PGC-1α: Important for exercise performance?

Since the identification of the transcriptional co-activator peroxisome proliferator activated receptor y co-activator (PGC)-1α as a factor interacting with PPARy in brown adipose tissue (BAT) (12), it has become clear that PGC-1α plays important roles in regulating several cellular processes in many different tissues (10) including mitochondrial biogenesis in skeletal muscle (1; 9) Previously, muscle-specific overexpression of PGC-1α resulted in the conversion of otherwise “white” glycolytic muscles to “red” oxidative muscle with a dramatic upregulation of typical oxidative genes/proteins like cytochrome c and cytochrome oxidase (9). These compelling findings indicated that simply overexpressing PGC-1α results in muscle characteristics usually found in highly endurance trained muscle. It was in fact proposed that induction of PGC-1α might be used as “an exercise pill” providing the beneficial effects of exercise training without having to leave the couch (www.wired.com/medtech/health/news/2002/04/51729). The importance of PGC-1α in regulating mitochondrial biogenesis in skeletal muscle has further been underlined by the reduced expression of genes/proteins involved in oxidative metabolism in skeletal muscle of both whole body and muscle-specific PGC-1α knockout mice (1; 4; 8). Moreover, the physiological impact of these modifications in skeletal muscle has consistently been reported by reduced exercise capacity of both whole body and muscle-specific PGC-1α mice (4; 8). In this issue of Journal of Applied Physiology, Calvo et al (3) address the effects of increased muscle PGC-1α levels on exercise performance. Mice with musclespecific over-expression of PGC-1α (MCK-PGC-1α) demonstrated marked improvements in exercise performance both during submaximal exercise intensities and during graded exercise to exhaustion. Intriguingly, the MCK-PGC-1α mice exhibited lower RER values during submaximal as well as maximal exercise intensities reflecting that the molecular Articles in PresS. J Appl Physiol (March 6, 2008). doi:10.1152/japplphysiol.90346.2008