Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial

Anne-Sophie Wedell-Neergaard, Louise Lang Lehrskov, Regitse Højgaard Christensen, Grit Elster Legaard, Emma Dorph, Monica Korsager Larsen, Natja Launbo, Sabrina Ravn Fagerlind, Sidsel Kofoed Seide, Stine Nymand, Maria Ball, Nicole Vinum, Camilla Noerfelt Dahl, Marie Henneberg, Mathias Ried-Larsen, Janus Damm Nybing, Robin Christensen, Jaya Birgitte Rosenmeier, Kristian Karstoft, Bente Klarlund PedersenHelga Ellingsgaard*, Rikke Krogh-Madsen

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review


Visceral adipose tissue is harmful to metabolic health. Exercise training reduces visceral adipose tissue mass, but the underlying mechanisms are not known. Interleukin-6 (IL-6) stimulates lipolysis and is released from skeletal muscle during exercise. We hypothesized that exercise-induced reductions in visceral adipose tissue mass are mediated by IL-6. In this randomized placebo-controlled trial, we assigned abdominally obese adults to tocilizumab (IL-6 receptor antibody) or placebo during a 12-week intervention with either bicycle exercise or no exercise. While exercise reduced visceral adipose tissue mass, this effect of exercise was abolished in the presence of IL-6 blockade. Changes in body weight and total adipose tissue mass showed similar tendencies, whereas lean body mass did not differ between groups. Also, IL-6 blockade increased cholesterol levels, an effect not reversed by exercise. Thus, IL-6 is required for exercise to reduce visceral adipose tissue mass and emphasizes a potentially important metabolic consequence of IL-6 blockade. Wedell-Neergaard et al. show that in abdominally obese people, exercise-mediated loss of visceral adipose tissue mass requires IL-6 receptor signaling. Given that abdominal fat is metabolically harmful to health, this study raises a potentially important side effect of IL-6 receptor antibodies, such as tocilizumab, used to treat some forms of arthritis.

Original languageEnglish
JournalCell Metabolism
Issue number4
Pages (from-to)844-855.e3
Publication statusPublished - 2. Apr 2019


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