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Cited by 154Muscle metabolism and nutritionMetabolism, Diabetes, and CancerExercise and Physiological Responses

Substrate availability and transcriptional regulation of metabolic genes in human skeletal muscle during recovery from exercise

Pilegaard, Henriette, Osada, Takuya, Andersen, Lisbeth T., Helge, Jørn W., Saltin, Bengt, Neufer, P. Darrell·2005·Metabolism
DOI 10.1016/j.metabol.2005.03.008
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Abstract

In skeletal muscle of humans, transcription of several metabolic genes is transiently induced during recovery from exercise when no food is consumed. To determine the potential influence of substrate availability on the transcriptional regulation of metabolic genes during recovery from exercise, 9 male subjects (aged 22-27) completed 75 minutes of cycling exercise at 75% Vo2 max on 2 occasions, consuming either a high-carbohydrate (HC) or low-carbohydrate (LC) diet during the subsequent 24 hours of recovery. Nuclei were isolated and tissue frozen from vastus lateralis muscle biopsies obtained before exercise and 2, 5, 8, and 24 hours after exercise. Muscle glycogen was restored to near resting levels within 5 hours in the HC trial, but remained depressed through 24 hours in the LC trial. During the 2- to 8-hour recovery period, leg glucose uptake was 5- to 15-fold higher with HC ingestion, whereas arterial plasma free fatty acid levels were approximately 3- to 7-fold higher with LC ingestion. Exercise increased (P < .05) transcription and/or mRNA content of the pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, carnitine palmitoyltransferase I, hexokinase II, peroxisome proliferator activated receptor gamma coactivator-1 alpha, and peroxisome proliferator activated receptor alpha. Providing HC during recovery reversed the activation of pyruvate dehydrogenase kinase 4, uncoupling protein 3, lipoprotein lipase, and carnitine palmitoyltransferase I within 5 to 8 hours after exercise, whereas providing LC during recovery elicited a sustained/enhanced increase in activation of these genes through 8 to 24 hours of recovery. These findings provide evidence that factors associated with substrate availability and/or cellular metabolic recovery (eg, muscle glycogen restoration) influence the transcriptional regulation of metabolic genes in skeletal muscle of humans during recovery from exercise.

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  • Reduced post-exercise muscle glycogen availability augments expression of genes regulating substrate utilization and mitochondrial biogenesis.

    “On the basis that reduced pre- [15] and post-exercise [16] muscle glycogen availability augments expression of genes regulating substrate utilization and mitochondrial biogenesis”

    From Fuel for the Work Required: A Theoretical Framework for Carbohydrate Periodization and the Glycogen Threshold Hypothesis (2018) · cites this paper as [16]

  • Restoring post-exercise glycogen levels to > 500 mmol/kg dw attenuates exercise-induced changes in gene expression.

    “However, restoring post-exercise glycogen levels to > 500 mmol/kg dw attenuates exercise-induced changes in gene expression [16]”

    From Fuel for the Work Required: A Theoretical Framework for Carbohydrate Periodization and the Glycogen Threshold Hypothesis (2018) · cites this paper as [16]

  • Activation of metabolic genes was augmented following 75 min of cycling exercise when carbohydrate intake was restricted for over 5 h compared with controls.

    “When studying the effects on gene expression post-exercise with or without carbohydrates, interesting observations were made by Pilegaard et al. [57]: activation of metabolic genes was augmented following 75 min of cycling exercise when carbohydrate intake was restricted for over 5 h compared with controls [57].”

    From Periodized Nutrition for Athletes (2017) · cites this paper as [57]

  • The recovery period is non-optimal for prolonging the period of optimized response to the training stimulus.

    “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 [20]

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Authors
Pilegaard, H., Osada, T., Andersen, L. T., Helge, J. W., Saltin, B., & Neufer, P. D.
Affiliations
  • University of Copenhagen (DK)
  • Yale University (US)
ORCID
Venue
Metabolism
Publisher
Elsevier BV
Published
2005-08
Volume
54
Issue
8
Pages
1048-1055
ISSN
0026-0495 (ISSN-L)
DOI
10.1016/j.metabol.2005.03.008
OpenAlex
W2130919437
Cited by
154
References
42
Citations by year
2026: 1 · 2025: 5 · 2024: 7 · 2023: 2 · 2022: 5 · 2021: 9 · 2020: 7 · 2019: 8 · 2018: 12 · 2017: 8 · 2016: 9 · 2015: 11 · 2014: 4 · 2013: 6 · 2012: 3
FWCI
3.11
Type
journal article
Language
en
Open access
closed
Licence
Locations
  • 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
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Muscle metabolism and nutrition
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
  • Health Sciences › Medicine › Rehabilitation › Exercise and Physiological Responses
Keywords
post-exercise recovery, skeletal muscle, substrate availability, carbohydrate intake, muscle glycogen, glucose uptake, free fatty acids, PDK4, UCP3, lipoprotein lipase, carnitine palmitoyltransferase 1, hexokinase 2, PPARγ coactivator-1α, PPARα, vastus lateralis
MeSH terms
Forkhead Box Protein O1, Uncoupling Protein 3, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Adult, Carnitine O-Palmitoyltransferase, Carrier Proteins, DNA-Binding Proteins, Energy Metabolism, Physical Exertion, Glycogen, Glycogen Synthase, Heat-Shock Proteins, Hexokinase, Humans, Ion Channels, Lipoprotein Lipase, Male, Monosaccharide Transport Proteins, Muscle Proteins, Protein Kinases, RNA, Messenger, Transcription Factors, Transcriptional Activation, Gene Expression Regulation, Enzymologic, Muscle, Skeletal, CD36 Antigens, Recovery of Function, Mitochondrial Proteins, PPAR alpha, Glucose Transporter Type 4, Forkhead Transcription Factors

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