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Cited by 213Muscle Physiology and DisordersNutrition and Health in AgingAdrenal Hormones and Disorders

Central nervous system inflammation induces muscle atrophy via activation of the hypothalamic–pituitary–adrenal axis

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Braun, Theodore P., Zhu, Xinxia, Szumowski, Marek, Scott, Gregory D., Grossberg, Aaron J., Levasseur, Peter R., Graham, Kathryn, Khan, Sheehan +4 more·2011·Journal of Experimental Medicine
DOI 10.1084/jem.20111020PMC PMC3256966
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Abstract

Skeletal muscle catabolism is a co-morbidity of many chronic diseases and is the result of systemic inflammation. Although direct inflammatory cytokine action on muscle promotes atrophy, nonmuscle sites of action for inflammatory mediators are less well described. We demonstrate that central nervous system (CNS)–delimited interleukin 1β (IL-1β) signaling alone can evoke a catabolic program in muscle, rapidly inducing atrophy. This effect is dependent on hypothalamic–pituitary–adrenal (HPA) axis activation, as CNS IL-1β–induced atrophy is abrogated by adrenalectomy. Furthermore, we identified a glucocorticoid-responsive gene expression pattern conserved in models of acute and chronic inflammatory muscle atrophy. In contrast with studies suggesting that the direct action of inflammatory cytokines on muscle is sufficient to induce catabolism, adrenalectomy also blocks the atrophy program in response to systemic inflammation, demonstrating that glucocorticoids are requisite for this process. Additionally, circulating levels of glucocorticoids equivalent to those produced under inflammatory conditions are sufficient to cause profound muscle wasting. Together, these data suggest that a significant component of inflammation-induced muscle catabolism occurs indirectly via a relay in the CNS.

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  • CNS inflammation activates the HPA axis, leading to muscle atrophy via catabolic pathways like ubiquitin-proteasome degradation.

    “Braun et al. showed that CNS inflammation activates the HPA axis, leading to muscle atrophy via catabolic pathways like ubiquitin-proteasome degradation [76].”

    From Chronic Stress and Autoimmunity: The Role of HPA Axis and Cortisol Dysregulation (2025) · cites this paper as [76]

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Authors
Braun, T. P., Zhu, X., Szumowski, M., Scott, G. D., Grossberg, A. J., Levasseur, P. R., Graham, K., Khan, S., Damaraju, S., Colmers, W. F., Baracos, V. E., & Marks, D. L.
Affiliations
  • Oregon Health & Science University (US)
  • University of Alberta (CA)
Corresponding author
Marks, Daniel L.
ORCID
Venue
Journal of Experimental Medicine
Publisher
Rockefeller University Press
Published
2011-11-14
Volume
208
Issue
12
Pages
2449-2463
ISSN
  • 0022-1007 (ISSN-L)
  • 1540-9538
DOI
10.1084/jem.20111020
PMC
PMC3256966
OpenAlex
W2139827430
Cited by
213
References
11
Citations by year
2026: 16 · 2025: 15 · 2024: 13 · 2023: 22 · 2022: 20 · 2021: 17 · 2020: 20 · 2019: 9 · 2018: 13 · 2017: 10 · 2016: 10 · 2015: 13 · 2014: 13 · 2013: 14 · 2012: 8
FWCI
4.55
Type
journal article
Language
en
Open access
Locations
  • The Journal of Experimental Medicine (publishedVersion)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
  • PubMed Central (publishedVersion, cc-by-nc-sa)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • Canadian Institutes of Health Research (200948)
  • National Heart, Lung, and Blood Institute (F30HL106930)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01DK070333, DK 084646, DK70333, F30DK084646)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
  • Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Adrenal Hormones and Disorders
Keywords
muscle atrophy, skeletal muscle catabolism, neuroinflammation, hypothalamic-pituitary-adrenal axis, IL-1β, glucocorticoids, adrenalectomy, systemic inflammation
MeSH terms
Adrenalectomy, Analysis of Variance, Animals, Central Nervous System, Corticosterone, Enzyme-Linked Immunosorbent Assay, Glucocorticoids, Humans, Hypothalamo-Hypophyseal System, Immunohistochemistry, Inflammation, Mice, Inbred C57BL, Muscular Atrophy, Pituitary-Adrenal System, Blotting, Western, Signal Transduction, Rats, Sprague-Dawley, In Situ Hybridization, Muscle, Skeletal, Gene Expression Profiling, Microarray Analysis, Mice, Rats, Interleukin-1beta, Real-Time Polymerase Chain Reaction

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