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Time-course of Mitochondrial Biogenic Gene and Protein Expression in Exercised Human Skeletal Muscle

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ClinicalTrials.gov Identifier: NCT03975777
Recruitment Status : Recruiting
First Posted : June 5, 2019
Last Update Posted : June 17, 2019
Sponsor:
Information provided by (Responsible Party):
Brendon Gurd, Queen's University

Brief Summary:
This study examines the impact of exercise intensity on the 12-hour time-course of mitochondrial biogenic gene and protein expression in human skeletal muscle. Briefly, participants will perform two experimental sessions involving an acute bout of work-matched low- or high-intensity interval cycling exercise in a randomized crossover fashion, two weeks apart. Skeletal muscle biopsies will be obtained from the vastus lateralis (3 from each leg) before and 1, 3, 6, 9, and 12 hours post-exercise. Changes in the expression of various transcription factors and mitochondrial proteins will be examined at the mRNA and protein level to determine the time-course of changes in these factors differs between exercise protocols of different intensities.

Condition or disease Intervention/treatment Phase
Mitochondrial Biogenesis Other: LO Other: HI Not Applicable

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Study Type : Interventional  (Clinical Trial)
Estimated Enrollment : 10 participants
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double (Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Impact of Exercise Intensity on the Time-course of Mitochondrial Biogenic Gene and Protein Expression in Human Skeletal Muscle.
Actual Study Start Date : June 1, 2019
Estimated Primary Completion Date : October 30, 2019
Estimated Study Completion Date : October 30, 2019

Resource links provided by the National Library of Medicine


Arm Intervention/treatment
Experimental: low-intensity exercise - high-intensity exercise
low-intensity exercise session followed by a high-intensity exercise session separated by a minimum of 14 days
Other: LO
Participants will perform an acute bout of low-intensity cycling (11 x 1 min intervals at ~73% of peak aerobic work rate interspersed with 1 min recovery periods)

Other: HI
Participants will perform an acute bout of high-intensity cycling (8 x 1 min intervals at ~100% of peak aerobic work rate interspersed with 1 min recovery periods)

Experimental: high-intensity exercise - low-intensity exercise
high-intensity exercise session followed by a low-intensity exercise session separated by a minimum of 14 days
Other: LO
Participants will perform an acute bout of low-intensity cycling (11 x 1 min intervals at ~73% of peak aerobic work rate interspersed with 1 min recovery periods)

Other: HI
Participants will perform an acute bout of high-intensity cycling (8 x 1 min intervals at ~100% of peak aerobic work rate interspersed with 1 min recovery periods)




Primary Outcome Measures :
  1. Change in peroxisome proliferator activated receptor (PPAR) gamma co-activator 1-alpha (PGC-1α) messenger ribonucleic acid (mRNA) expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    PGC-1α gene expression (indirect indicator of PGC-1α activity). Transcriptional co-activator involved in the control of mitochondrial biogenesis.


Secondary Outcome Measures :
  1. Change in PGC-1α protein content [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    PGC-1α protein content

  2. Change in nuclear factor-erythroid 2 like 2 (Nrf2) mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    Nrf2 gene expression (indirect indicator of Nrf2 activity). Transcription factor involved in the control of mitochondrial biogenesis.

  3. Change in Nrf2 protein content [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    Nrf2 protein content

  4. Change in PPAR-beta mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    PPAR-beta gene expression (indirect indicator of PPAR-beta activity). Transcription factor involved in the control of mitochondrial biogenesis.

  5. Change in PPAR-beta protein content [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    PPAR-beta protein content

  6. Change in estrogen related receptor (ERR)-gamma mRNA expression [ Time Frame: before exercise and 1, 3, 6, 9, and 12 hours post-exercise ]
    ERR-gamma gene expression. Transcription factor involved in the control of mitochondrial biogenesis.

  7. Change in ERR-gamma protein content [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    ERR-gamma protein content

  8. Change in leucine-rich pentatricopeptide repeat containing protein 130 (LRP130) mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    LRP130 gene expression. Transcriptional co-activator and RNA-binding protein involved in the transcriptional control and stabilization of mitochondrial mRNAs

  9. Change in LRP130 protein content [ Time Frame: before exercise and 1, 3, 6, 9, and 12 hours post-exercise ]
    LRP130 protein content

  10. Change in nuclear respiratory factor-1 (NRF-1) mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    NRF-1 gene expression. Transcription factor involved in the control of mitochondrial biogenesis.

  11. Change in NRF-1 protein content [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    NRF-1 protein content

  12. Change in mitochondrial transcription factor A (TFAM) mRNA expression [ Time Frame: before exercise and 1, 3, 6, 9, and 12 hours post-exercise ]
    TFAM gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes.

  13. Change in TFAM protein content [ Time Frame: before exercise and 1, 3, 6, 9, and 12 hours post-exercise ]
    TFAM protein content

  14. Change in p53 mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    p53 gene expression. Transcription factor involved in the control of mitochondrial biogenesis.

  15. Change in cytochrome c oxidase subunit 4 (COXIV) mRNA expression. [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    COXIV gene expression. Nuclear encoded subunit of the electron transport chain complex 4 (COX)

  16. Change in COXI mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    COXI gene expression. Mitochondrial encoded subunit of the electron transport chain complex IV (COX)

  17. Change in COXII mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    COXII gene expression.Mitochondrial encoded subunit of the electron transport chain complex IV (COX).

  18. Change in nicotinamide adenine dinucleotide (NADH) subunit 1 (ND1) mRNA expression [ Time Frame: before exercise and 1, 3, 6, 9, and 12 hours post-exercise ]
    ND1 gene expression. Mitochondrial encoded subunit of the electron transport chain complex 1 (NADH dehydrogenase)

  19. Change in ND4 mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    ND4 gene expression. Mitochondrial encoded subunit of the electron transport chain complex 1 (NADH dehydrogenase).

  20. Change in citrate synthase (CS) mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    CS gene expression. The first rate limiting enzyme of the Kreb's cycle.

  21. Change in NRF-2 mRNA expression [ Time Frame: before exercise and 1, 3, 6, 9, and 12 hours post-exercise ]
    NRF-2 gene expression. Transcription factor involved in the control of mitochondrial biogenesis.

  22. Change in mitochondrial transcription factor B1 (TFB1M) mRNA expression [ Time Frame: before exercise to 1, 3, 6, 9, and 12 hours post-exercise ]
    TFB1M gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes.

  23. Change in mitochondrial transcription factor B2 (TFB2M) mRNA expression [ Time Frame: before exercise and 1, 3, 6, 9, and 12 hours post-exercise ]
    TFB2M gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes.



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Ages Eligible for Study:   18 Years to 30 Years   (Adult)
Sexes Eligible for Study:   Male
Accepts Healthy Volunteers:   Yes
Criteria

Inclusion Criteria:

  • recreationally active (no more than three hours of structured weekly physical activity)
  • not currently involved in a systematic training program for improving cardiorespiratory fitness, muscular strength, and/or sport-specific skills
  • body mass index < 30 kg/m2

Exclusion Criteria:

  • presence of cardiometabolic disease
  • taking regular prescription medication for the treatment of cardiometabolic disease
  • current cigarette smoker

Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT03975777


Contacts
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Contact: Hashim Islam, MSc 4037954125 16mhi@queensu.ca

Locations
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Canada, Ontario
School of Kinesiology and Health Studies Recruiting
Kingston, Ontario, Canada, K7L3N6
Contact: Hashim Islam, MSc    4037954125    16mhi@queensu.ca   
Sponsors and Collaborators
Queen's University
Investigators
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Principal Investigator: Brendon J. Gurd, PhD School of Kinesiology and Health Studies

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Responsible Party: Brendon Gurd, Associate Professor, Queen's University
ClinicalTrials.gov Identifier: NCT03975777     History of Changes
Other Study ID Numbers: QMPL-TC-19
First Posted: June 5, 2019    Key Record Dates
Last Update Posted: June 17, 2019
Last Verified: June 2019
Individual Participant Data (IPD) Sharing Statement:
Plan to Share IPD: No

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Studies a U.S. FDA-regulated Drug Product: No
Studies a U.S. FDA-regulated Device Product: No