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

Study Overview
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Brief Summary
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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
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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.

Official Title
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Searching for Non-invasive Magnetic Resonance-based Markers for CrAT Protein Activity and Carnitine Availability in Skeletal Muscle

Conditions
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Metabolism and Nutrition Disorder, Metabolic Disturbance

Intervention / Treatment
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* Other: Exercise metabolism


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 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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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| CrAT subjects<br>13 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 | Other: Exercise metabolism<br>* Participants will perform a series of exercises inside and outside the MRS/MRI scanner.<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle PCr on-kinetic during exercise and carnitine acetyltransferase (CrAT) protein content/activity | The correlation between skeletal muscle PCr on-kinetic during one-legged exercise and CrAT protein activity will be determined. | MRS+Exercise test day 2 | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Skeletal muscle acetylcarnitine recovery after one-legged exercise and carnitine acetyltransferase (CrAT) protein content/activity | The correlation between skeletal muscle acetylcarnitine off-kinetic after one-legged exercise and CrAT protein activity will be determined. | MRS+Exercise test day 2 | 
| Skeletal muscle CrAT protein activity, from muscle biopsy, and PCr breakdown rate during one-legged exercise | The correlation between CrAT protein activity and PCr hydrolysis/breakdown will be determined | MRS+Exercise test day 1 | 
| Skeletal muscle acetylcarnitine formation capacity upon exercise and total carnitine availability in skeletal muscle | The correlation between acetylcarnitine formation upon exercise and total carnitine availability will be determined | MRS+Exercise test day 2 | 
| Skeletal muscle mitochondrial function in vitro | The association between Skeletal muscle mitochondrial function in vitro and in vivo | MRS+Exercise test day 2 | 
| Skeletal muscle oxygen availability | in vivo assessment of oxygen availability in muscle tissue upon hypoxic stimulus during resting | MRS test day 1 | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Acetylcarnitine kinetic, Phosphocreatine (PCr) kinetic