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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See all 295

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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