Effects of Acute Exercise on Acetylcarnitine Concentration in Endurance Trained and Untrained Subjects

Study Overview
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Brief Summary
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It has been suggested that imbalance between TCA-cycle flux and β-oxidation may underlie insulin resistance, a predisposing factor for the development of type 2 diabetes mellitus. Acetylcarnitine concentration is suggested to be a marker of such imbalance. It is expected that when TCA-cycle capacity is high (a high oxidative capacity), less acetylcarnitine will accumulate, because of an improved balance between supply and demand of lipids. The major research objective is to examine if acute exercise results in a more pronounced increase in acetylcarnitine concentration in sedentary subjects compared to endurance-trained subjects and if the exercise-induced increase in acetylcarnitine is restored more quickly in endurance-trained subjects when compared to sedentary subjects. The investigators hypothesize that the increase in acetylcarnitine levels will be lower in trained subjects when compared to sedentary subjects, due to a better balance between lipid supply and utilization by the TCA-cycle. Furthermore it is expected that acetylcarnitine concentrations will be restored faster in these trained subjects, because of a tighter regulation of influx of fatty acids. To test this hypothesis the investigators want to compare the acetylcarnitine response to exercise in a group of sedentary subjects and a group of endurance trained subjects. This response will be measured for 30 minutes after exercise with the use of 1H-MRS.

Official Title
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Effects of Acute Exercise on Acetylcarnitine Concentration in Endurance Trained and Untrained Subjects

Conditions
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Diabetes Mellitus, Type 2

Intervention / Treatment
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* Other: Cycling


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Normal weight (BMI 18-25 kg/m2) Healthy Stable dietary habits No use of medication VO2-max for trained subjects above 50 mL/min/kg VO2-max for untrained subjects below 40 mL/min/kg Exclusion Criteria: Any medical condition requiring treatment and/or medication use OR diminishing exercise tolerance Alcohol consumption of more than 20 g per day (± 2 units) Unstable body weight (weight gain or loss > 3 kg in the past three months) Participation in another biomedical study within 1 month prior to the screening visit Contraindications for MRI scan: Central nervous system aneurysm clips Implanted neural stimulator Implanted cardiac pacemaker of defibrillator Cochlear implant Iron- containing corpora aliena in the eye or brain Hearing aids and artificial (heart) valves which is contraindicated for MRS Subjects, who do not want to be informed about unexpected medical findings cannot participate in the study.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 40 Years

Sexes Eligible for Study
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All

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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Design Details

Primary Purpose: Basic Science
Allocation: Non-Randomized
Intervention Model: Parallel Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Other: Endurance Trained Subjects<br> | Other: Cycling<br>* 30 minutes of cycling at 50% of predetermined maximal performance<br>|
| Other: Untrained Subjects<br> | Other: Cycling<br>* 30 minutes of cycling at 50% of predetermined maximal performance<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Exercise-induced changes in acetylcarnitine concentrations and dynamics of acetylcarnitine restoration after exercise | Acetylcarnitine concentration measured with Proton Magnetic Resonance Spectroscopy (1H-MRS) | During 30 minutes prior to the exercise and for 30 minutes after exercise | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Substrate oxidation | Measured with indirect calorimetry | Measured during the 30 minutes of exercise | 
| Blood plasma free fatty acids | Blood sample of 10 mL | At the start and at the end of 30 minutes of exercise | 
| Blood plasma triglycerides | Blood sample of 10 mL | At the start and at the end of 30 minutes of exercise | 
| Blood plasma glucose | Blood sample of 10 mL | At the start and at the end of 30 minutes of exercise |