PGC-1α mRNA expression is influenced by metabolic perturbation in exercising human skeletal muscle

Abstract

Endurance training leads to many adaptational changes in several tissues. In skeletal muscle, fatty acid usage is enhanced and mitochondrial content is increased. The exact molecular mechanisms regulating these functional and structural changes remain to be elucidated. Contractile activity-induced metabolic perturbation has repeatedly been shown to be important for the induction of mitochondrial biogenesis. Recent reports suggest that the peroxisome proliferator-activated receptor gamma coactivator 1alpha (PGC-1alpha)/mitochondrial transcription factor A (Tfam) pathway is involved in exercise-induced mitochondrial biogenesis. In the present study, nine healthy men performed two 45-min bouts of one-legged knee extension exercise: one bout with restricted blood flow, and the other with nonrestricted blood flow to the working muscle. Muscle biopsies were obtained from the vastus lateralis muscle before exercise and at 0, 30, 120, and 360 min after the exercise bout. Biopsies were analyzed for whole muscle, as well as fiber-type specific mRNA expression of myocyte-enriched calcineurin interacting protein (MCIP)-1, PGC-1alpha, and downstream mitochondrial transcription factors. A novel finding was that, in human skeletal muscle, PGC-1alpha mRNA increased more after exercise with restricted blood flow than in the nonrestricted condition. No changes were observed for the mRNA of NRF-1, Tfam, mitochondrial transcription factor B1, and mitochondrial transcription factor B2. Muscle fiber type I and type II did not differ in the basal PGC-1alpha mRNA levels or in the expression increase after ischemic training. Another novel finding was that there was no difference between the restricted and nonrestricted exercise conditions in the increase of MCIP-1 mRNA, a marker for calcineurin activation. This suggests that calcineurin may be activated by exercise in humans and does not exclude that calcineurin could play a role in PGC-1 transcription activation in human skeletal muscle.

Suppression of plasma free fatty acids upregulates peroxisome proliferator-activated receptor (PPAR) α and δ and PPAR coactivator 1α in human skeletal muscle, but not lipid regulatory genes

“…There is currently considerable interest in the role of PGC1 in numerous cellular functions, including mitochondrial biogenesis and lipid metabolism, and evidence is emerging linking muscle insulin resistance with mitochondrial dysfunction (Petersen et al 2003). Both acute (Baar et al 2002, Terada et al 2002, Pilegaard et al 2003, Norrbom et al 2004) and chronic (Goto et al 2000, Russell et al 2003, Short et al 2003, Terada & Tabata 2004) exercise increase PGC1 mRNA. In the present study we observed an 12-fold increase in PGC1 mRNA immediately following 3 h of cycle exercise in CON and have extended previous studies by demonstrating an 70% increase (P=0·09, n=5) of PGC1 protein content immediately after acute exercise.…”

Irisin and FNDC5: effects of 12-week strength training, and relations to muscle phenotype and body mass composition in untrained women

“…In fact, an association with traits such as muscle fiber composition seems likely, as its transcriptional regulator PGC-1α has been suggested to show muscle fiber-specific expression, being associated with slow fibers in rodents (Lin et al 2002) and also in humans (Krämer et al 2006), though the latter remains controversial (Plomgaard et al 2006;Norrbom et al 2004). An association between FNDC5 expression and aerobic fibers has indeed been indicated in rodents (Wrann et al 2013;Roca-Rivada et al 2013).…”

Transverse aortic constriction leads to accelerated heart failure in mice lacking PPAR-γ coactivator 1α

“…PGC-1␣ is induced by exercise in skeletal muscle (e.g., refs. [15][16][17][18], and when expressed transgenically in skeletal muscle, it induces a switch in fibers toward more oxidative types I and IIa (19). PGC-1␣ is induced in the fasted liver, where it induces the mitochondrial beta oxidation of fatty acids and also stimulates the entire program of gluconeogenesis (20,21).…”