Resistance exercise (RE) activates signalling by the mammalian target of rapamycin (mTOR) and it has been suggested that rapamycin-sensitive mTOR signalling controls RE-induced changes in protein synthesis, ribosome biogenesis, autophagy and the expression of peroxisome proliferator gamma coactivator 1 alpha (PGC-1α). However, direct evidence to support the aforementioned relationships is lacking. Therefore, in this study, we investigated the role of rapamycin-sensitive mTOR in the RE-induced activation of muscle protein synthesis, ribosome biogenesis, PGC-1α expression and hypertrophy. The results indicated that the inhibition of rapamycin-sensitive mTOR could prevent the induction of ribosome biogenesis by RE, but it only partially inhibited the activation of muscle protein synthesis. Likewise, the inhibition of rapamycin-sensitive mTOR only partially blocked the hypertrophic effects of chronic RE. Furthermore, both acute and chronic RE promoted an increase in PGC-1α expression and these alterations were not affected by the inhibition of rapamycin-sensitive mTOR. Combined, the results from this study not only establish that rapamycin-sensitive mTOR plays an important role in the RE-induced activation of protein synthesis and the induction of hypertrophy, but they also demonstrate that additional (rapamycin-sensitive mTOR-independent) mechanisms contribute to these fundamentally important events.

We demonstrated that mitochondrial 4‐hydroxynonenal and protein carbonyls, markers of oxidative stress, were robustly elevated in aged Nrf2 knockout mice, due to the decreased expression of Nrf2‐targ...

To examine the potential role of lactate as a signalling molecule in skeletal muscle, we performed global gene expression analysis of the mouse gastrocnemius muscle, 3 h after lactate administration using the Affymetrix GeneChip system (Affymetrix, Santa Clara, Calif., USA). Among the top 15 genes with the largest fold change, increased expression of Ppargc1a, Pdk4, and Ucp3 was confirmed using real-time quantitative polymerase chain reaction. Our findings suggest that lactate serves as a signal for upregulating genes related to mitochondrial function.

It is known that repeated bouts of high-intensity interval training (HIIT) lead to enhanced levels of glycolysis, glycogenesis, and lactate transport proteins in skeletal muscle; however, little is known about the molecular mechanisms underlying these adaptations. To decipher the mechanism leading to improvement of skeletal muscle glycolytic capacity associated with HIIT, we examined the role of hypoxia-inducible factor-1α (Hif-1α), the major transcription factor regulating the expression of genes related to anaerobic metabolism, in the adaptation to HIIT. First, we induced Hif-1α accumulation using ethyl 3,4-dihydroxybenzoate (EDHB) to assess the potential role of Hif-1α in skeletal muscle. Treatment with EDHB significantly increased the protein levels of Hif-1α in gastrocnemius muscles, accompanied by elevated expression of genes related to glycolysis, glycogenesis, and lactate transport. Daily administration of EDHB for 1 wk resulted in elevated glycolytic enzyme activity in gastrocnemius muscles. Second, we examined whether a single bout of HIIT could induce Hif-1α protein accumulation and subsequent increase in the expression of genes related to anaerobic metabolism in skeletal muscle. We observed that the protein levels of Hif-1α and expression of the target genes were elevated 3 h after an acute bout of HIIT in gastrocnemius muscles. Last, we examined the effects of long-term HIIT. We found that long-term HIIT increased the basal levels of Hif-1α as well as the glycolytic capacity in gastrocnemius muscles. Our results suggest that Hif-1α is a key regulator in the metabolic adaptation to high-intensity training.

It is well known that resistance exercise increases muscle protein synthesis and muscle strength. However, little is known about the effect of resistance exercise on mitochondrial dynamics, which is coupled with mitochondrial function. In skeletal muscle, mitochondria exist as dynamic networks that are continuously remodeling through fusion and fission. The purpose of this study was to investigate the effect of acute and chronic resistance exercise, which induces muscle hypertrophy, on the expression of proteins related to mitochondrial dynamics in rat skeletal muscle. Resistance exercise consisted of maximum isometric contraction, which was induced by percutaneous electrical stimulation of the gastrocnemius muscle. Our results revealed no change in levels of proteins that regulate mitochondrial fission (Fis1 and Drp1) or fusion (Opa1, Mfn1, and Mfn2) over the 24-h period following acute resistance exercise. Phosphorylation of Drp1 at Ser616 was increased immediately after exercise (P < 0.01). Four weeks of resistance training (3 times/week) increased Mfn1 (P < 0.01), Mfn2 (P < 0.05), and Opa1 (P < 0.01) protein levels without altering mitochondrial oxidative phosphorylation proteins. These observations suggest that resistance exercise has little effect on mitochondrial biogenesis but alters the expression of proteins involved in mitochondrial fusion and fission, which may contribute to mitochondrial quality control and improved mitochondrial function.