Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD

A.H. Remels, P. Schrauwen, R. Broekhuizen, J. Willems, A.H. Kersten, H.R. Gosker, A.M. Schols

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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-gamma coactivator (PGC)-1 alpha 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-gamma, PPAR-delta and TFAM were measured at the mRNA and protein level by real-time quantitative PCR and Western blotting, respectively. PPAR-alpha and PGC-1 alpha were meansured at the mRNA level. PPAR-delta and TFAM protein content, as well as PGC-1 alpha 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-alpha mRNA expression and decreased TFAM protein and mRNA levels compared with noncachectic COPD patients. In addition, PPAR-alpha 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.
Original languageEnglish
Pages (from-to)245-252
JournalEuropean Respiratory Journal
Volume30
Issue number2
DOIs
Publication statusPublished - 2007

Keywords

  • obstructive pulmonary-disease
  • tumor-necrosis-factor
  • uncoupling protein-3 content
  • factor-alpha
  • transcriptional coactivator
  • body-composition
  • gene-expression
  • ppar-alpha
  • exercise
  • dysfunction

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    Remels, A. H., Schrauwen, P., Broekhuizen, R., Willems, J., Kersten, A. H., Gosker, H. R., & Schols, A. M. (2007). Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD. European Respiratory Journal, 30(2), 245-252. https://doi.org/10.1183/09031936.00144106