Peroxisome proliferator-activated receptor expression is reduced in skeletal muscle in COPD.
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)-1alpha 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-1alpha were meansured at the mRNA level. PPAR-delta and TFAM protein content, as well as PGC-1alpha 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.
Remels
A H
AH
Department of Respiratory Medicine, University of Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. a.remels@pul.unimaas.nl
Schrauwen
P
P
Broekhuizen
R
R
Willems
J
J
Kersten
S
S
Gosker
H R
HR
Schols
A M
AM
D000368:Aged; D000704:Analysis of Variance; D015153:Blotting, Western; D001823:Body Composition; D016022:Case-Control Studies; D004268:DNA-Binding Proteins / Q000378:metabolism*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D024101:Mitochondrial Proteins / Q000378:metabolism*; D018482:Muscle, Skeletal / Q000378:metabolism*; D047492:Peroxisome Proliferator-Activated Receptors / Q000378:metabolism*; D010641:Phenotype; D029424:Pulmonary Disease, Chronic Obstructive / Q000378:metabolism*; D012129:Respiratory Function Tests; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D004268:DNA-Binding Proteins; D024101:Mitochondrial Proteins; D047492:Peroxisome Proliferator-Activated Receptors; C499631:TFAM protein, human; D014157:Transcription Factors; D014409:Tumor Necrosis Factor-alpha; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1