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

Maastricht University13 enrolled

Overview

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.

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.

Study Type

OBSERVATIONAL

Enrollment

Conditions

Metabolism and Nutrition Disorder Metabolic Disturbance

Interventions

Exercise metabolismOTHER

Participants will perform a series of exercises inside and outside the MRS/MRI scanner.

Eligibility

Sex: MALEMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

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

Locations (1)

Maastricht University

Maastricht, Limburg, Netherlands

Outcomes

Primary Outcomes

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.

Time frame: MRS+Exercise test day 2

Secondary Outcomes

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.

Time frame: 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

Time frame: 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

Time frame: MRS+Exercise test day 2

Skeletal muscle mitochondrial function in vitro

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

Time frame: MRS+Exercise test day 2

Skeletal muscle oxygen availability

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

Time frame: MRS test day 1

Data from ClinicalTrials.gov

This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.