Muscle-specific expression of PPARγ coactivator-1α improves exercise performance and increases peak oxygen uptake

Abstract

The induction of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a key regulator of mitochondriogenesis, is well-established under multiple physical exercise regimens, including, endurance, resistance, and sprint training. We wanted to determine if increased expression of PGC-1alpha in muscle is sufficient to improve performance during exercise in vivo. We demonstrate that muscle-specific expression of PGC-1alpha improves the performance during voluntary as well as forced exercise challenges. Additionally, PGC-1alpha transgenic mice exhibit an enhanced performance during a peak oxygen uptake exercise test, demonstrating an increased peak oxidative capacity, or whole body oxygen uptake. This increased ability to perform in multiple exercise paradigms is supported by enhanced mitochondrial function as suggested by increased mitochondrial gene expression, mitochondrial DNA, and mitochondrial enzyme activity. Thus this study demonstrates that upregulation of PGC-1alpha in muscle in vivo is sufficient to greatly improve exercise performance under various exercise paradigms as well as increase peak oxygen uptake.

TRPV1 activation improves exercise endurance and energy metabolism through PGC-1α upregulation in mice

“…PGC-1α downregulation was supposed to contribute to both the progression of muscle dysfunction and metabolic disorders. Increased expression of PGC-1α results in increased mitochondrial function and oxidative muscle fibers and protects from metabolic disease during aging [40,41]. The present study shows that with improved endurance capacity, dietary capsaicin also ameliorated the HFD-induced obesity, insulin resistance and glucose and lipid disorders.…”

PGC-1α Mediated Muscle Aerobic Adaptations to Exercise, Heat and Cold Exposure

“…Similar findings were reported by Calvo et al (2008), where mice overexpressing PGC-1α had higher basal mRNA content of β-oxidation proteins (MCAD, LCAD & CD36), compared with wildtype controls. These findings highlight the pivotal role of PGC-1α in the transcriptional control of proteins involved in fatty acid transport and oxidation, consequently enhancing the overall capacity for fatty acid oxidation.…”

“…shown to contain greater muscle mitochondrial content and higher basal mRNA expression of several respiratory chain components such as Cyt c and COX4 when compared with wildtype controls (Calvo et al, 2008). Moreover, PGC-1α overexpressing mice have shown to possess higher maximal oxygen uptake (VO2max) and demonstrated superior exercise capacity during voluntary and forced running (Calvo et al, 2008).…”

“…Moreover, PGC-1α overexpressing mice have shown to possess higher maximal oxygen uptake (VO2max) and demonstrated superior exercise capacity during voluntary and forced running (Calvo et al, 2008). However, loss-of-function studies using whole-body or muscle specific PGC-1α knock-out models have to date demonstrated contradictory results.…”

“…While there are many important factors involved in the biosynthesis of the mitochondrion, the transcriptional coactivator, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) has been identified as a key regulator involved in this highly complex process Puigserver et al, 1998;Wu et al, 1999). Indeed, there is now good evidence demonstrating that exercise-induced mitochondrial biogenesis is modulated via PGC-1α dependant mechanisms (Calvo et al, 2008;Leick et al, 2010;Leick et al, 2008;Little et al, 2011;Safdar et al, 2011;Uguccioni and Hood, 2011;Zhang et al, 2014). Exercise capacity and performance has shown to be strongly associated with muscle mitochondrial content in both animal and human models (Daussin et al, 2008;Fitts et al, 1975) and is associated with improved risk factors for a variety of chronic diseases (Bishop-Bailey, 2013).…”