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Effect of Exercise on the Human Skeletal Muscle Phosphoproteome

Effect of Exercise on the Human Skeletal Muscle Phosphoproteome

Status
Completed
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT04263714
Enrollment
16
Registered
2020-02-11
Start date
2020-04-01
Completion date
2024-05-01
Last updated
2024-11-21

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Skeletal Muscle Protein Synthesis

Brief summary

Generally, resistance exercise increases muscle mass and strength, and fatigue resistance. How resistance exercise achieves these adaptations remains understudied, but what is known is that skeletal muscle translates the physical and biochemical stresses of resistance exercise into morphological and metabolic adaptations. While resistance exercise activates signaling pathways (i.e., proteins) that increase the synthesis of specific proteins to cause adaptations, thousands of proteins are likely involved, and their interactions are complicated. The investigators aim to study these processes.

Detailed description

Skeletal muscle is a highly plastic tissue, capable of adapting to changes in nutritional intake and contractile activity. For instance, resistance exercise results in a mild stimulation of rates of muscle protein breakdown (MPB) but a greater stimulation of the rates of muscle protein synthesis (MPS). When resistance exercise is performed prior to protein ingestion there is a synergistic combination of the two stimuli such that rates of MPS are stimulated over and above those of MPB. Thus, repeated bouts of resistance exercise, when coupled with protein ingestion, result in the accretion of skeletal muscle protein referred to as hypertrophy. Importantly, by changing the nature of the exercise stimulus, it is possible to redirect the focus of the type of skeletal muscle proteins that are being synthesized. For example, prolonged and repeated lower-load dynamic stimulation of skeletal muscle (i.e., endurance exercise training) results in an increase in the expression of mitochondrial genes, proteins, and ultimately enhanced mitochondrial content, leading to a shift towards an oxidative phenotype, and improved fatigue resistance. Resistance exercise training also stimulates the transcription of genes and accrual of new muscle proteins, but these genes and proteins are largely associated with the myofibrillar protein fraction, and regular resistance exercise leads to muscle hypertrophy and increased force-generating capacity. However, during the early stages of exercise training, particularly in training-naïve participants there is a significant increase in the expression of genes common to both modalities of exercise. It is only with sustained exercise training that there is a 'fine-tuning' of the transcriptome, the protein synthetic response, and then the proteome that gives rise to divergent hypertrophic and oxidative phenotypes.

Interventions

BEHAVIORALExercise

Aerobic exercise and resistance exercise

Sponsors

McMaster University
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE

Intervention model description

Aerobic and resistance exercise

Eligibility

Sex/Gender
ALL
Age
18 Years to 30 Years
Healthy volunteers
Yes

Inclusion criteria

\- between the ages of 18 and 30 years

Exclusion criteria

* Smoker or user of tobacco products; * High physical activity * Have health problems such as: renal or gastrointestinal disorders, metabolic disease, heart disease, vascular disease, rheumatoid arthritis, diabetes, poor lung function, uncontrolled blood pressure, dizziness, thyroid problems, or any other health conditions for which you are being treated that might put you at risk for this study; * Taking anti-diabetic, anti-inflammatory, platelet inhibitor, or anti-coagulant medications; * Use of an investigational drug product within the last 30 days; * Have participated in an infusion protocol in the last year; or * Do not understand English or have a condition the PI believes would interfere with a participants' ability to provide informed consent, comply with the study protocol, or which might confound the interpretation of the study results or put someone at undue risk.

Design outcomes

Primary

MeasureTime frameDescription
Change in Acute Muscle Protein SynthesisPre exercise (resting) to 3 hours post-exerciseMyofibrillar and intracellular enrichments of L-\[ring- 13C6\] phenylalanine will be measured. MPS will be calculated using the precursor-product equation: MPS =(\[E2b-E1b\]/\[Eic x t\]) x 100. Eb represents the enrichment of bound myofibrillar protein, Eic is the average intracellular enrichment between two biopsies, and t is the tracer incorporation time in h. As we will employ 'tracer naïve' participants (had not previously participated in a study protocol where L-\[ring- 13C6\] phenylalanine was infused), a pre-infusion blood sample will be used for the calculation of resting myofibrillar MPS. The outcomes measure will be expressed as a percentage change of MPS relative to the baseline measure. i.e. intracellular enrichment of L-\[ring- 13C6\] phenylalanine relative to the baseline (resting) period.

Countries

Canada

Participant flow

Participants by arm

ArmCount
Exercise
All subjects will perform both aerobic and resistance exercise Exercise: Aerobic exercise and resistance exercise
16
Total16

Baseline characteristics

CharacteristicExercise
Age, Customized
Age
21 Years
Muscle Protein Synthesis
Cohort 1
0.041 Protein synthesis (% / hour)
STANDARD_DEVIATION 0.007
Muscle Protein Synthesis
Cohort 2
0.027 Protein synthesis (% / hour)
STANDARD_DEVIATION 0.004
Race and Ethnicity Not Collected— Participants
Sex: Female, Male
Female
6 Participants
Sex: Female, Male
Male
10 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
0 / 16
other
Total, other adverse events
0 / 16
serious
Total, serious adverse events
0 / 16

Outcome results

Primary

Change in Acute Muscle Protein Synthesis

Myofibrillar and intracellular enrichments of L-\[ring- 13C6\] phenylalanine will be measured. MPS will be calculated using the precursor-product equation: MPS =(\[E2b-E1b\]/\[Eic x t\]) x 100. Eb represents the enrichment of bound myofibrillar protein, Eic is the average intracellular enrichment between two biopsies, and t is the tracer incorporation time in h. As we will employ 'tracer naïve' participants (had not previously participated in a study protocol where L-\[ring- 13C6\] phenylalanine was infused), a pre-infusion blood sample will be used for the calculation of resting myofibrillar MPS. The outcomes measure will be expressed as a percentage change of MPS relative to the baseline measure. i.e. intracellular enrichment of L-\[ring- 13C6\] phenylalanine relative to the baseline (resting) period.

Time frame: Pre exercise (resting) to 3 hours post-exercise

ArmMeasureGroupValue (MEAN)Dispersion
ExerciseChange in Acute Muscle Protein SynthesisMyofibrillar Protein Synthesis143 percent changeStandard Deviation 53
ExerciseChange in Acute Muscle Protein SynthesisSarcoplasmic Protein Synthesis123 percent changeStandard Deviation 115

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026