Aerobic Exercise Induces Cardiac Fat Loss and Alters Cardiac Muscle Mass Through an Interleukin-6 Receptor–Dependent Mechanism: Cardiac Analysis of a Double-Blind Randomized Controlled Clinical Trial in Abdominally Obese Humans
Abstract
HomeCirculationVol. 140, No. 20Aerobic Exercise Induces Cardiac Fat Loss and Alters Cardiac Muscle Mass Through an Interleukin-6 Receptor–Dependent Mechanism Free AccessLetterPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessLetterPDF/EPUBAerobic Exercise Induces Cardiac Fat Loss and Alters Cardiac Muscle Mass Through an Interleukin-6 Receptor–Dependent MechanismCardiac Analysis of a Double-Blind Randomized Controlled Clinical Trial in Abdominally Obese Humans Regitse Højgaard Christensen, MD, PhD, Louise Lang Lehrskov, MD, PhD, Anne-Sophie Wedell-Neergaard, MD, PhD, Grit Elster Legaard, MD, Mathias Ried-Larsen, PhD, Kristian Karstoft, MD, PhD, Rikke Krogh-Madsen, MD, PhD, Bente Klarlund Pedersen, MD, DMSc, Helga Ellingsgaard, PhD and Jaya Birgitte Rosenmeier, MD, PhD Regitse Højgaard ChristensenRegitse Højgaard Christensen Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Louise Lang LehrskovLouise Lang Lehrskov Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Anne-Sophie Wedell-NeergaardAnne-Sophie Wedell-Neergaard Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Grit Elster LegaardGrit Elster Legaard Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Mathias Ried-LarsenMathias Ried-Larsen Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Kristian KarstoftKristian Karstoft Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Rikke Krogh-MadsenRikke Krogh-Madsen Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Bente Klarlund PedersenBente Klarlund Pedersen Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). , Helga EllingsgaardHelga Ellingsgaard Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.). and Jaya Birgitte RosenmeierJaya Birgitte Rosenmeier Jaya Birgitte Rosenmeier, MD, PhD, Department of Cardiology, Copenhagen University Hospital Bispebjerg, Copenhagen, Denmark. Email E-mail Address: [email protected] Department of Cardiology, Copenhagen University Hospital Bispebjerg, Denmark (J.B.R.). Originally published11 Nov 2019https://doi.org/10.1161/CIRCULATIONAHA.119.042287Circulation. 2019;140:1684–1686Epicardial and pericardial adipose tissues (EAT and PAT) are cardiac fat depots and independent risk factors of cardiovascular disease. Exercise training reduces EAT and PAT1 through lipolysis, which is partially induced by acute discharge of adrenaline2 and interleukin-6 (IL-6).3 IL-6 has been shown to stimulate myocardial hypertrophy in vitro and in vivo,4 but it is not known whether IL-6 regulates exercise-induced adaptations in cardiac fat and left myocardial mass (LVM) in humans. Thus, the present study aimed to test whether aerobic exercise training reduces cardiac fat through an IL-6 receptor–dependent mechanism and moreover to investigate the role of IL-6 signaling in training-induced adaptations of the myocardium.This study presents the preplanned secondary analysis of a larger single-center, double-blind, randomized exercise intervention study. The methods for this study have been described previously.1,5 In short, the final study population comprised 52 abdominally obese but otherwise healthy participants randomly assigned to moderate/high-intensity aerobic exercise (3 sessions of 45 minutes per week reaching 70%–85% of Vo2max) or no exercise with or without monthly infusions of the IL-6 receptor antagonist tocilizumab (RoActemra, Roche Pharma AG) in the clinical standard dose of 8 mg/kg or saline (placebo; Figure, A).Download figureDownload P
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Exercise training leads to a decrease in visceral and cardiac fat mass and hence a decrease in circulating inflammatory molecules via a mechanism that involves exercise-induced increase in IL-6.
“Exercise training will lead to a decrease in visceral and cardiac fat mass (136, 138, 221) and hence a decrease in circulating inflammatory molecules via a mechanism that involves exercise-induced increase in IL-6 (136), as described above.”
From Muscle–Organ Crosstalk: The Emerging Roles of Myokines (2020) · cites this paper as [138]
IL6 receptor signalling plays an important role in the reduction of cardiac-especially epicardial-fat depots and increases in LV mass with aerobic training.
“In addition, there is evidence for an important role of IL6 receptor signalling on the reduction of cardiac-especially epicardial-fat depots and increases in LV mass with aerobic training.182”
From Exercise benefits in cardiovascular diseases: From mechanisms to clinical implementation (2023) · cites this paper as [182]
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- Authors
- Christensen, R. H., Lehrskov, L. L., Wedell-Neergaard, A.-S., Legaard, G. E., Ried-Larsen, M., Karstoft, K., Krogh-Madsen, R., Pedersen, B. K., Ellingsgaard, H., & Rosenmeier, J. B.
- Affiliations
- University of Copenhagen (DK)
- Centre of Inflammation and Metabolism and the Centre for Physical Activity Research, Rigshospitalet, University of Copenhagen, Denmark (R.H.C., L.L.L., A.-S.W.-N., G.E.L., M.R.-L., K.K., R.K.-M., B.K.P., H.E.).
- Bispebjerg Hospital (DK)
- ORCID
- Venue
- Circulation
- Published
- 2019-11-12
- Volume
- 140
- Issue
- 20
- Pages
- 1684-1686
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2988354490
- Cited by
- 57
- References
- 5
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 11 · 2023: 7 · 2022: 6 · 2021: 6 · 2020: 8
- FWCI
- 3.61
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
- Funders
- Strategiske Forskningsråd (09-067009 and 09-075724, 09–067009, 09 – 075724)
- Hjerteforeningen (16‐R107‐A6704‐22970)
- Danish Diabetes Academy
- Novo Nordisk
- TrygFonden (16-R107-A6704-22970)
- Novo Nordisk Fonden
- Center for Strategic Research
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Disease and Adiposity
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac Fibrosis and Remodeling
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Effects of Exercise
- Keywords
- aerobic exercise, IL-6 receptor, IL-6 signaling, abdominal obesity, exercise training, cardiometabolic health, cardiomyocyte hypertrophy, cardiomyocyte atrophy, cardiomyocyte apoptosis, cardiomyocyte proliferation, cardiomyocyte fibrosis
- MeSH terms
- Adipose Tissue, Adult, Double-Blind Method, Exercise Therapy, Female, Humans, Male, Middle Aged, Myocardium, Time Factors, Signal Transduction, Treatment Outcome, Receptors, Interleukin-6, Adiposity, Obesity, Abdominal, Antibodies, Monoclonal, Humanized
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