COPD is a multi-organ systemic disease. Systemic features are skeletal muscle weakness and cachexia, the latter being associated with systemic inflammation. Exact mechanisms underlying skeletal muscle dysfunction in COPD remain obscure. Recent evidence suggests involvement of the peroxisome proliferator-activated receptors (PPARs) and PPAR-gamma co-activator (PGC-1alpha) in regulation of skeletal muscle morphology and metabolism while the mitochondrial transcription factor A (Tfam) has been implicated in the process of mitochondrial biogenesis. The aim of this exploratory study was therefore to compare these factors in skeletal muscle of 9 healthy control subjects and 14 COPD patients stratified by cachexia.PPAR-alpha, PPAR-gamma, PPAR-delta, PGC-1alpha and Tfam were measured at the mRNA and protein level by real time QPCR and western blotting respectively.PPAR-delta and Tfam protein content as well as PGC-1alpha mRNA levels were decreased in skeletal muscle of COPD patients vs healthy controls. The cachectic COPD subgroup was further characterised by decreased PPAR-alpha mRNA expression and decreased Tfam protein and mRNA levels when compared to non cachectic COPD patients. In addition, PPAR-alpha mRNA levels in skeletal muscle correlated negatively with inflammatory markers in plasma.Therefore, a disturbed expression and/or content of these regulatory factors may well underlie the disturbed skeletal muscle functioning in COPD.