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Published online before print April 25, 2007, 10.1183/09031936.00144106
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Eur Respir J 2007; 30:245-252
Copyright ©ERS Journals Ltd 2007

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

A. H. Remels1, P. Schrauwen2, R. Broekhuizen1, J. Willems1, S. Kersten3, H. R. Gosker1 and A. M. Schols1

Depts of 1 Respiratory Medicine, and 2 Human Biology, University of Maastricht, Maastricht, and 3 Nutrition, Metabolism and Genomics Group, Wageningen University, Wageningen, The Netherlands.

CORRESPONDENCE: A. H. Remels, Dept of Respiratory Medicine, University of Maastricht, P.O. Box 5800, 6202 AZ Maastricht, The Netherlands. Fax: 31 433875051. E-mail: a.remels{at}pul.unimaas.nl

Keywords: Chronic obstructive pulmonary disease, mitochondrial transcription factor A, peroxisome proliferator-activated receptors, peroxisome proliferator-activated receptor-{gamma} coactivator-1{alpha}, skeletal muscle oxidative capacity

Received: November 6, 2006
Accepted April 6, 2007

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.




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A. H. Remels, H. R. Gosker, P. Schrauwen, R. C. Langen, and A. M. Schols
Peroxisome proliferator-activated receptors: a therapeutic target in COPD?
Eur. Respir. J., March 1, 2008; 31(3): 502 - 508.
[Abstract] [Full Text] [PDF]




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