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Sexual dimorphism of substrate utilization: Differences in skeletal muscle mitochondrial volume density and function

Journal article
Authors D. Montero
Klavs Madsen
A. K. Meinild-Lundby
Fredrik Edin
Carsten Lundby
Published in Experimental Physiology
Volume 103
Issue 6
Pages 851-859
ISSN 0958-0670
Publication year 2018
Published at Department of Food and Nutrition, and Sport Science
Pages 851-859
Language en
Keywords body size, fat oxidation, mitochondria, sex differences, substrate metabolism, endurance exercise, gender-differences, fat oxidation, submaximal, exercise, enzyme-activity, oxygen-uptake, body-mass, women, men, metabolism, Physiology
Subject categories Physiology


Fat oxidation during exercise is greater in females than in males. We sought to determine whether sex differences in substrate metabolism are paralleled by distinct skeletal muscle mitochondrial volume density and oxidative capacity. Whole-body substrate (fat and carbohydrate) utilization during submaximal treadmill running was assessed, and skeletal muscle biopsies were taken to determine mitochondrial volume density and function in healthy young females (n=12) and males (n=12) matched by aerobic exercise capacity and exercise performance. Females presented a lower respiratory exchange ratio (0.87 +/- 0.04 versus 0.91 +/- 0.04, P=0.023) and whole-body carbohydrate oxidation (27.8 +/- 8.3 versus 35.8 +/- 6.5mgkg(-1)min(-1), P=0.027), whereas fat oxidation was higher (8.7 +/- 2.8 versus 5.9 +/- 2.6mgkg(-1)min(-1), P=0.034) during submaximal exercise compared with males. In skeletal muscle biopsies, females demonstrated augmented mitochondrial volume density (7.51 +/- 1.77 versus 5.90 +/- 1.72%, P=0.035) and oxidative capacity for fatty acid [36.6 +/- 12.8 versus 24.5 +/- 7.3pmol O(2)s(-1)(mg wet weight)(-1), P=0.009] and lactate [71.1 +/- 24.4 versus 53.2 +/- 14.6pmol O(2)s(-1)(mg wet weight)(-1), P=0.040]. No sex differences in respiratory exchange ratio, whole-body fat oxidation and skeletal muscle variables were detected when adjusted for anthropometric variables including body mass or leg mass, which were lower in females. In conclusion, female prioritization of fat over carbohydrate oxidation during exercise is underpinned by augmented body size-related mitochondrial volume density, fatty acid and lactate oxidative capacity in skeletal muscle fibres.

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