IL-6 Regulation of Energy Stores During Recovery From an Acute Exercise Bout

Helga Ellingsgaard30 enrolled

Overview

The aim of the study is to investigate the role of exercise-induced IL-6 in regulating energy stores and energy metabolism during recovery after an acute exercise bout. To achieve this, 30 men will be randomized to infusion placebo or tocilizumab (IL-6 receptor antibody) combined with a 2-hour exercise bout. Stable isotope tracers will be infused to determine substrate kinetics. Indirect calorimetry will be applied to determine substrate oxidation, and muscle biopsies will be taken to determine substrate uptake and storage.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

DOUBLE

Enrollment

Conditions

Glycogen Depletion

Interventions

Tocilizumab/Actemra® (Roche)DRUG

The infusion of tocilizumab will antagonize IL-6 signaling for the duration of the study, allowing us to determine the role of IL-6 in regulating energy stores following acute exercise

Saline 9%DRUG

The infusion of saline will serve as placebo for tocilizumab, allowing us to determine the role of IL-6 in regulating energy stores following acute exercise

Eligibility

Sex: MALEMin age: 18 YearsMax age: 40 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Physically active (defined as meeting the ACSM's guidelines of 2.5h per week of moderate to vigorous physical activity per week), young, healthy males will be included. Participants may be included in the study if they meet all the following criteria: * Age ≥ 18 years and ≤ 40 years * BMI \< 18 and \> 25 kg/m2 * Healthy (based on screening) * Stable body weight for 6 months * ≥ 2.5h/week moderate to vigorous physical activity Exclusion Criteria: * • Cardiovascular disease * Rheumatologic disease * Metabolic disease * Elite sports or high aerobic training status (VO2max \> 60 mL O2/min/kg) * Frequent/chronic use of medications affecting physical performance or inflammation (NSAIDS, DMARDS, corticosteroids) * Aspirin use \>100 mg/d * Thyroid disease * Current infection * Aspartate amino transferase (AST) or alanine amino transferase (ALT) \>2x upper normal range * History of carcinoma * History of tuberculosis * Ketogenic diet * Smoking * Anemia (hematocrit \<33%) * Neutrophil count \<0,5x 109/l * Thrombocytes \<50x 109/l or bleeding disorders

Locations (1)

Centre for Physical Activity Research, Rigshospitalet Section 7641

Copenhagen, Capital Region, Denmark

Outcomes

Primary Outcomes

Change in muscle glycogen content (mmol/kg/h)

Comparing change in muscle glycogen in the two groups from before exercise to immediately after exercise, and after 1 hour and 4 hours of recovery

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in muscle triglycerides content

Comparing change in muscle triglycerides in the two groups from before exercise to immediately after exercise, and after 1 hour and 4 hours of recovery

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in muscle expression of glucose transporter type 4 (GLUT4)

Comparing muscle expression of GLUT4 before and immediately after exercise and 4 hours after recovery in the two groups

Time frame: Measured at 0, 120 and 360 min

Change in muscle expression of fatty acid translocase (FAT/CD36)

Comparing muscle expression of FAT/CD36 before and immediately after exercise and 4 hours after recovery in the two groups

Time frame: Measured at 0, 120 and 360 min

Change in muscle expression of muscle fatty acid binding protein (FABPm)

Comparing muscle expression of FABPm before and immediately after exercise and 4 hours after recovery in the two groups

Time frame: Measured at 0, 120 and 360 min

Change in muscle expression of fatty acid transporter 4 (FATP4)

Comparing muscle expression of FATP4 before and immediately after exercise and 4 hours after recovery in the two groups

Time frame: Measured at 0, 120 and 360 min

Change in muscle expression of glycerol transporters

Comparing muscle expression of glycerol transporters before and immediately after exercise and 4 hours after recovery in the two groups

Data from ClinicalTrials.gov

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Secondary Outcomes

Change in glucose rate of appearance

Comparing glucose rate of appearance during exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in glucose rate of disappearance

Comparing glucose rate of disappearance during exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in glucose concentration

Comparing glucose concentration during exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in glucose enrichment in intramuscular glycogen

Comparing glucose enrichment in intramuscular glycogen during rest, exercise and recovery in the two groups

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in intramuscular glucose concentration

Comparing intramuscular glucose concentration during rest, exercise and recovery in the two groups

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in glycogen fractional synthesis rate

Comparing intramuscular glycogen fractional synthesis rate during rest, exercise and recovery in the two groups

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in gylcerol rate of appearance

Comparing gylcerol rate of appearance during rest, exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in gylcerol rate of disappearance

Comparing gylcerol rate of disappearance during rest, exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in gylcerol concentration

Comparing gylcerol concentration during rest, exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in palmitate rate of appearance

Comparing palmitate rate of appearance during rest, exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in palmitate rate of disappearance

Comparing palmitate rate of disappearance during rest, exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in palmitate concentration

Comparing palmitate kinetics during rest, exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in palmitate oxidation

Comparing palmitate oxidation during rest, exercise and recovery in the two groups

Time frame: Measured at -150, -60, -45, -30, 10, 30, 60, 90, 120, 130, 150, 180, 210, 240, 300 and 360 minutes

Change in intramuscular palmitate content

Comparing intramuscular palmitate content during rest, exercise and recovery in the two groups

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in palmitate enrichment in intramuscular triglycerides

Comparing palmitate enrichment in intramuscular triglycerides during rest, exercise and recovery in the two groups

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in intramuscular triglycerides fractional synthesis rate

Comparing intramuscular triglycerides fractional synthesis rate during rest, exercise and recovery in the two groups

Time frame: Measured at 0, 120, 180 and 360 minutes

Change in haemoglobin

Comparing haemoglobin during rest, exercise and recovery in the two groups