Exercise, Gene Expression, Muscle, Myokine
Conditions
Brief summary
Rationale: Proteins released from muscle during and shortly after exercise, often referred to as myokines, may be central to our understanding of the cross-talk during and after exercise between skeletal muscles and other organs, in particular the liver. So far only a few myokines are identified (e.g. IL-6, IL-8, IL-15, TNF-alpha). Taking into account the role of these several known myokines in developing insulin resistance, revealing new putative myokines might provide valuable information and a direction for future research on the pathogenesis and treatment of type 2 diabetes mellitus. Objective: The objective of the present study is to identify novel myokines, expression of which is altered in skeletal muscle after a single bout of exercise. Study design: experimental study. Study population: Ten healthy, male subjects between 40 and 60 years of age and BMI \< 30 kg/m2, will participate in this study. Intervention: A single exercise bout that consists of one hour one-legged cycling on a adapted recumbent cycle ergometer at a submaximal rate. The non-exercising leg will serve as control for the exercising leg. Main study outcomes: Main study outcomes include upregulation of genes in skeletal muscle after exercise (with a focus on genes encoding myokines) and changes of blood plasma levels of selected proteins after exercise.
Interventions
OTHERSingle legged exercise
A single exercise bout that consists of one hour one-legged cycling on a adapted recumbent cycle ergometer at a submaximal rate. The non-exercising leg will serve as control for the exercising leg.
Sponsors
Dutch Diabetes Research Foundation
Wageningen University
Study design
Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE
Eligibility
Sex/Gender
MALE
Age
40 Years to 60 Years
Healthy volunteers
Yes
Inclusion criteria
* Age 40-60 years * Male gender * BMI \< 30 kg/m2
Exclusion criteria
* Exercising regularly (\> 2 times a week, \> 3 hour in total per week) * Unstable body weight (weight gain or loss \> 3 kg in the past three months) * Following, or have recently followed a (weight-loss) diet * Donated or intended to donate blood 2 months before until two months after the study * Medical condition that can interfere with the study outcome (i.e. cardiovascular disease, pulmonary disease) * Systolic blood pressure \>160 mmHg and/or diastolic blood pressure \>100 mmHg * Use of medications known to interfere with gene expression in the muscles (i.e. statins, fenofibrate). * Use of antithrombotic therapy (marcoumar, sintromitis). * Diagnosed diabetes mellitus type 1 or 2. * Drugs or alcohol abuse ( \> 3 glasses of alcoholic beverages a day). * (Chronic) injuries of the locomotor system that can interfere with the intervention * Participated in another study within the last six months
Design outcomes
Primary
| Measure | Time frame | Description |
|---|---|---|
| Gene expression changes in skeletal muscle from baseline to after exercise | T = 0 and T =1 | Gene expression is measured using whole genome Affymatrix microarrays Muscle tissue will be collected at time points T = 0 (before exercise) and T = 1 (directly after exercise). Special focus is on the changes in genes coding for myokines. Up to 5 genes will be selected for follow-up analysis. |
| Changes in plasma levels of selected proteins | T = 0, T =1 and T = 3 | Selected proteins will be analyzed by ELISA assays or western blot analysis, depending on ELISA availability at T = 0, T = 1 and T = 3 (2 hours post-exercise). The selection of the proteins is based on significance, the robustness of induction (\>80% of subjects showing induction) and the magnitude of the induction ( mean fold change \> 2) |
Secondary
| Measure | Time frame | Description |
|---|---|---|
| PBMC gene expression changes before and after exercise | T = 0, T = 1 and T =3 | Gene expression changes in the blood will be assessed using whole genome Affymetrix microarrays for the samples at T = 0, 1 and 3. |
| Routine plasma level changes before and after exercise | T = 0, 1 and 3 | At all three time point (T = 0, 1 and 3) plasma levels of glucose, insulin, fatty acids, triglycerides, cortisol, adrenalin and lactate will be determined. |
| Heart rate changes, baseline compared with exercise | During the intervention | Heart rate will be measured during the maximum work load test and the experimental exercise period. |
Countries
Netherlands
Outcome results
None listed