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Transcriptional regulation of gene expression in human skeletal muscle during recovery from exercise
Abstract
Exercise training elicits a number of adaptive changes in skeletal muscle that result in an improved metabolic efficiency. The molecular mechanisms mediating the cellular adaptations to exercise training in human skeletal muscle are unknown. To test the hypothesis that recovery from exercise is associated with transcriptional activation of specific genes, six untrained male subjects completed 60-90 min of exhaustive one-legged knee extensor exercise for five consecutive days. On day 5, nuclei were isolated from biopsies of the vastus lateralis muscle of the untrained and the trained leg before exercise and from the trained leg immediately after exercise and after 15 min, 1 h, 2 h, and 4 h of recovery. Transcriptional activity of the uncoupling protein 3 (UCP3), pyruvate dehydrogenase kinase 4 (PDK4), and heme oxygenase-1 (HO-1) genes (relative to beta-actin) increased by three- to sevenfold in response to exercise, peaking after 1-2 h of recovery. Increases in mRNA levels followed changes in transcription, peaking between 2 and 4 h after exercise. Lipoprotein lipase and carnitine pamitoyltransferase I gene transcription and mRNA levels showed similar but less dramatic induction patterns, with increases ranging from two- to threefold. In a separate study, a single 4-h bout of cycling exercise (n = 4) elicited from 5 to >20-fold increases in UCP3, PDK4, and HO-1 transcription, suggesting that activation of these genes may be related to the duration or intensity of exercise. These data demonstrate that exercise induces transient increases in transcription of metabolic genes in human skeletal muscle. Moreover, the findings suggest that the cumulative effects of transient increases in transcription during recovery from consecutive bouts of exercise may represent the underlying kinetic basis for the cellular adaptations associated with exercise training.
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“The recovery period, which plays a central role in the development of training adaptation [19], is non optimal for prolonging the period of optimized response to the training stimulus [20].”
From Periodization of carbohydrate intake: short-term effect on performance (2016) · cites this paper as [19]
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Metadata
- Authors
- Pilegaard, H., Ordway, G. A., Saltin, B., & Neufer, P. D.
- Affiliations
- University of Copenhagen (DK)
- The University of Texas Southwestern Medical Center (US)
- Yale University (US)
- Venue
- American Journal of Physiology-Endocrinology and Metabolism
- Publisher
- American Physiological Society
- Published
- 2000-10-01
- Volume
- 279
- Issue
- 4
- Pages
- E806-E814
- ISSN
- 0193-1849 (ISSN-L)
- 1522-1555
- OpenAlex
- W2156516623
- Cited by
- 563
- References
- 45
- Citations by year
- 2026: 8 · 2025: 7 · 2024: 15 · 2023: 5 · 2022: 10 · 2021: 18 · 2020: 17 · 2019: 13 · 2018: 20 · 2017: 25 · 2016: 22 · 2015: 29 · 2014: 19 · 2013: 32 · 2012: 26
- FWCI
- 54.07
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- American Journal of Physiology-Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- National Institute of Arthritis and Musculoskeletal and Skin Diseases (AR-45372, R01AR045372)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Cardiovascular and exercise physiology
- Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Keywords
- post-exercise recovery, skeletal muscle, gene transcription, training effects, UCP3, PDK4, heme oxygenase-1, lipoprotein lipase, carnitine palmitoyltransferase 1, vastus lateralis, exercise intensity and duration, metabolic gene expression
- MeSH terms
- Uncoupling Protein 3, Actins, Adult, Carnitine O-Palmitoyltransferase, Carrier Proteins, Exercise Test, Physical Exertion, Gene Expression Regulation, Glycogen Synthase, Heme Oxygenase (Decyclizing), Hexokinase, Humans, Ion Channels, Isoenzymes, Leg, Lipoprotein Lipase, Male, Membrane Proteins, Protein Kinases, Rest, RNA, Messenger, Transcription, Genetic, Muscle, Skeletal, Mitochondrial Proteins, Heme Oxygenase-1
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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