Increased uncoupling protein 3 content does not affect mitochondrial function in human skeletal muscle in vivo
Open accessAbstract
Phosphocreatine (PCr) resynthesis rate following intense anoxic contraction can be used as a sensitive index of in vivo mitochondrial function. We examined the effect of a diet-induced increase in uncoupling protein 3 (UCP3) expression on postexercise PCr resynthesis in skeletal muscle. Nine healthy male volunteers undertook 20 one-legged maximal voluntary contractions with limb blood flow occluded to deplete muscle PCr stores. Exercise was performed following 7 days consumption of low-fat (LF) or high-fat (HF) diets. Immediately following exercise, blood flow was reinstated, and muscle was sampled after 20, 60, and 120 seconds of recovery. Mitochondrial coupling was assessed by determining the rate of PCr resynthesis during recovery. The HF diet increased UCP3 protein content by approximately 44% compared with the LF diet. However, this HF diet-induced increase in UCP3 expression was not associated with any changes in the rate of muscle PCr resynthesis during conditions of maximal flux through oxidative phosphorylation. Muscle acetylcarnitine, free-creatine, and lactate concentrations during recovery were unaffected by the HF diet. Taken together, our findings demonstrate that increasing muscle UCP3 expression does not diminish the rate of PCr resynthesis, allowing us to conclude that the primary role of UCP3 in humans is not uncoupling.
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UCP3 is upregulated under conditions of increased free fatty acid delivery to mitochondria, including fasting, insulin-deficient diabetes, and high-fat feeding.
“UCP3 is known to be upregulated under conditions of increased free fatty acid delivery to mitochondria, including fasting (44), insulin-deficient diabetes (134), and high-fat feeding (135).”
From Mitochondrial Dysfunction in Diabetes: From Molecular Mechanisms to Functional Significance and Therapeutic Opportunities (2010) · cites this paper as [135]
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- Authors
- Hesselink, M. K. C., Greenhaff, P. L., Constantin-Teodosiu, D., Hultman, E., Saris, W. H. M., Nieuwlaat, R., Schaart, G., Kornips, E., & Schrauwen, P.
- Affiliations
- Maastricht University (NL)
- Queen's Medical Centre (GB)
- Karolinska Institutet (SE)
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2003-02-15
- Volume
- 111
- Issue
- 4
- Pages
- 479-486
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC152374
- OpenAlex
- W2130962964
- Cited by
- 82
- References
- 52
- Citations by year
- 2024: 1 · 2023: 1 · 2022: 2 · 2021: 2 · 2019: 1 · 2018: 1 · 2016: 2 · 2015: 1 · 2014: 3 · 2013: 2 · 2012: 3
- FWCI
- 4.60
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Journal of Clinical Investigation (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Complementary and alternative medicine › Cardiovascular and exercise physiology
- Keywords
- UCP3, mitochondrial uncoupling, skeletal muscle, phosphocreatine resynthesis, high-fat diet, mitochondrial coupling, oxidative phosphorylation, creatine kinase, acetyl-L-carnitine, lactate, post-exercise recovery
- MeSH terms
- Uncoupling Protein 3, Adult, Carrier Proteins, Creatine, Dietary Fats, Fatty Acids, Proton-Translocating ATPases, Humans, Ion Channels, Male, Mitochondria, Muscle, Muscle Contraction, Oxidative Phosphorylation, Phosphocreatine, Uncoupling Agents, Muscle, Skeletal, Lactic Acid, Mitochondrial Proteins
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