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Cited by 168Muscle Physiology and DisordersChronic Obstructive Pulmonary Disease (COPD) ResearchNutrition and Health in Aging

Peroxisome Proliferator-Activated Receptor Expression Is Reduced in Skeletal Muscle in COPD

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Remels, A. H., Schrauwen, P., Broekhuizen, R., Willems, J., Kersten, S., Gosker, H. R., Schols, A. M.·2007·European Respiratory Journal
DOI 10.1183/09031936.00144106
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Abstract

Chronic obstructive pulmonary disease (COPD) is a multiorgan systemic disease. The systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. The exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure. Recent evidence suggests involvement of the peroxisome proliferator-activated receptors (PPARs) and PPAR-γ coactivator (PGC)-1α in regulation of skeletal muscle morphology and metabolism, and mitochondrial transcription factor A (TFAM) has been implicated in the process of mitochondrial biogenesis. The aim of the present exploratory study was, therefore, to compare these factors in the skeletal muscle of nine healthy control subjects and 14 COPD patients stratified by cachexia. PPAR-γ, PPAR-δ and TFAM were measured at the mRNA and protein level by real-time quantitative PCR and Western blotting, respectively. PPAR-α and PGC-1α were meansured at the mRNA level. PPAR-δ and TFAM protein content, as well as PGC-1α mRNA levels, were decreased in the skeletal muscle of COPD patients compared with healthy controls. The cachectic COPD subgroup was further characterised by decreased PPAR-α mRNA expression and decreased TFAM protein and mRNA levels compared with noncachectic COPD patients. In addition, PPAR-α mRNA levels in skeletal muscle correlated negatively with inflammatory markers in plasma. Therefore, a disturbed expression of these regulatory factors may well underlie the disturbed skeletal muscle functioning in chronic obstructive pulmonary disease.

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  • Remels and colleagues observed low levels of PGC1-α and TFAM in COPD quadriceps; these differences were further enhanced in cachectic COPD patients.

    “Remels and colleagues observed low levels of peroxisome proliferator-activated receptor-gamma coactivator 1 alpha (PGC1-α, the master regulator of mitochondrial biogenesis) and its downstream effector, mitochondrial transcription factor A (TFAM), in COPD quadriceps; these differences were further enhanced in cachectic COPD patients [90].”

    From Main Pathogenic Mechanisms and Recent Advances in COPD Peripheral Skeletal Muscle Wasting (2023) · cites this paper as [90]

    The Methods section identifies the biopsied muscle as quadriceps. The PGC-1a and TFAM results sections report lower PGC-1a mRNA and TFAM protein in COPD, with a further TFAM reduction in cachectic patients. But PGC-1a mRNA did not differ between cachectic and noncachectic patients, and PGC-1a protein was not measured; the claim overstates the cachexia finding for PGC-1a. (LLM, conf=0.93)

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Research works printed but not linked: 1

  1. Nystrom T, Nygren A, Sjoholm A. Increased levels of tumour necrosis factor-a in type 2 diabetic patients after myocardial infarction are related to endothelial dysfunc- tion. Clin Sci (Lond) 2006; 110: 673-681.

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Authors
Remels, A. H., Schrauwen, P., Broekhuizen, R., Willems, J., Kersten, S., Gosker, H. R., & Schols, A. M.
Affiliations
Maastricht University (NL)
ORCID
Venue
European Respiratory Journal
Publisher
European Respiratory Society (ERS)
Published
2007-04-25
Volume
30
Issue
2
Pages
245-252
ISSN
  • 0903-1936 (ISSN-L)
  • 1399-3003
DOI
10.1183/09031936.00144106
OpenAlex
W2137507155
Cited by
168
References
35
Citations by year
2026: 2 · 2025: 8 · 2024: 1 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 13 · 2019: 9 · 2018: 8 · 2017: 12 · 2016: 12 · 2015: 6 · 2014: 12 · 2013: 14 · 2012: 10
FWCI
4.88
Type
journal article
Language
en
Open access
Locations
  • European Respiratory Journal (publishedVersion)
  • PubMed (publishedVersion)
  • Research Publications (Maastricht University) (publishedVersion, other-oa)
  • Socio-Environmental Systems Modeling (submittedVersion)
  • Research Publications (Maastricht University) (submittedVersion, other-oa)
  • Data Archiving and Networked Services (DANS) (submittedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Muscle Physiology and Disorders
  • Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Chronic Obstructive Pulmonary Disease (COPD) Research
  • Health Sciences › Medicine › Physiology › Nutrition and Health in Aging
Keywords
chronic obstructive pulmonary disease, skeletal muscle, cachexia, PPARγ, PPARδ, PPARα, PGC-1α, TFAM, mitochondrial biogenesis, muscle weakness, systemic inflammation, gene expression
MeSH terms
Aged, Analysis of Variance, Body Composition, DNA-Binding Proteins, Enzyme-Linked Immunosorbent Assay, Female, Humans, Male, Middle Aged, Phenotype, Respiratory Function Tests, Transcription Factors, Tumor Necrosis Factor-alpha, Blotting, Western, Case-Control Studies, Muscle, Skeletal, Reverse Transcriptase Polymerase Chain Reaction, Mitochondrial Proteins, Pulmonary Disease, Chronic Obstructive, Peroxisome Proliferator-Activated Receptors

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