Aim: Exercise training improves the risk of cardiometabolic diseases; yet the underlying
mechanisms are unclear. Exercise induces release of IL-6 from skeletal muscle. Acute
elevations in IL-6 improve lipid and glucose metabolism, the latter partly through a delayed
gastric emptying. Physical inactivity causes accumulation of visceral fat (VAT). Visceral and
epicardial adipose tissue (EAT) is more inflamed than subcutaneous adipose tissue. Thus, the
investigators hypothesize that exercise-induced IL-6 mediates the exercise-induced reduction
in EAT and VAT. Secondly, the investigators hypothesize that exercise-induced adaptations in
glucose metabolism and gastric motility are dependent on IL-6. Finally the investigators
hypothesise that both endurance and resistance exercise training reduce VAT and EAT.
Primary aim: To investigate the effects of exercise training on VAT and to determine to what
extend IL-6 mediates this effect.
Secondary aims: 1) To determine whether 12 weeks of endurance and strength training can
reduce the amount of EAT. 2) To study whether the effects of exercise on glucose metabolism
and gastric emptying are dependent on IL-6.
Methods: Inclusion: 70 inactive men and women, >18 years, waist to height ratio > 0.5 and/or
waist circumference ≥ 88 cm (women); waist circumference ≥ 102 cm (men) Design: A 12-week,
double-blinded randomised, placebo-controlled exercise intervention study.
Intervention: Subjects will be randomised to one of five groups: i) Tocilizumab (IL-6
receptor antibody) and endurance training, ii) Placebo to Tocilizumab and endurance training,
iii) Tocilizumab, no exercise iv) Placebo to Tocilizumab and no training, and v) Placebo to
Tocilizumab, and resistance training. Tocilizumab/placebo dose will be administered
(according to standard recommendations) before the first training session, and maintained
during the 12-week training program. Training will be supervised to ensure intensity and
compliance. Subjects will be instructed not to change eating habits and informed that this
study does not aim for a weight loss.
Statistical considerations: Study investigators are blinded to treatment allocation. Dropouts
will be replaced. A sample size of 70 subjects is needed to detect a 10% change in visceral
adipose, with a power of 80% and a significance level of 0.05.