Repeated transient mRNA bursts precede increases in transcriptional and mitochondrial proteins during training in human skeletal muscle

Abstract

Exercise training induces mitochondrial biogenesis, but the time course of molecular sequelae that accompany repetitive training stimuli remains to be determined in human skeletal muscle. Therefore, throughout a seven-session, high-intensity interval training period that increaseḋ V O 2 max (12%), we examined the time course of responses of (a) mitochondrial biogenesis and fusion and fission proteins, and (b) selected transcriptional and mitochondrial mRNAs and proteins in human muscle. Muscle biopsies were obtained 4 and 24 h after the 1st, 3rd, 5th and 7th training session. PGC-1α mRNA was increased >10-fold 4 h after the 1st session and returned to control within 24 h. This 'saw-tooth' pattern continued until the 7th bout, with smaller increases after each bout. In contrast, PGC-1α protein was increased 24 h after the 1st bout (23%) and plateaued at +30-40% between the 3rd and 7th bout. Increases in PGC-1β mRNA and protein were more delayed and smaller, and did not persist. Distinct patterns of increases were observed in peroxisome proliferator-activated receptor (PPAR) α and γ protein (1 session), PPAR β/δ mRNA and protein (5 sessions) and nuclear respiratory factor-2 protein (3 sessions) while no changes occurred in mitochondrial transcription factor A protein. Citrate synthase (CS) and β-HAD mRNA were rapidly increased (1 session), followed 2 sessions later (session 3) by increases in CS and β-HAD activities, and mitochondrial DNA. Changes in COX-IV mRNA (session 3) and protein (session 5) were more delayed. Training also increased mitochondrial fission proteins (fission protein-1, >2-fold; dynamin-related protein-1, 47%) and the fusion protein mitofusin-1 (35%) but not mitofusin-2. This study has provided the following novel information: (a) the training-induced increases in transcriptional and mitochondrial proteins appear to result from the cumulative effects of transient bursts in their mRNAs, (b) training-induced mitochondrial biogenesis appears to involve re-modelling in addition to increased mitochondrial content, and (c) the 'transcriptional capacity' of human muscle is extremely sensitive, being activated by one training bout.

New strategies in sport nutrition to increase exercise performance

“…At the level of the muscle a period of endurance training leads to improvements in blood flow, mitochondrial content and an improved ability to extract and utilise oxygen during exercise [7]. These adaptive processes are driven by transcriptional changes in response to each bout of exercise [2,8]. The transcriptional changes accumulate over time such that the protein expression profile of muscle is changed resulting in an altered phenotype [2,8].…”

“…These adaptive processes are driven by transcriptional changes in response to each bout of exercise [2,8]. The transcriptional changes accumulate over time such that the protein expression profile of muscle is changed resulting in an altered phenotype [2,8]. The question then remains as to how contracting skeletal muscle senses the work and conveys that signal to a gene expression change, ultimately resulting in improved fatigue resistance.…”

“…As with endurance exercise, nutrition can play a critical role in augmenting the adaptive stimulus that comes from resistance exercise [84]. Whilst endurance exercise adaptations are believed to be driven primarily by transcriptional responses [2,8], the muscle growth adaptation to resistance exercise is driven primarily by changes in translation, in particular by increases in mRNA activity (protein produced per unit of mRNA) [85][86][87]. The multi-protein complex mechanistic Target of Rapamycin Complex 1 (mTORC1) is a key controller of protein synthesis through the control that it exerts on mRNA activity via increasing protein translation initiation [88] (Figure 2).…”

“…The optimal loading protocol is unknown but intakes of 3-6 g/d for [4][5][6][7][8][9][10][11][12] weeks increase this intracellular buffer by 50-85% [136]. To date, no threshold for carnosine concentrations has been found, but a daily intake of ~ 1.2 g appears to maintain muscle carnosine elevations and a return to baseline may require 6-20 weeks of supplement withdrawal [137].…”

Physiological and molecular responses to an acute bout of reduced-exertion high-intensity interval training (REHIT)

“…At the molecular level, adaptation to exercise is thought to result from cumulative transient increases in gene transcription (and protein synthesis) that follow each acute exercise bout, with the metabolic perturbations induced by contraction activating various signalling kinases which, in turn, target downstream transcriptional coactivators and regulators (Perry et al 2010). Previous studies investigating more time-consuming and more strenuous HIT protocols have demonstrated a molecular response which includes a 20-30% drop in muscle glycogen concentrations, substantial lactate accumulation, an altered ATP:ADP ratio, and increases in AMPK activity (1.4-fold), p38 MAPK activity (1.5-fold), and a 6-fold increase in mRNA expression of PGC1α (Esbjornsson-Liljedahl et al 1999;Gibala et al 2009;Parolin et al 1999).…”