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

Not Applicable

• Conditions: Mitochondrial Biogenesis

• Registration Number: NCT03975777
• Lead Sponsor: Brendon Gurd, PhD

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.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2019-05-29
• Study Start: 2019-06-01
• Study First Submitted QC: 2019-06-04
• Study First Posted: 2019-06-05
• Status Verified: 2020-03
• Last Update Submitted: 2020-03-02
• Last Update Posted: 2020-03-04
• Primary Completion: 2020-04-30
• Study Completion: 2020-04-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: Male
• Target Recruitment: 10

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

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Primary Outcome Measures

Name	Time	Method
Change in peroxisome proliferator activated receptor (PPAR) gamma co-activator 1-alpha (PGC-1α) messenger ribonucleic acid (mRNA) expression	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

Name	Time	Method
Change in PGC-1α protein content	before exercise to 1, 3, 6, 9, and 12 hours post-exercise	PGC-1α protein content
Change in Nrf2 protein content	before exercise to 1, 3, 6, 9, and 12 hours post-exercise	Nrf2 protein content
Change in LRP130 protein content	before exercise and 1, 3, 6, 9, and 12 hours post-exercise	LRP130 protein content
Change in COXI mRNA expression	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)
Change in NRF-2 mRNA expression	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.
Change in nuclear factor-erythroid 2 like 2 (Nrf2) mRNA expression	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.
Change in NRF-1 protein content	before exercise to 1, 3, 6, 9, and 12 hours post-exercise	NRF-1 protein content
Change in ND4 mRNA expression	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).
Change in PPAR-beta mRNA expression	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.
Change in estrogen related receptor (ERR)-gamma mRNA expression	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.
Change in leucine-rich pentatricopeptide repeat containing protein 130 (LRP130) mRNA expression	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
Change in mitochondrial transcription factor A (TFAM) mRNA expression	before exercise and 1, 3, 6, 9, and 12 hours post-exercise	TFAM gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes.
Change in TFAM protein content	before exercise and 1, 3, 6, 9, and 12 hours post-exercise	TFAM protein content
Change in p53 mRNA expression	before exercise to 1, 3, 6, 9, and 12 hours post-exercise	p53 gene expression. Transcription factor involved in the control of mitochondrial biogenesis.
Change in cytochrome c oxidase subunit 4 (COXIV) mRNA expression.	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)
Change in COXII mRNA expression	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).
Change in nicotinamide adenine dinucleotide (NADH) subunit 1 (ND1) mRNA expression	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)
Change in citrate synthase (CS) mRNA expression	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.
Change in nuclear respiratory factor-1 (NRF-1) mRNA expression	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.
Change in mitochondrial transcription factor B1 (TFB1M) mRNA expression	before exercise to 1, 3, 6, 9, and 12 hours post-exercise	TFB1M gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes.
Change in mitochondrial transcription factor B2 (TFB2M) mRNA expression	before exercise and 1, 3, 6, 9, and 12 hours post-exercise	TFB2M gene expression. Transcription factor controlling the expression of mitochondrial-encoded genes.

Trial Locations

Locations (1)

School of Kinesiology and Health Studies; 🇨🇦 Kingston, Ontario, Canada