Comparison of intramyocellular lipid metabolism in patients with diabetes and male athletes

Alice M. Mezincescu, Amelia Rudd, Lesley Cheyne, Graham Horgan, Sam Philip, Donnie Cameron, Luc Loon, Phil Whitfield, Rachael Gribbin, May Khei Hu, Mirela Delibegovic, Barbara Fielding, Gerald Lobley, Frank Thies, David E. Newby, Stuart Gray, Anke Henning and Dana Dawson ()
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Alice M. Mezincescu: University of Aberdeen
Amelia Rudd: University of Aberdeen
Lesley Cheyne: University of Aberdeen
Graham Horgan: Biomathematics & Statistics Scotland
Sam Philip: University of Aberdeen
Donnie Cameron: Leiden University Medical Center
Luc Loon: University of Maastricht
Phil Whitfield: University of Glasgow
Rachael Gribbin: University of Surrey
May Khei Hu: University of Aberdeen
Mirela Delibegovic: University of Aberdeen
Barbara Fielding: University of Surrey
Gerald Lobley: University of Aberdeen
Frank Thies: University of Aberdeen
David E. Newby: University of Edinburgh
Stuart Gray: University of Glasgow
Anke Henning: Southwestern University
Dana Dawson: University of Aberdeen

Nature Communications, 2024, vol. 15, issue 1, 1-14

Abstract: Abstract 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)

Date: 2024
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DOI: 10.1038/s41467-024-47843-y

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