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

Study Overview
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Brief Summary
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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.

Official Title
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Impact of Exercise Intensity on the Time-course of Mitochondrial Biogenic Gene and Protein Expression in Human Skeletal Muscle.

Conditions
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Mitochondrial Biogenesis

Intervention / Treatment
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* Other: LO
* Other: HI


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 30 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Double


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Experimental: low-intensity exercise - high-intensity exercise<br>low-intensity exercise session followed by a high-intensity exercise session separated by a minimum of 14 days | Other: LO<br>* 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)<br>Other: HI<br>* 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)<br>|
| Experimental: high-intensity exercise - low-intensity exercise<br>high-intensity exercise session followed by a low-intensity exercise session separated by a minimum of 14 days | Other: LO<br>* 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)<br>Other: HI<br>* 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)<br>|

What is the study measuring?
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Primary Outcome Measures

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

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Change in PGC-1α protein content | PGC-1α protein content | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in nuclear factor-erythroid 2 like 2 (Nrf2) mRNA expression | Nrf2 gene expression (indirect indicator of Nrf2 activity). Transcription factor involved in the control of mitochondrial biogenesis. | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in Nrf2 protein content | Nrf2 protein content | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in PPAR-beta mRNA expression | PPAR-beta gene expression (indirect indicator of PPAR-beta activity). Transcription factor involved in the control of mitochondrial biogenesis. | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in estrogen related receptor (ERR)-gamma mRNA expression | ERR-gamma gene expression. Transcription factor involved in the control of mitochondrial biogenesis. | before exercise and 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in leucine-rich pentatricopeptide repeat containing protein 130 (LRP130) mRNA expression | LRP130 gene expression. Transcriptional co-activator and RNA-binding protein involved in the transcriptional control and stabilization of mitochondrial mRNAs | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in LRP130 protein content | LRP130 protein content | before exercise and 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in nuclear respiratory factor-1 (NRF-1) mRNA expression | NRF-1 gene expression. Transcription factor involved in the control of mitochondrial biogenesis. | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in NRF-1 protein content | NRF-1 protein content | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in mitochondrial transcription factor A (TFAM) mRNA expression | TFAM gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes. | before exercise and 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in TFAM protein content | TFAM protein content | before exercise and 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in p53 mRNA expression | p53 gene expression. Transcription factor involved in the control of mitochondrial biogenesis. | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in cytochrome c oxidase subunit 4 (COXIV) mRNA expression. | COXIV gene expression. Nuclear encoded subunit of the electron transport chain complex 4 (COX) | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in COXI mRNA expression | COXI gene expression. Mitochondrial encoded subunit of the electron transport chain complex IV (COX) | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in COXII mRNA expression | COXII gene expression.Mitochondrial encoded subunit of the electron transport chain complex IV (COX). | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in nicotinamide adenine dinucleotide (NADH) subunit 1 (ND1) mRNA expression | ND1 gene expression. Mitochondrial encoded subunit of the electron transport chain complex 1 (NADH dehydrogenase) | before exercise and 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in ND4 mRNA expression | ND4 gene expression. Mitochondrial encoded subunit of the electron transport chain complex 1 (NADH dehydrogenase). | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in citrate synthase (CS) mRNA expression | CS gene expression. The first rate limiting enzyme of the Kreb's cycle. | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in NRF-2 mRNA expression | NRF-2 gene expression. Transcription factor involved in the control of mitochondrial biogenesis. | before exercise and 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in mitochondrial transcription factor B1 (TFB1M) mRNA expression | TFB1M gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes. | before exercise to 1, 3, 6, 9, and 12 hours post-exercise | 
| Change in mitochondrial transcription factor B2 (TFB2M) mRNA expression | TFB2M gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes. | before exercise and 1, 3, 6, 9, and 12 hours post-exercise |