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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Placebo | Placebo Comparator | Saline infusion |
|
| Tocilizumab | Experimental | IL-6 receptor antibody infusion (8 mg/kg body weight, max 800 mg) |
|
| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| exercise | Other | acute exercise bout |
|
| Measure | Description | Time Frame |
|---|---|---|
| Whole body substrate kinetics. | 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. | 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). |
| Tissue specific utilization and production of substrates. | 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. | 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). |
| IL-6 regulation of protein synthesis and degradation. | Comparing differences in protein synthesis and degradation rates between placebo and IL-6Rab at rest, during exercise, and during recovery from exercise. | 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). |
| Number of EVs from muscle, liver, and brain. | Comparing the number of EVs deriving from skeletal muscle, liver, and brain. | Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes). |
| Size of EVs from muscle, liver, and brain. | Comparing EV size deriving from skeletal muscle, liver, and brain. |
| Measure | Description | Time Frame |
|---|---|---|
| Lactate. | Differences in plasma lactate from skeletal muscle, liver, and brain comparing placebo and IL-6R ab. | 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). |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Helga Ellingsgaard, PhD | Rigshospitalet, Denmark | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| Rigshospitalet | Copenhagen | Capital Region | 2100 | Denmark |
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| ID | Term |
|---|---|
| D009043 | Motor Activity |
| ID | Term |
|---|---|
| D001519 | Behavior |
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| ID | Term |
|---|---|
| D015444 | Exercise |
| ID | Term |
|---|---|
| D009043 | Motor Activity |
| D009068 | Movement |
| D009142 | Musculoskeletal Physiological Phenomena |
| D055687 | Musculoskeletal and Neural Physiological Phenomena |
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| Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes). |
| EVs from muscle, liver, and brain. | Comparing the content of EVs deriving from skeletal muscle, liver, and brain. | Comparisons between placebo and IL-6R ab are done before exercise (time points 255 and 270 minutes). |
| Influence of exercise on EV number. | Comparing the number of EVs deriving from skeletal muscle, liver, and brain in response to exercise. | Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes). |
| Influence of exercise on EV size | Comparing EV size deriving from skeletal muscle, liver, and brain in response to exercise. | Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes). |
| Influence of exercise on EV content. | Comparing the content of EVs deriving from skeletal muscle, liver, and brain in response to exercise. | Comparisons between placebo and IL-6R ab are done throughout a 1-hour exercise bout (time points 285, 300, 315, and 330 minutes). |
| Tissue specific proteomic content of EVs. | Comparing differences in proteomic content of EVs from skeletal muscle, liver, and brain in response to exercise. | Comparisons between placebo and IL-6R ab are done at the end of a 1-hour exercise bout (330 minutes). |
| Pyruvate. |
Differences in plasma pyruvate from skeletal muscle, liver, and brain comparing placebo and IL-6R ab. |
| 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. | Differences in plasma keto acids from skeletal muscle, liver, and brain comparing placebo and IL-6R ab. | 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. | Differences in plasma ketone bodies from skeletal muscle, liver, and brain comparing placebo and IL-6R ab. | 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 fatty acid oxidation rates. | Comparing, between placebo and IL-6R ab, differences in fatty acid, e.g. palmitate oxidation rates, at whole body level and in skeletal muscle, liver, and brain. | 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. | Comparing differences in plasma insulin concentrations between placebo and IL-6R ab. | 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. | Comparing differences plasma glucagon concentrations between placebo and IL-6R ab. | 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. | Comparing differences in plasma epinephrine concentrations between placebo and IL-6R ab. | 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. | Comparing differences in plasma norepinephrine concentrations between placebo and IL-6R ab. | 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. | Comparing differences in plasma IL-6 concentrations between placebo and IL-6R ab. | 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. | Differences in respiratory exchange ratio comparing placebo and IL-6R ab. | 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. | Differences in rate of perceived exertion during exercise comparing placebo and IL-6R ab. | Comparisons between placebo and IL-6R ab are done during exercise (time points 285, 300, 315, and 330 minutes). |