Human Skeletal Muscle Mitochondrial Uncoupling Is Associated with Cold Induced Adaptive Thermogenesis
Open accessAbstract
BACKGROUND: Mild cold exposure and overfeeding are known to elevate energy expenditure in mammals, including humans. This process is called adaptive thermogenesis. In small animals, adaptive thermogenesis is mainly caused by mitochondrial uncoupling in brown adipose tissue and regulated via the sympathetic nervous system. In humans, skeletal muscle is a candidate tissue, known to account for a large part of the epinephrine-induced increase in energy expenditure. However, mitochondrial uncoupling in skeletal muscle has not extensively been studied in relation to adaptive thermogenesis in humans. Therefore we hypothesized that cold-induced adaptive thermogenesis in humans is accompanied by an increase in mitochondrial uncoupling in skeletal muscle. METHODOLOGY/PRINCIPAL FINDINGS: The metabolic response to mild cold exposure in 11 lean, male subjects was measured in a respiration chamber at baseline and mild cold exposure. Skeletal muscle mitochondrial uncoupling (state 4) was measured in muscle biopsies taken at the end of the respiration chamber stays. Mild cold exposure caused a significant increase in 24h energy expenditure of 2.8% (0.32 MJ/day, range of -0.21 to 1.66 MJ/day, p<0.05). The individual increases in energy expenditure correlated to state 4 respiration (p<0.02, R(2) = 0.50). CONCLUSIONS/SIGNIFICANCE: This study for the first time shows that in humans, skeletal muscle has the intrinsic capacity for cold induced adaptive thermogenesis via mitochondrial uncoupling under physiological conditions. This opens possibilities for mitochondrial uncoupling as an alternative therapeutic target in the treatment of obesity.
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Indirect evidence from malignant hyperthermia and mild cold exposure in humans suggest that muscle NST mechanisms may exist.
“Clearly, indirect evidence from malignant hyperthermia 44 and mild cold exposure in humans 45 suggest that such mechanisms may exist and that further investigation of this area is warranted.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [45]
Mild cold exposure at 16 °C induces muscle mitochondrial uncoupling and increases energy expenditure via NST.
“Mild cold exposure (16 °C) also induces muscle mitochondrial uncoupling and increases energy expenditure via NST 45.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [45]
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- Authors
- Wijers, S. L. J., Schrauwen, P., Saris, W. H. M., & van Marken Lichtenbelt, W. D.
- Affiliations
- Maastricht University (NL)
- Corresponding author
- Wijers, Sander L. J.
- Venue
- PLoS ONE
- Publisher
- Public Library of Science (PLoS)
- Published
- 2008-03-12
- Volume
- 3
- Issue
- 3
- Pages
- e1777
- ISSN
- 1932-6203 (ISSN-L)
- PMC
- PMC2258415
- OpenAlex
- W2086810771
- Cited by
- 135
- References
- 32
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 14 · 2022: 4 · 2021: 8 · 2020: 5 · 2019: 4 · 2018: 15 · 2017: 4 · 2016: 8 · 2015: 8 · 2014: 13 · 2013: 10 · 2012: 7
- FWCI
- 6.77
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Locations
- PLoS ONE (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, cc-by)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Research Publications (Maastricht University) (submittedVersion, cc-by)
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Thermoregulation and physiological responses
- Keywords
- mitochondrial uncoupling, skeletal muscle, adaptive thermogenesis, cold exposure, energy expenditure, state 4 respiration, brown adipose tissue, obesity treatment
- MeSH terms
- Adaptation, Physiological, Adult, Body Temperature Regulation, Cold Temperature, Energy Metabolism, Humans, Male, Mitochondria, Muscle, Muscle, Skeletal
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