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Markers of Carnitine Acetyltransferase (CrAT) Protein Activity and Carnitine Availability

Completed
Conditions
Metabolism and Nutrition Disorder
Metabolic Disturbance
Interventions
Other: Exercise metabolism
Registration Number
NCT03697928
Lead Sponsor
Maastricht University
Brief Summary

This study aims to measure skeletal muscle metabolism in vivo during exercise using the non-invasive Magnetic Resonance Spectroscopy (MRS) technique. Specifically, phosphocreatine (PCr) kinetic and Acetylcarnitine levels will be determined at resting, during exercise and during the recovery post exercise. The target population is adult healthy men, with a wide range of maximal physical capacity.

Detailed Description

Skeletal muscle mitochondrial activation during the transition from resting metabolism to exercise may modulated by CrAT activity. Furthermore, dynamic changes in acetylcarnitine during the transition from exercise to resting metabolism (acetylcarnitine off-kinetic) may also reflect the action of CrAT protein. To date, the only possibility to get information on CrAT activity is by taking a muscle biopsy and perform enzyme activity assays ex vivo. By dynamic MRS scanning, it might be possible to deduce information that reflects CrAT activity, thereby making the biopsy sampling unnecessary.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
13
Inclusion Criteria
  • Males, Generally healthy
  • Age 18-40 years old
  • BMI 18 - 25 kg/m2
  • No medication use that interfere with the aims of the study
  • Stable level of daily physical activity or training for at least 6 months
Exclusion Criteria
  • Females
  • Regular smokers, drug abuse
  • Participation in other studies
  • Weight gain/loss > 3 kg in the last 6 months
  • Contraindications for MRS scans:
  • Vegetarian eating behavior

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
CrAT subjectsExercise metabolism13 healthy adult men, with a wide range of maximal aerobic capacity will be included. Subjects will be classified as trained, physical active and untrained according to their VO2max. Subject will perform one-legged knee extension and flexion exercise inside the MRS scanner and cycling outside the scanner
Primary Outcome Measures
NameTimeMethod
Skeletal muscle PCr on-kinetic during exercise and carnitine acetyltransferase (CrAT) protein content/activityMRS+Exercise test day 2

The correlation between skeletal muscle PCr on-kinetic during one-legged exercise and CrAT protein activity will be determined.

Secondary Outcome Measures
NameTimeMethod
Skeletal muscle acetylcarnitine recovery after one-legged exercise and carnitine acetyltransferase (CrAT) protein content/activityMRS+Exercise test day 2

The correlation between skeletal muscle acetylcarnitine off-kinetic after one-legged exercise and CrAT protein activity will be determined.

Skeletal muscle oxygen availabilityMRS test day 1

in vivo assessment of oxygen availability in muscle tissue upon hypoxic stimulus during resting

Skeletal muscle CrAT protein activity, from muscle biopsy, and PCr breakdown rate during one-legged exerciseMRS+Exercise test day 1

The correlation between CrAT protein activity and PCr hydrolysis/breakdown will be determined

Skeletal muscle acetylcarnitine formation capacity upon exercise and total carnitine availability in skeletal muscleMRS+Exercise test day 2

The correlation between acetylcarnitine formation upon exercise and total carnitine availability will be determined

Skeletal muscle mitochondrial function in vitroMRS+Exercise test day 2

The association between Skeletal muscle mitochondrial function in vitro and in vivo

Trial Locations

Locations (1)

Maastricht University

🇳🇱

Maastricht, Limburg, Netherlands

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