Sexual dimorphism of substrate utilization: Differences in skeletal muscle mitochondrial volume density and function
Abstract
New Findings: What is the central question of this study? Females rely to a greater extent than males on fat oxidation during exercise. Whether any difference in skeletal muscle mitochondrial phenotype and oxidative capacity contributes to this sexual dimorphism remains incompletely explored. What is the main finding and its importance? Female prioritization of fat during exercise occurs in parallel to augmented mitochondrial volume density and intrinsic fatty acid and lactate oxidation in skeletal muscle fibres compared with males, independently of aerobic exercise capacity. The enlarged metabolic machinery in skeletal muscle of females is associated with lower body size and leg mass. 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 ± 6.5 mg kg−1 min−1, P = 0.027), whereas fat oxidation was higher (8.7 ± 2.8 versus 5.9 ± 2.6 mg kg−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 ± 7.3 pmol O 2 s−1 (mg wet weight)−1, P = 0.009] and lactate [71.1 ± 24.4 versus 53.2 ± 14.6 pmol 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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Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent.
“Significant sex differences and sex hormone influences on carbohydrate and lipid metabolism are apparent”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [17]
Important sex differences exist in mitochondrial function, substrate utilization, insulin sensitivity, immune responses, muscle morphology and body composition, iron metabolism, thermoregulation, hydration, appetite control, and energy availability and endocrine function.
“important sex differences exist in mitochondrial function [14–16], substrate utilization, and insulin sensitivity [17–24], immune responses [25–28], muscle morphology and body composition [29–32], iron metabolism [33–40], thermoregulation [41–44], hydration [45,46]{Sims, 2008 #55, [47–53], appetite control [54–59], and energy availability and endocrine function [60–65].”
From International society of sports nutrition position stand: nutritional concerns of the female athlete (2023) · cites this paper as [17]
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- Authors
- Montero, D., Madsen, K., Meinild‐Lundby, A., Edin, F., & Lundby, C.
- Affiliations
- University of Zurich (CH)
- University of Gothenburg (SE)
- Corresponding author
- Lundby, Carsten
- Venue
- Experimental Physiology
- Publisher
- Wiley
- Published
- 2018-05-08
- Volume
- 103
- Issue
- 6
- Pages
- 851-859
- ISSN
- 0958-0670 (ISSN-L)
- 1469-445X
- OpenAlex
- W2795887874
- Cited by
- 105
- References
- 52
- Citations by year
- 2026: 7 · 2025: 13 · 2024: 12 · 2023: 16 · 2022: 22 · 2021: 12 · 2020: 10 · 2019: 8 · 2018: 5
- FWCI
- 12.01
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Experimental Physiology (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Centrum for Idrottsforskning (P2014‐0030)
- Topics
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Keywords
- sexual dimorphism, substrate utilization, fat oxidation, skeletal muscle mitochondria, mitochondrial volume density, oxidative capacity, fatty acid oxidation, lactate oxidation, respiratory exchange ratio, carbohydrate oxidation, aerobic exercise capacity, leg mass, body size, mitochondrial biogenesis, mitochondrial fission and fusion, mitochondrial quality control
- MeSH terms
- Adult, Body Composition, Exercise Test, Fatty Acids, Female, Humans, Male, Mitochondria, Muscle, Oxidation-Reduction, Sex Characteristics, Exercise, Exercise Tolerance, Muscle Fibers, Skeletal, Lipid Metabolism, Mitochondrial Size
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