Exercise Training Counteracts Compromised Mitochondrial Capacity Induced by Energy Restriction in Prediabetics in a Sex‐Dependent Manner

The objective of this randomized controlled trial was to examine if exercise training can counteract energy restriction-induced impairment of mitochondrial capacity in skeletal muscle of 55-70-years people with prediabetes and metabolic syndrome. The potential impact of sex was explored. Fifty sedentary men and women with prediabetes and metabolic syndrome (age: 61 ± 6 (±SD) years, BMI: 29.6 ± 4.7 kg·m^-2, body fat content: 37.5% ± 8.2% and VO_2max: 22.3 ± 5.7 mL·min^-1·kg^-1) were randomized to either exercise training and dietary advice (EX-DI) or dietary advice only (DI). Dietary advice aimed to induce weight loss and improve glycemic control. Exercise consisted of 32 ± 2 mixed 30-60 min training sessions with recreational small-sided soccer distributed across 16 weeks. Maximal activity and protein abundance of key regulatory mitochondrial enzymes were determined in m. vastus lateralis pre- and post-intervention. Muscle glycogen content was also determined. Dietary advice only (DI), impaired (p < 0.001) citrate synthase (CS), and 3-hydroxyacyl-CoA dehydrogenase (HAD) maximal activity by 18% ± 43% and 23% ± 19%, respectively. When combined with exercise training, no dietary impairment of CS or HAD maximal activity was detectable. Superoxide dismutase 2 (SOD2) and CS protein expression also declined (p < 0.05) in DI and remained unchanged in EX-DI. In terms of sex differences, a decrease in maximal CS activity in both EX-DI and DI was observed exclusively in men (all p < 0.05). In conclusion, 16 weeks of exercise training counteracts energy restriction-induced impairment in skeletal mitochondrial function in 55- to 70-year-old women and men with prediabetes and metabolic syndrome.