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

Abstract

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
Volume29
Issue number4
Pages (from-to)844-855.e3
ISSN1550-4131
DOIs
Publication statusPublished - 2. Apr 2019

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Intra-Abdominal Fat
Interleukin-6
Randomized Controlled Trials
Exercise
Interleukin-6 Receptors
Placebos
Abdominal Fat
Health
Adipose Tissue
Skeletal Muscle

Cite this

Wedell-Neergaard, A-S., Lang Lehrskov, L., Christensen, R. H., Legaard, G. E., Dorph, E., Larsen, M. K., ... Krogh-Madsen, R. (2019). Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial. Cell Metabolism, 29(4), 844-855.e3. https://doi.org/10.1016/j.cmet.2018.12.007
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. / Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling : A Randomized Controlled Trial. In: Cell Metabolism. 2019 ; Vol. 29, No. 4. pp. 844-855.e3.
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title = "Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial",
abstract = "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.",
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Wedell-Neergaard, A-S, Lang Lehrskov, L, Christensen, RH, Legaard, GE, Dorph, E, Larsen, MK, Launbo, N, Fagerlind, SR, Seide, SK, Nymand, S, Ball, M, Vinum, N, Dahl, CN, Henneberg, M, Ried-Larsen, M, Nybing, JD, Christensen, R, Rosenmeier, JB, Karstoft, K, Pedersen, BK, Ellingsgaard, H & Krogh-Madsen, R 2019, 'Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial', Cell Metabolism, vol. 29, no. 4, pp. 844-855.e3. https://doi.org/10.1016/j.cmet.2018.12.007

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

In: Cell Metabolism, Vol. 29, No. 4, 02.04.2019, p. 844-855.e3.

Research output: Contribution to journalJournal articleResearchpeer-review

TY - JOUR

T1 - Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling

T2 - A Randomized Controlled Trial

AU - Wedell-Neergaard, Anne-Sophie

AU - Lang Lehrskov, Louise

AU - Christensen, Regitse Højgaard

AU - Legaard, Grit Elster

AU - Dorph, Emma

AU - Larsen, Monica Korsager

AU - Launbo, Natja

AU - Fagerlind, Sabrina Ravn

AU - Seide, Sidsel Kofoed

AU - Nymand, Stine

AU - Ball, Maria

AU - Vinum, Nicole

AU - Dahl, Camilla Noerfelt

AU - Henneberg, Marie

AU - Ried-Larsen, Mathias

AU - Nybing, Janus Damm

AU - Christensen, Robin

AU - Rosenmeier, Jaya Birgitte

AU - Karstoft, Kristian

AU - Pedersen, Bente Klarlund

AU - Ellingsgaard, Helga

AU - Krogh-Madsen, Rikke

N1 - Copyright © 2018 Elsevier Inc. All rights reserved.

PY - 2019/4/2

Y1 - 2019/4/2

N2 - 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.

AB - 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.

U2 - 10.1016/j.cmet.2018.12.007

DO - 10.1016/j.cmet.2018.12.007

M3 - Journal article

C2 - 30595477

VL - 29

SP - 844-855.e3

JO - Cell Metabolism

JF - Cell Metabolism

SN - 1550-4131

IS - 4

ER -

Wedell-Neergaard A-S, Lang Lehrskov L, Christensen RH, Legaard GE, Dorph E, Larsen MK et al. Exercise-Induced Changes in Visceral Adipose Tissue Mass Are Regulated by IL-6 Signaling: A Randomized Controlled Trial. Cell Metabolism. 2019 Apr 2;29(4):844-855.e3. https://doi.org/10.1016/j.cmet.2018.12.007