TY - JOUR
T1 - Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes
AU - Mezincescu, Alice M.
AU - Rudd, Amelia
AU - Cheyne, Lesley
AU - Horgan, Graham
AU - Philip, Sam
AU - Cameron, Donnie
AU - van Loon, Luc
AU - Whitfield, Phil
AU - Gribbin, Rachael
AU - Hu, May Khei
AU - Delibegovic, Mirela
AU - Fielding, Barbara
AU - Lobley, Gerald
AU - Thies, Frank
AU - Newby, David E.
AU - Gray, Stuart
AU - Henning, Anke
AU - Dawson, Dana
N1 - Funding Information:
The authors are grateful to Mr Simon Bath, Mr Baxter Millar and Mrs Christine Alexander, clinical trial pharmacists at Tayside Pharmaceuticals, Dundee, for the GMP-clinical grade preparation of the saturated and unsaturated fatty acids stable isotopes. Thanks go to Ms Amanda Cardy, Primary Care Research Network at the University of Aberdeen for the initial screening of primary care practices for identification of potential eligible candidates for the diabetes patient group. We thank Dr Nicola Jackson for assistance with the sample processing and measurements of isotopic enrichments at the Stable Isotope Mass Spectrometry Unit, University of Surrey. We offer our thanks and gratitude to Professor Bryan Bergman and Dr Leigh Perreault from the University of Colorado, USA, for their help and advice during the isotope sub-study. The MISTY study was funded by the British Heart Foundation Project Grant no. PG/15/88/31780, Muscle fat compartments and turnover as a determinant of insulin sensitivity, chief investigator D Dawson.
Publisher Copyright:
© The Author(s) 2024.
PY - 2024/12/1
Y1 - 2024/12/1
N2 - Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called “athlete’s paradox”. In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY).
AB - Despite opposing insulin sensitivity and cardiometabolic risk, both athletes and patients with type 2 diabetes have increased skeletal myocyte fat storage: the so-called “athlete’s paradox”. In a parallel non-randomised, non-blinded trial (NCT03065140), we characterised and compared the skeletal myocyte lipid signature of 29 male endurance athletes and 30 patients with diabetes after undergoing deconditioning or endurance training respectively. The primary outcomes were to assess intramyocellular lipid storage of the vastus lateralis in both cohorts and the secondary outcomes were to examine saturated and unsaturated intramyocellular lipid pool turnover. We show that athletes have higher intramyocellular fat saturation with very high palmitate kinetics, which is attenuated by deconditioning. In contrast, type 2 diabetes patients have higher unsaturated intramyocellular fat and blunted palmitate and linoleate kinetics but after endurance training, all were realigned with those of deconditioned athletes. Improved basal insulin sensitivity was further associated with better serum cholesterol/triglycerides, glycaemic control, physical performance, enhanced post insulin receptor pathway signalling and metabolic sensing. We conclude that insulin-resistant, maladapted intramyocellular lipid storage and turnover in patients with type 2 diabetes show reversibility after endurance training through increased contributions of the saturated intramyocellular fatty acid pools. Clinical Trial Registration: NCT03065140: Muscle Fat Compartments and Turnover as Determinant of Insulin Sensitivity (MISTY).
U2 - 10.1038/s41467-024-47843-y
DO - 10.1038/s41467-024-47843-y
M3 - Article
SN - 2041-1723
VL - 15
JO - Nature Communications
JF - Nature Communications
IS - 1
M1 - 3690
ER -