Adaptations of skeletal muscle to exercise: rapid increase in the transcriptional coactivator PGC‐1

Abstract

Endurance exercise induces increases in mitochondria and the GLUT4 isoform of the glucose transporter in muscle. Although little is known about the mechanisms underlying these adaptations, new information has accumulated regarding how mitochondrial biogenesis and GLUT4 expression are regulated. This includes the findings that the transcriptional coactivator PGC-1 promotes mitochondrial biogenesis and that NRF-1 and NRF-2 act as transcriptional activators of genes encoding mitochondrial enzymes. We tested the hypothesis that increases in PGC-1, NRF-1, and NRF-2 are involved in the initial adaptive response of muscle to exercise. Five daily bouts of swimming induced increases in mitochondrial enzymes and GLUT4 in skeletal muscle in rats. One exercise bout resulted in approximately twofold increases in full-length muscle PGC-1 mRNA and PGC-1 protein, which were evident 18 h after exercise. A smaller form of PGC-1 increased after exercise. The exercise induced increases in muscle NRF-1 and NRF-2 that were evident 12 to 18 h after one exercise bout. These findings suggest that increases in PGC-1, NRF-1, and NRF-2 represent key regulatory components of the stimulation of mitochondrial biogenesis by exercise and that PGC-1 mediates the coordinated increases in GLUT4 and mitochondria.

Effects of intrinsic aerobic capacity, aging and voluntary running on skeletal muscle sirtuins and heat shock proteins

“…Also, as PGC-1 is known to respond to 467 exercise acutely (Baar et al 2002), so as in our study the running distance decreased 468 gradually over time, also the pressure for change decreased (Fig. 3A).…”

“…Endurance exercise training causes adaptations of the cardiorespiratory and neuromuscular systems that enhance the delivery of oxygen from blood to muscles cells, as well as increase the amount and efficiency of muscle mito-chondria (Jones & Carter 2000;Baar et al 2002;Pilegaard, Saltin & Neufer 2003). These adaptations effect an improvement in individuals' aerobic capacity and endurance performance.…”

“…It seems that in the gastrocnemius muscle, there was no stimulus to increase the markers of oxidative capacity to a significant extent, at least not at the time point chosen in our study. Moreover, PGC-1 is known to respond to exercise acutely (Baar et al 2002). It appears in our study that the running distance decreased gradually over time ( Figure 17C) concomitantly with the stimulus for adaptation.…”

Activation of the mitogen-activated protein kinase (MAPK) signalling pathway in the liver of mice is related to plasma glucose levels after acute exercise

“…The transcriptional response of the muscle to one single bout of exercise or contraction as well as to exercise training has been studied extensively. The majority of the differentially expressed genes are involved in glucose and fatty acid metabolism [11][12][13], and in myogenesis [14], the regulation of transcription [15,16] and the stress response [17]. The metabolic adaptation to exercise is not restricted to the working muscle.…”

Physiological variables and mitochondrial-related genotypes of an athlete who excels in both short and long-distance running

“…Evidence from both human (Mahoney et al 2005;Norrbom et al 2004;Russell et al 2003;Short et al 2003) and animal studies (Baar et al 2002;Terada et al 2002) imply that transcription factors and co-activators in the peroxisome proliferator-activated receptor (PPAR)-nuclear respiratory factor (NRF)-mitochondrial transcription Factor A (TFAM) pathway influence endurance performance, due to their key role in regulation of cellular energy metabolism.…”