RT Journal Article
SR Electronic
T1 Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD
JF European Respiratory Journal
JO Eur Respir J
FD European Respiratory Society
SP 245
OP 252
DO 10.1183/09031936.00144106
VO 30
IS 2
A1 A. H. Remels
A1 P. Schrauwen
A1 R. Broekhuizen
A1 J. Willems
A1 S. Kersten
A1 H. R. Gosker
A1 A. M. Schols
YR 2007
UL http://erj.ersjournals.com/content/30/2/245.abstract
AB 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.