TNF-α impairs regulation of muscle oxidative phenotype: implications for cachexia?
Open accessAbstract
ABSTRACT Chronic obstructive pulmonary disease (COPD) is characterized by weight loss, muscle wasting (in advanced disease ultimately resulting in cachexia), and loss of muscle oxidative phenotype (oxphen). This study investigates the effect of inflammation (as a determinant of muscle wasting) on muscle oxphen by using cell studies combined with analyses of muscle biopsies of patients with COPD and control participants. We analyzed markers ( citrate synthase, fi‐hydroxya‐cyl‐CoA dehydrogenase, and cytochrome c oxidase IV ) and regulators ( PGC‐1α, PPAR‐α, and Tfam ) of oxphen in vastus lateralis muscle biopsies of patients with advanced COPD and healthy smoking control participants. Here 17 of 73 patients exhibited elevated muscle TNF‐α mRNA levels. In these patients, significantly lower mRNA levels of all oxidative markers/regulators were found. Interestingly, these patients also had a significantly lower body mass index and tended to have less muscle mass. In cultured muscle cells, mitochon‐drial protein content and myosin heavy chain isoform I (but not II) protein and mRNA levels were reduced on chronic TNF‐α stimulation. TNF‐α also reduced mito‐chondrial respiration in a nuclear factor kappaB (NF‐κB ) ‐dependent manner. Importantly, TNF‐α‐induced NF‐κB activation decreased promoter transactivation and transcriptional activity of regulators of mitochon‐drial biogenesis and muscle oxphen. In conclusion, these results demonstrate that TNF‐α impairs muscle oxphen in a NF‐κB‐dependent manner.—Remels, A. H. V., Gosker, H. R., Schrauwen, P., Hommelberg, P. P. H., Sliwinski, P., Polkey, M., Galdiz, J., Wouters, E. F. M., Langen, R. C. J., Schols, A. M. W. J. TNF‐α impairs regulation of muscle oxidative phenotype: implications for cachexia? FASEBJ. 24, 5052–5062 (2010). www.fasebj.org
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In the quadriceps of COPD patients, muscular TNF-α levels have been reported as significantly elevated, decreased, and unaltered, or even undetected at the protein level.
“with regards to muscular TNF-α, significantly elevated, decreased, and unaltered levels have been reported in the quadriceps of COPD patients [27,28,29], or even undetected at the protein level [30,31]”
From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [31]
The retrieved copy contains the paper’s title and bibliographic material (section labeled Abstract, no page), but no passage about quadriceps TNF-α levels in COPD patients. Searches for elevated, decreased, unaltered, and undetected muscle TNF-α did not find evidence to assess the claim. (LLM, conf=0.70)
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Cites
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- Authors
- Remels, A. H. V., Gosker, H. R., Schrauwen, P., Hommelberg, P. P. H., Sliwinski, P., Polkey, M., Galdiz, J., Wouters, E. F. M., Langen, R. C. J., & Schols, A. M. W. J.
- Affiliations
- Maastricht University Medical Centre (NL)
- Department of Respiratory Medicine, Institute of Tuberculosis and Lung Diseases, Warsaw, Poland;
- Royal Brompton Hospital (GB)
- Pneumology Department and Research Unit, Cruces Hospital, Basque Country University, Barakaldo, Spain; and
- Venue
- The FASEB Journal
- Publisher
- Wiley
- Published
- 2010-12
- Volume
- 24
- Issue
- 12
- Pages
- 5052-5062
- ISSN
- 0892-6638 (ISSN-L)
- 1530-6860
- OpenAlex
- W2054261345
- Cited by
- 122
- References
- 6
- Citations by year
- 2026: 1 · 2025: 3 · 2024: 1 · 2023: 4 · 2022: 8 · 2021: 3 · 2020: 8 · 2019: 6 · 2018: 5 · 2017: 10 · 2016: 9 · 2015: 14 · 2014: 15 · 2013: 17 · 2012: 10
- FWCI
- 4.56
- Type
- journal article
- Language
- en
- Open access
- Licence
- other-oa
- Locations
- The FASEB Journal (publishedVersion)
- PubMed (publishedVersion)
- Research Publications (Maastricht University) (publishedVersion, other-oa)
- Research Publications (Maastricht University) (submittedVersion, other-oa)
- Funders
- Koninklijke Nederlandse Akademie van Wetenschappen
- Asthma Foundation ACT (NAF 3.2.08.061)
- 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 › Physiology › Adipose Tissue and Metabolism
- Keywords
- TNF-α, chronic obstructive pulmonary disease, cachexia, muscle atrophy, mitochondrial biogenesis, NF-κB, PGC-1α, PPARα, TFAM, myosin heavy chain isoforms, mitochondrial respiration, inflammation, vastus lateralis
- MeSH terms
- Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Animals, Cachexia, Cell Line, Citrate (si)-Synthase, Electron Transport Complex IV, DNA-Binding Proteins, Enzyme-Linked Immunosorbent Assay, Heat-Shock Proteins, Humans, Hydro-Lyases, Transcription Factors, Tumor Necrosis Factor-alpha, Blotting, Western, NF-kappa B, Muscle, Skeletal, Mitochondrial Proteins, Electrophoretic Mobility Shift Assay, Pulmonary Disease, Chronic Obstructive, PPAR alpha, Mice
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