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

• Published in: Cell metabolism Vol. 29; no. 4; pp. 844 - 855.e3
• Main Authors: Wedell-Neergaard, Anne-Sophie, Lang Lehrskov, Louise, Christensen, Regitse Højgaard, Legaard, Grit Elster, Dorph, Emma, Larsen, Monica Korsager, Launbo, Natja, Fagerlind, Sabrina Ravn, Seide, Sidsel Kofoed, Nymand, Stine, Ball, Maria, Vinum, Nicole, Dahl, Camilla Noerfelt, Henneberg, Marie, Ried-Larsen, Mathias, Nybing, Janus Damm, Christensen, Robin, Rosenmeier, Jaya Birgitte, Karstoft, Kristian, Pedersen, Bente Klarlund, Ellingsgaard, Helga, Krogh-Madsen, Rikke
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 02.04.2019
• ISSN: 1550-4131; 1932-7420; 1932-7420
• DOI: 10.1016/j.cmet.2018.12.007

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. [Display omitted] •Exercise reduces visceral adipose tissue mass•Loss of visceral adipose tissue mass following exercise is dependent on IL-6•IL-6 receptor blockade increases total cholesterol and is not influenced by exercise•Improvements in cardiorespiratory fitness following exercise are not IL-6 dependent 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.