Differential Effects of Sepsis and Chronic Inflammation on Diaphragm Muscle Fiber Type, Thyroid Hormone Metabolism, and Mitochondrial Function
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BACKGROUND: The diaphragm is the main respiratory muscle, and its function is compromised during severe illness. Altered local thyroid hormone (TH) metabolism may be a determinant of impaired muscle function during illness. METHODS: This study investigates the effects of bacterial sepsis and chronic inflammation on muscle fiber type, local TH metabolism, and mitochondrial function in the diaphragm. Two mouse models were used: sepsis induced by S. pneumoniae infection or chronic inflammation induced by subcutaneous turpentine injection. In vitro, the effect of bacterial endotoxin (LPS) on mitochondrial function in C2C12 myotubes was studied. RESULTS: Sepsis induced a transient increase in the fiber type I profile and increased Dio3 expression while decreasing Dio2, Thra1, and Slc16a2 expression. Triiodothyronine positively regulated genes Tnni2 and Myog were decreased, indicating reduced TH signaling in the diaphragm. In contrast, chronic inflammation increased the fiber type II profile in the diaphragm as well as Thra1, Thrb1, and Myog expression while decreasing Dio3 expression, suggesting increased TH responsiveness during chronic inflammation. LPS-stimulated C2C12 myotubes showed decreased Dio2 expression and reduced basal oxygen consumption as well as non-mitochondrial respiration. The same respiratory profile was induced by Dio2 knockdown in myotubes. CONCLUSIONS: The in vivo results show differential effects of sepsis and chronic inflammation on diaphragm muscle fiber type, TH metabolism, and mitochondrial function, while the in vitro results point to a causal role for altered TH metabolism in functional muscle impairment. These findings may be relevant for the pathogenesis of impaired respiratory function in critical illness.
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In the same animal model, bacterial sepsis reduces TH signaling coinciding with increased DIO3 and decreased DIO2 expression, while chronic inflammation decreases DIO3 expression.
“In the same animal model, bacterial sepsis reduces TH signaling coinciding with increased DIO3 and decreased DIO2 expression, while chronic inflammation decreases DIO3 expression [48].”
From An update on non-thyroidal illness syndrome (2021) · cites this paper as [48]
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- Authors
- Bloise, F. F., van der Spek, A. H., Surovtseva, O. V., Ortiga-Carvalho, T. M., Fliers, E., & Boelen, A.
- Affiliations
- Department of Endocrinology and Metabolism, Academic Medical Centre, University of Amsterdam, Amsterdam, The Netherlands.
- Amsterdam UMC Location University of Amsterdam (NL)
- Institute of Biophysics Carlos Chagas Filho, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil.
- Venue
- Thyroid
- Publisher
- SAGE Publications
- Published
- 2016-04
- Volume
- 26
- Issue
- 4
- Pages
- 600-609
- ISSN
- 1050-7256 (ISSN-L)
- 1557-9077
- OpenAlex
- W2304555545
- Cited by
- 21
- References
- 27
- Citations by year
- 2024: 1 · 2022: 3 · 2021: 2 · 2020: 5 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 1
- FWCI
- 1.73
- Type
- journal article
- Language
- en
- Open access
- green
- pure.amsterdamumc.nl
- Locations
- Thyroid (publishedVersion)
- PubMed (publishedVersion)
- Pure Amsterdam UMC (submittedVersion, other-oa)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Funders
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Ciência sem Fronteiras
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Mitochondrial Function and Pathology
- Health Sciences › Medicine › Epidemiology › Sepsis Diagnosis and Treatment
- Keywords
- sepsis, chronic inflammation, diaphragm, muscle fiber type, thyroid hormone metabolism, mitochondrial function, DIO2, DIO3, endotoxin, respiratory muscle dysfunction, critical illness, turpentine
- MeSH terms
- Iodothyronine Deiodinase Type II, Animals, Female, Inflammation, Iodide Peroxidase, Mice, Inbred C57BL, Mitochondria, Muscles, Pneumococcal Infections, Respiratory Muscles, Thyroid Hormones, Time Factors, Myogenin, Sepsis, Troponin I, Membrane Transport Proteins, Monocarboxylic Acid Transporters, Symporters, Mice, Mediator Complex
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