Expression and content of PPARs is reduced in skeletal muscle of COPD patients

¹ Dept of Respiratory Medicine, University of Maastricht, the Netherlands
² Dept of Human Biology, University of Maastricht, the Netherlands
³ Nutrition, Metabolism and Genomics Group, Wageningen University, the Netherlands

^* To whom correspondence should be addressed. E-mail: a.remels{at}pul.unimaas.nl.

	Abstract

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- co-activator (PGC-1) 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-, PPAR-, PPAR-, PGC-1 and Tfam were measured at the mRNA and protein level by real time QPCR and western blotting respectively.

PPAR- and Tfam protein content as well as PGC-1 mRNA levels were decreased in skeletal muscle of COPD patients vs healthy controls. The cachectic COPD subgroup was further characterised by decreased PPAR- mRNA expression and decreased Tfam protein and mRNA levels when compared to non cachectic COPD patients. In addition, PPAR- 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.

Keywords:  Chronic Obstructive Pulmonary Disease, mitochondrial transcription factor A, peroxisome proliferator activated receptors, PGC-1, skeletal muscle oxidative capacity

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