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

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.

Full Title of Study: “Searching for Non-invasive Magnetic Resonance-based Markers for CrAT Protein Activity and Carnitine Availability in Skeletal Muscle”

Study Type

  • Study Type: Observational
  • Study Design
    • Time Perspective: Cross-Sectional
  • Study Primary Completion Date: February 1, 2020

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.

Interventions

  • Other: Exercise metabolism
    • Participants will perform a series of exercises inside and outside the MRS/MRI scanner.

Arms, Groups and Cohorts

  • CrAT subjects
    • 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

Clinical Trial Outcome Measures

Primary Measures

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

Secondary Measures

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

Participating in This Clinical Trial

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

Gender Eligibility: Male

Minimum Age: 18 Years

Maximum Age: 40 Years

Are Healthy Volunteers Accepted: Accepts Healthy Volunteers

Investigator Details

  • Lead Sponsor
    • Maastricht University
  • Provider of Information About this Clinical Study
    • Sponsor
  • Overall Official(s)
    • Vera Schrauwen-Hinderling, Phd, Principal Investigator, Maastricht University

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