Expression of PPAR mRNA and protein levels in skeletal muscle of patients with chronic obstructive pulmonary disease (COPD)

Abstract

It is recognized that COPD is a multi-organ systemic disease. Typical systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. Information on the molecular regulation of skeletal muscle abnormalities in these patients is limited. Recent evidence suggests involvement of the peroxisome proliferator-activated receptors (PPARs) in the regulation of skeletal muscle morphology and metabolism. The aim of this exploratory study was therefore to compare the expression of PPARs in skeletal muscle of 14 COPD patients (GOLD stage II-IV; age: 62 ± 12y), stratified by cachexia and 9 age-matched healthy subjects. PPAR-ä protein expression was decreased (p<0.05) in skeletal muscle of COPD patients vs controls. The cachectic COPD subgroup was further characterized by decreased PPAR-α mRNA expression when compared with non cachectic patients (p<0.01) and healthy controls (p<0.01). In patients, PPAR-α mRNA content was inversely related to TNF-α (r = −0.576; p<0.05) and soluble TNF-receptors 75 and 55 (r = −0.546; p<0.05 and r = −0.606; p<0.05) in peripheral blood. These results indicate a potential role for the PPARs in altered molecular regulation of muscle mass and metabolism in patients with COPD and particularly in those suffering from cachexia. This abstract was sponsored by Numico Research and ENIGMA grant QLK6-CT-2002-02285 Email: a.remels@pul.unimaas.nl