Cited by 295Exercise and Physiological ResponsesAdipokines, Inflammation, and Metabolic DiseasesCytokine Signaling Pathways and Interactions

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Interleukin 6 as an energy allocator in muscle tissue

Kistner, Timothy M., Pedersen, Bente K., Lieberman, Daniel E.·2022·Nature Metabolism

DOI 10.1038/s42255-022-00538-4

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Abstract

Extensive research has shown that interleukin 6 (IL-6) is a multifunctional molecule that is both proinflammatory and anti-inflammatory, depending on the context. Here, we combine an evolutionary perspective with physiological data to propose that IL-6's context-dependent effects on metabolism reflect its adaptive role for short-term energy allocation. This energy-allocation role is especially salient during physical activity, when skeletal muscle releases large amounts of IL-6. We predict that during bouts of physical activity, myokine IL-6 fulfills the three main characteristics of a short-term energy allocator: it is secreted from muscle in response to an energy deficit, it liberates somatic energy through lipolysis and it enhances muscular energy uptake and transiently downregulates immune function. We then extend this model of energy allocation beyond myokine IL-6 to reinterpret the roles that IL-6 plays in chronic inflammation, as well as during COVID-19-associated hyperinflammation and multiorgan failure.

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‘Small Changes' to Diet and Physical Activity Behaviors for Weight Management
Hills, A. P., Byrne, N. M., Lindstrom, R. C., & Hill, J. O. (2013) · Obesity Facts · doi:10.1159/000345030 · Cited by 9,526
Inflammation and metabolic disorders
Hotamisligil, G. S. (2006) · Nature · doi:10.1038/nature05485 · Cited by 9,199
Physical Activity in the United States Measured by Accelerometer
TROIANO, R. P., BERRIGAN, D., DODD, K. W., MÂSSE, L. C., TILERT, T., & MCDOWELL, M. (2008) · Medicine & Science in Sports & Exercise · doi:10.1249/mss.0b013e31815a51b3 · Cited by 7,638
How do glucocorticoids influence stress responses? Integrating permissive, suppressive, stimulatory, and preparative actions
Sapolsky, R. M., Romero, L. M., & Munck, A. U. (2000) · Endocrine Reviews · doi:10.1210/edrv.21.1.0389 · Cited by 7,541
In situ click chemistry generation of cyclooxygenase-2 inhibitors
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IL‐6 in inflammation, immunity, and disease
Tanaka, T., Narazaki, M., & Kishimoto, T. (2014) · Cold Spring Harbor Perspectives in Biology · doi:10.1101/cshperspect.a016295 · Cited by 5,046
The pro- and anti-inflammatory properties of the cytokine interleukin-6
Scheller, J., Chalaris, A., Schmidt-Arras, D., & Rose-John, S. (2011) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2011.01.034 · Cited by 3,212
The anti-inflammatory effect of exercise
Petersen, A. M. W., & Pedersen, B. K. (2005) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00164.2004 · Cited by 3,100
Muscle as an Endocrine Organ: Focus on Muscle-Derived Interleukin-6
Pedersen, B. K., & Febbraio, M. A. (2008) · Physiological Reviews · doi:10.1152/physrev.90100.2007 · Cited by 2,388
Endurance running and the evolution of Homo
Bramble, D. M., & Lieberman, D. E. (2004) · Nature · doi:10.1038/nature03052 · Cited by 1,748

Show all 149 references

Research works printed but not linked: 2

Stearns, S. C. The Evolution of Life Histories (Oxford University Press, 1992).
Bertholdt, L., Gudiksen, A., Schwartz, C. L., Knudsen, J. G. & Pilegaard, H. Lack of skeletal muscle IL-6 influences hepatic glucose metabolism in mice during prolonged exercise. Am. J. Physiol. 312, R626–R636 (2017).

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Yuan, C., Wang, S., Gebeyew, K., Yang, X., Tang, S., Zhou, C., Khan, N. A., Tan, Z., & Liu, Y. (2023) · Frontiers in Veterinary Science · doi:10.3389/fvets.2022.1098651 · Cited by 18
The immune-enhancing activity of egg white ovalbumin hydrolysate prepared with papain via MAPK signaling pathway in RAW 264.7 macrophages
Cho, H. Y., Lee, J., Lee, J. H., Ahn, D. U., & Paik, H. (2023) · Journal of Functional Foods · doi:10.1016/j.jff.2023.105487 · Cited by 17
Resource allocation in mammalian systems
Baghdassarian, H. M., & Lewis, N. E. (2024) · Biotechnology Advances · doi:10.1016/j.biotechadv.2023.108305 · Cited by 17
A nationwide study on immunosenescence biomarkers profile in older adults: ELSI-Brazil
Lima-Silva, M. L., Torres, K., Mambrini, J. V. D. M., Brot, N. C., Santos, S. O., Martins‐Filho, O. A., Teixeira‐Carvalho, A., Lima‐Costa, M. F., & Peixoto, S. V. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112433 · Cited by 17
“* Significant association (p < 0.05). its role as anti-inflammatory cytokine, particularly in muscle tissues, this cytokine has the most strengthen association with age, as documented in the Inflammaging process (Kistner et al., 2022; Pedersen and Febbraio, 2008).”
BackgroundInfluential
Stimulated myotube contractions regulate membrane-bound and soluble TLR4 to prevent LPS-induced signaling and myotube atrophy in skeletal muscle cells
Ducharme, J. B., Fennel, Z. J., McKenna, Z. J., Nava, R. C., & Deyhle, M. R. (2023) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.00007.2023 · Cited by 16
Different roles of circulating and intramuscular GDF15 as markers of skeletal muscle health
Chiariello, A., Conte, G., Rossetti, L. M., Trofarello, L., Salvioli, S., & Conte, M. (2024) · Frontiers in Endocrinology · doi:10.3389/fendo.2024.1404047 · Cited by 17
“Unfortunately, we do not have data on muscle-speci ﬁ c expression of IL6, however, being IL6 a well-known myokine needed to induce muscle repair (53, 54), it can be inferred that, in absence of overt infections, the large majority of circulating IL6 comes from muscles.”
Background
Effects of High-Intensity Functional Training (HIFT) on the Functional Capacity, Frailty, and Physical Condition of Older Adults with Mild Cognitive Impairment: A Blind Randomized Controlled Clinical Trial
Rivas-Campo, Y., Aibar‐Almazán, A., Afanador-Restrepo, D. F., García-Garro, P. A., Vega-Ávila, G. C., Rodríguez-López, C., Castellote‐Caballero, Y., Carcelén‐Fraile, M. D. C., & Lerma, L. L. (2023) · Life · doi:10.3390/life13051224 · Cited by 15
Revisiting Skeletal Muscle Dysfunction and Exercise in Chronic Obstructive Pulmonary Disease: Emerging Significance of Myokines
Han, L., Li, P., He, Q., Yang, C. G., Jiang, M., Wang, Y., Cao, Y., Han, X., Liu, X., & Wu, W. (2023) · Aging and Disease · doi:10.14336/ad.2023.1125 · Cited by 17
Metabolic liability for weight gain in early adulthood
Murthy, V. L., Mosley, J. D., Perry, A., Jacobs, D. R., Tanrıverdi, K., Zhao, S., Sawicki, K. T., Carnethon, M. R., Wilkins, J. T., Nayor, M. G., et al. (2024) · Cell Reports Medicine · doi:10.1016/j.xcrm.2024.101548 · Cited by 14
Il-6 signaling exacerbates hallmarks of chronic tendon disease by stimulating reparative fibroblastsPreprint
Stauber, T., Moschini, G., Hussien, A. A., Jaeger, P. K., Bock, K. D., & Snedeker, J. G. (2023) · eLife · doi:10.7554/elife.87092 · Cited by 15
Exerkines and myokines in aging sarcopenia
Wang, H., He, W., Chen, P., Wang, H., Wang, H., Zhu, L., & Liu, X. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1592491 · Cited by 20
AMPK Activation as a Protective Mechanism to Restrain Oxidative Stress in the Insulin-Resistant State in Skeletal Muscle of Rat Model of PCOS Subjected to Postnatal Overfeeding
Mićić, B., Djordjevic, A. D., Veličković, N. A., Kovačević, S., Martić, T., Μacut, D., & Milutinović, D. V. (2023) · Biomedicines · doi:10.3390/biomedicines11061586 · Cited by 14
“treatment are increased cytokines in these animals, since Il1b, as obesity-related, and Il6, as a muscle energy sensor, contribute to increased AMPK activity [51,52].”
Background
Impact of exercise on immune cell infiltration in muscle tissue: implications for muscle repair and chronic disease
Su, Y., & Su, Z. (2025) · Clinical and Experimental Medicine · doi:10.1007/s10238-025-01852-3 · Cited by 13
Hormonal, immune, and oxidative stress responses to blood flow‐restricted exercise
Hjortshoej, M. H., Aagaard, P., Storgaard, C. D., Juneja, H., Lundbye‐Jensen, J., Magnusson, S. P., & Couppé, C. (2023) · Acta Physiologica · doi:10.1111/apha.14030 · Cited by 13
Exercise, autoimmune diseases and T-regulatory cells
Blank, M., Israeli, D., & Shoenfeld, Y. (2024) · Journal of Autoimmunity · doi:10.1016/j.jaut.2024.103317 · Cited by 14
Myokines as potential mediators of changes in glucose homeostasis and muscle mass after bariatric surgery
Orioli, L., & Thissen, J. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1554617 · Cited by 17
“However, this effect appears to be restricted to speci ﬁ c muscle tissues (153).”
Inhibition of basal IL-6 activity promotes subcutaneous fat retention in humans during fasting and postprandial states
Trinh, B., Rasmussen, S. J., Brøgger-Jensen, M. E., Engelhard, C. A., Lund, A., Tavanez, A. R., Vassilieva, A., Janum, S., Iepsen, U. W., Kiens, B., et al. (2025) · Cell Reports Medicine · doi:10.1016/j.xcrm.2025.102042 · Cited by 17
“15 Whether IL-6 also plays a role in directing glucose to speciﬁc tissues or cells in the postprandial state remains unknown.”
Train your T cells: How skeletal muscles and T cells keep each other fit during aging
Slaets, H., Fonteyn, L., Eijnde, B. O., & Hellings, N. (2023) · Brain Behavior and Immunity · doi:10.1016/j.bbi.2023.03.006 · Cited by 12
IL-6 deletion decreased REV-ERBα protein and influenced autophagy and mitochondrial markers in the skeletal muscle after acute exercise
Pinto, A. P., Muñoz, V. R., da Rocha, A. L., Rovina, R. L., Ferrari, G. D., Alberici, L. C., Simabuco, F. M., Teixeira, G. R., Pauli, J. R., de Moura, L. P., et al. (2022) · Frontiers in Immunology · doi:10.3389/fimmu.2022.953272 · Cited by 14
“Interleukin 6 (IL-6) is a pleiotropic cytokine with roles in acute-phase response, skeletal mass, and metabolism (1).”
BackgroundResultInfluential
Prevalence of adiposity-based chronic disease and its association with anthropometric and clinical indices: a cross-sectional study
González-Salazar, L. E., Serralde-Zúñiga, A. E., Flores‐López, A., Díaz-Sánchez, J. P., Vera, I., Pichardo‐Ontiveros, E., Guizar-Heredia, R., Hernández-Gómez, K. G., Vigil‐Martínez, A., Arteaga-Sánchez, L., et al. (2022) · British Journal Of Nutrition · doi:10.1017/s0007114522002963 · Cited by 12
“…could regulate glucose production in the liver, lipolysis in adipose tissue and insulin secretion and can intramuscularly promote glucose uptake and fat oxidation through phosphoinositide 3-kinase (PI3K) activated by AMP-activated protein kinase (AMPK), thus improving insulin sensitivity (35) .”
Exercise as a therapeutic intervention for long-lasting and chronic diseases
Febbraio, M. A., & Pedersen, B. K. (2026) · Cell Metabolism · doi:10.1016/j.cmet.2026.02.017 · Cited by 12
Lipid-Independent Regulation of PLIN5 via IL-6 through the JAK/STAT3 Axis in Hep3B Cells
Krizanac, M., Sanchez, P. B. M., Schröder, S. K., Weiskirchen, R., & Asimakopoulos, A. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms24087219 · Cited by 11
“This was expected based on previous reports on IL-6 responsiveness in other cell types and tissues [23,44].”
Method
The potential protective effects of pre-injury exercise on neuroimmune responses following experimentally-induced traumatic neuropathy: a systematic review with meta-analysis
Koop, M. A., Sleijser‐Koehorst, M. L. S., Hooijmans, C. R., Tdlohreg, P. Q., Schipholt, I. J. L., Scholten-Peeters, G. G. M., & Coppieters, M. W. (2023) · Frontiers in Immunology · doi:10.3389/fimmu.2023.1215566 · Cited by 11
“Together with increased sympathoadrenal activity these responses induce an anti-inflammatory environment with each bout of exercise (22, 25, 26).”
Background
The effect of a combined lifestyle intervention with and without protein drink on inflammation in older adults with obesity and type 2 diabetes
Memelink, R. G., Njemini, R., Kuil, M. J. J. D. B., Wopereis, S., den Bosch, J. D. V., Schoufour, J. D., Tieland, M., Weijs, P. J. M., & Bautmans, I. (2024) · Experimental Gerontology · doi:10.1016/j.exger.2024.112410 · Cited by 13
“Next to its role as exercise signalling molecule, the myokine IL-6 also acts as a short-term energy allocator (Kistner et al., 2022).”
Background
The Influence of Nutrition Intervention on the P1NP and CTX-1 Response to an Acute Exercise Bout: A Systematic Review with Meta-Analysis
Dolan, E., Dumas, A., Esteves, G. P., Takarabe, L. L., Perfeito, L. A. M., Keane, K. M., Gualano, B., Kelley, G. A., Burke, L. M., Sale, C., et al. (2024) · Sports Medicine · doi:10.1007/s40279-024-02087-0 · Cited by 15
“…as a short-term energy allocator, which may have a role both in sensing the energy status of active muscle, including the rate of glycogen depletion, and in responding to energetic stress by liberating stored somatic energy and driving short-term energy allocation toward the active muscle [60].”
Bridging the tumor microenvironment: the pivotal role of cancer-associated fibroblasts in tumor cachexia development
Chen, G., Chen, B., Wu, Y., Nie, H., Zhong, Z., Yang, S., Qin, R., Kang, W., Zhang, C., Wang, N., et al. (2025) · Molecular Cancer · doi:10.1186/s12943-025-02379-7 · Cited by 15
“Conversely, IL-6 produced by tumor cells enhances inflammation and promotes tumor development [116].”
The 40-min HIIT acutely induced bone formation which was likely through the increases in muscle derived interleukin 6 and adiponectin activation: The 16 weeks of HIIT intervention, longitudinal randomized controlled trial
Sasimontonkul, S., & Sirivarasai, J. (2024) · Bone · doi:10.1016/j.bone.2024.117105 · Cited by 10
Mechanisms Underlying the Rarity of Skeletal Muscle Cancers
Kump, D. S. (2024) · International Journal of Molecular Sciences · doi:10.3390/ijms25126480 · Cited by 10
“SKM is a primary source of exercise-induced increases in IL-6, although it has a short clearance rate [209].”
Background
Nanoconfinement-guided in situ co-deposition of single-atom cascade nanozymes combined with injectable sodium alginate hydrogels for enhanced diabetic wound healing
Lan, F., Xin, T., Zhang, Y., Li, A., Wan, L., Du, J., Zheng, P., Nie, C., Pan, Q., & Zhu, W. (2025) · International Journal of Biological Macromolecules · doi:10.1016/j.ijbiomac.2025.140814 · Cited by 11
Weight Loss‐Associated Remodeling of Adipose Tissue Immunometabolism
Basso, P. J., Schcolnik‐Cabrera, A., Zhu, M., Strachan, E. R., Clemente‐Casares, X., & Tsai, S. J. (2025) · Obesity Reviews · doi:10.1111/obr.13975 · Cited by 13
“In individuals with obesity engaging in exercise, skeletal muscle-released IL-6 induces VAT lipolysis and therefore diminishes VAT mass [181], an effect that allows AT-derived FAs to shunt toward the exercising muscles [182] while simultaneously reducing pro-inflammatory ATMs [180].”
Dynamic IL-6R/STAT3 signaling leads to heterogeneity of metabolic phenotype in pancreatic ductal adenocarcinoma cells
Blaszczak, W., White, B., Monterisi, S., & Swietach, P. (2024) · Cell Reports · doi:10.1016/j.celrep.2023.113612 · Cited by 9
The role of O3 exposure and physical activity status on redox state, inflammation, and pulmonary toxicity of young men: A cross-sectional study
Marmett, B., Carvalho, R. B., da Silva, G. N., Dorneles, G. P., Romão, P. R. T., Nunes, R. B., & Rhoden, C. R. (2023) · Environmental Research · doi:10.1016/j.envres.2023.116020 · Cited by 10
Intervention points for the role of physical activity in prevention and treatment of Alzheimer's disease
Brendborg, N., & Febbraio, M. A. (2025) · The Journal of Physiology · doi:10.1113/jp286747 · Cited by 10
Integrating Graphene Oxide and Mesenchymal Stem Cells in 3D-Printed Systems for Drug Delivery and Tissue Regeneration
Grecca, I. S. G., Miola, V. F. B., Ferreira, J. C., Rissato, T., da Silva, L. M. D., Totti, P. G. F., Gianini, S. H. S., de Souza, M. D. S. S., de Souza, J. D. S. S., Araújo, A. C., et al. (2025) · Pharmaceutics · doi:10.3390/pharmaceutics17081088 · Cited by 9
“Epidermal growth factor (EGF) stimulates cell proliferation and differentiation and participates in tissue repair and wound healing [35].”
Interleukin 6 receptor is not directly involved in regulation of body weight in diet-induced obesity with and without physical exercise
Minafra, A. R., Chadt, A., Rafii, P., Al‐Hasani, H., Behnke, K., & Scheller, J. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.1028808 · Cited by 9
“IL-6 signalling has been reported to be involved not only in regulation of weight loss but also in improved glucose and insulin sensitivity induced by physical activity (14).”
Background
Characteristics of the Protocols Used in Electrical Pulse Stimulation of Cultured Cells for Mimicking In Vivo Exercise: A Systematic Review, Meta-Analysis, and Meta-Regression
Nintou, E., Karligiotou, E., Vliora, M., Ioannou, L. G., & Flouris, A. D. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232113446 · Cited by 9
“It plays key anti-diabetic roles, enhancing muscular glucose uptake, exerting effects on pancreatic insulin secretion, and promoting fatty-acid oxidation and lipolysis [75].”
Background

Authors: Kistner, T. M., Pedersen, B. K., & Lieberman, D. E.
Affiliations: Harvard University (US)
University of Copenhagen (DK)
Corresponding author: Kistner, Timothy M.
Pedersen, Bente K.
Lieberman, Daniel E.
ORCID: Kistner, Timothy M.
Pedersen, Bente K.
Lieberman, Daniel E.
Venue: Nature Metabolism
Publisher: Springer Science and Business Media LLC
Published: 2022-02-24
Volume: 4
Issue: 2
Pages: 170-179
ISSN: 2522-5812 (ISSN-L)
DOI: 10.1038/s42255-022-00538-4
OpenAlex: W4213414654
Cited by: 295
References: 149
Citations by year: 2026: 54 · 2025: 87 · 2024: 68 · 2023: 56 · 2022: 30
FWCI: 7.14
Type: journal article
Language: en
Open access: closed
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Nature Metabolism (publishedVersion)
PubMed (publishedVersion)
Research at the University of Copenhagen (University of Copenhagen) (publishedVersion)
Topics: Health Sciences › Medicine › Physiology (medical) › Exercise and Physiological Responses
Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adipokines, Inflammation, and Metabolic Diseases
Life Sciences › Immunology and Microbiology › Immunology › Cytokine Signaling Pathways and Interactions
Keywords: interleukin-6, myokines, energy allocation, skeletal muscle, physical activity, lipolysis, energy metabolism, chronic inflammation, multiple organ failure, evolutionary perspective
MeSH terms: COVID-19, SARS-CoV-2, Humans, Exercise, Interleukin-6, Muscle, Skeletal

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Interleukin 6 as an energy allocator in muscle tissue

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