Exercise-regulated Organ Crosstalk, Influence of IL-6
Overview
- Phase
- Not Applicable
- Intervention
- Not specified
- Conditions
- Healthy Volunteers Only
- Sponsor
- Helga Ellingsgaard
- Enrollment
- 30
- Locations
- 1
- Primary Endpoint
- Tissue specific proteomic content of EVs.
- Status
- Completed
- Last Updated
- last year
Overview
Brief Summary
Overall the study investigates organ crosstalk during exercise. More specifically, the study investigates the role of IL-6 in regulating glucose, fatty acid, and amino acid kinetics at whole body level and in skeletal muscle, liver, and brain. Furthermore, the study investigates the uptake and release of extracellular vesicles in skeletal muscle, liver, and brain in reponse to exercise.
Investigators
Helga Ellingsgaard
Principle Investigator
Rigshospitalet, Denmark
Eligibility Criteria
Inclusion Criteria
- •Minimum age: 18 years
- •Maximum age: 45 years
- •Minimum BMI: 18
- •Maximum BMI: 25
- •Sex: Male
- •Healthy (based on screening)
- •Stable body weight for 6 months
- •VO2max (mL/kg/min) ≥ 50
Exclusion Criteria
- •Thyroid disease
- •Heart disease
- •Inflammatory diseases
- •Current infection
- •Liver disease (transaminases more than 2x upper normal range)
- •Kidney disease (creatinine more than1.5 mg/dl)
- •Known immunosuppressive disease
- •Corticosteroid use
- •Regular NSAID or paracetamol usage
- •Aspirin use more than 100 mg/d
Outcomes
Primary Outcomes
Tissue specific proteomic content of EVs.
Time Frame: Comparisons between placebo and IL-6R ab are done at the end of a 1-hour exercise bout (330 minutes).
Comparing differences in proteomic content of EVs from skeletal muscle, liver, and brain in response to exercise.
Tissue specific utilization and production of substrates.
Time Frame: Comparisons between study arms are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).
Comparing, between placebo and IL-6Rab, by measuring in plasma, the Ra and Rd of substrates in muscle, liver, and brain at rest, during exercise, and recovery using the non-steady-state equations of Steele adapted for stable isotopes.
IL-6 regulation of protein synthesis and degradation.
Time Frame: Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).
Comparing differences in protein synthesis and degradation rates between placebo and IL-6Rab at rest, during exercise, and during recovery from exercise.
Size of EVs from muscle, liver, and brain.
Time Frame: Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes).
Comparing EV size deriving from skeletal muscle, liver, and brain.
EVs from muscle, liver, and brain.
Time Frame: Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes).
Comparing the content of EVs deriving from skeletal muscle, liver, and brain.
Influence of exercise on EV content.
Time Frame: Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes).
Comparing the content of EVs deriving from skeletal muscle, liver, and brain in response to exercise.
Influence of exercise on EV size
Time Frame: Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes).
Comparing EV size deriving from skeletal muscle, liver, and brain in response to exercise.
Whole body substrate kinetics.
Time Frame: Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).
Comparing rates of appearances (Ra) and disappearances (Rd) of glucose, glycerol, palmitate, amino acids between placebo and IL-6R ab at rest, during exercise, and recovery.
Number of EVs from muscle, liver, and brain.
Time Frame: Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes).
Comparing the number of EVs deriving from skeletal muscle, liver, and brain.
Influence of exercise on EV number.
Time Frame: Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes).
Comparing the number of EVs deriving from skeletal muscle, liver, and brain in response to exercise.
Secondary Outcomes
- Lactate.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Pyruvate.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Ketone bodies.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Influence of IL-6 on glucagon.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Influence of IL-6 on norepinephrine.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- IL-6 levels.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Keto acids.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Influence of IL-6 on perceived exertion.(Comparisons between placebo and IL-6R ab are done during exercise (time points 285, 300, 315, and 330 minutes).)
- Influence of IL-6 on fatty acid oxidation rates.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Influence of IL-6 on insulin.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Influence of IL-6 on epinephrine.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)
- Influence of IL-6 on substrate usage.(Comparisons between placebo and IL-6R ab are done at rest (time points 255 and 270 minutes), during exercise (time points 285, 300, 315, and 330 minutes) and during recovery from exercise (time points 345, 360, and 390 minutes).)