercise testing (CPET), blood sampling for insulin sensitivity (HOMA2-IR\textasteriskcentered) 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 $\geq$65\textpercent of baseline peakVO2, 5 hours/week x 8 weeks in T2D). 1H-MRS was acquired on 3T Philips Achieva with a 16-channel coil, point-resolved spectroscopy, variable pulse power and optimized relaxation delay water suppression. 1H-MRS data were analysed in LCModel. Intensities of total, saturated and unsaturated intra- and extra-myocellular lipids and creatine resonance lines were normalized to internal water. Fractional lipid mass (fLM) [lipid/(lipid+water)] as well as fractions of saturated (fSL) (saturated/total) and unsaturated (fUL) (unsaturated/total) lipid components were calculated. Data were analysed by paired/unpaired t tests and shown as mean$\pm$SEM. Significance was set at p\textless0.05. Results: Deconditioning/exercise traning led to significant weight gain/loss in Athl-HV/T2D, respectively. Peak VO2 significantly decreased in Athl-HV and increased in T2D. Insulin sensitivity was higher in Athl-HV than T2D (Table 1). Higher fLM was found in the skeletal muscle of T2D compared to Athl-HV, at baseline (p\textequals0.002) and after exercise intervention (p\textequals0.03), Figure 1A. At baseline, T2D had a trend for lower fSL and higher fUL compared to Athl-HV (80$\pm$8 vs 86$\pm$1\textpercent and 19$\pm$3 vs 14$\pm$7\textpercent, p\textequals0.07 for both). Neither fSL nor fUL changed with deconditioning in Athl-HV. However, exercise training resulted in a significant increase in fSL (80$\pm$8 to 88$\pm$3\textpercent) and reciprocal decrease in fUL (19$\pm$9 to 12$\pm$3\textpercent) in T2D (both p\textequals0.004), 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.}}, year = {2019}, slug = {item_3034570}, author = {Mezinescu, A and Ahearn, T and Rudd, A and Scally, C and Cheynne, L and Abbas, H and Horgan, G and Philip, S and Delibegovic, M and Lobley, G and Thies, F and Gray, S and Henning, A and Dawson, D} }