Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle

Abstract

Fyfe JJ, Bishop DJ, Zacharewicz E, Russell AP, Stepto NK. Concurrent exercise incorporating high-intensity interval or continuous training modulates mTORC1 signaling and microRNA expression in human skeletal muscle. Am J Physiol Regul Integr Comp Physiol 310: R1297-R1311, 2016. First published April 13, 2016 doi:10.1152/ajpregu.00479.2015.-We compared the effects of concurrent exercise, incorporating either high-intensity interval training (HIT) or moderate-intensity continuous training (MICT), on mechanistic target of rapamycin complex 1 (mTORC1) signaling and microRNA expression in skeletal muscle, relative to resistance exercise (RE) alone. Eight males (mean Ϯ SD: age, 27 Ϯ 4 yr; V O2 peak, 45.7 Ϯ 9 ml·kg Ϫ1 ·min Ϫ1 ) performed three experimental trials in a randomized order: 1) RE (8 ϫ 5 leg press repetitions at 80% 1-repetition maximum) performed alone and RE preceded by either 2) HIT cycling [10 ϫ 2 min at 120% lactate threshold (LT); HIT ϩ RE] or 3) work-matched MICT cycling (30 min at 80% LT; MICT ϩ RE). Vastus lateralis muscle biopsies were obtained immediately before RE, either without (REST) or with (POST) preceding endurance exercise and ϩ1 h (RE ϩ 1 h) and ϩ3 h (RE ϩ 3 h) after RE. Prior HIT and MICT similarly reduced muscle glycogen content and increased ACC Ser79 and p70S6K Thr389 phosphorylation before subsequent RE (i.e., at POST). Compared with MICT, HIT induced greater mTOR Ser2448 and rps6 Ser235/236 phosphorylation at POST. REinduced increases in p70S6K and rps6 phosphorylation were not influenced by prior HIT or MICT; however, mTOR phosphorylation was reduced at RE ϩ 1 h for MICT ϩ RE vs. both HIT ϩ RE and RE. Expression of miR-133a, miR-378, and miR-486 was reduced at RE ϩ 1 h for HIT ϩ RE vs. both MICT ϩ RE and RE. Postexercise mTORC1 signaling following RE is therefore not compromised by prior HIT or MICT, and concurrent exercise incorporating HIT, but not MICT, reduces postexercise expression of miRNAs implicated in skeletal muscle adaptation to RE. concurrent training; interference; exercise intensity; high-intensity interval training; continuous training INCORPORATING BOTH RESISTANCE (RE) and endurance exercise into a periodized training program is termed concurrent training (56). Compared with undertaking RE alone, concurrent training attenuates skeletal muscle hypertrophy and maximal strength development in some (10,19,33,48,53), but not all (5,58,63,75,76), studies. Given that skeletal muscle mass plays an important role in overall metabolic health (87), and many athletes require elements of strength and muscle hypertrophy, concomitantly with a high aerobic capacity (47), minimizing interference during concurrent training has implications for optimizing both health and performance outcomes.

Enhanced skeletal muscle ribosome biogenesis, yet attenuated mTORC1 and ribosome biogenesis-related signalling, following short-term concurrent versus single-mode resistance training

“…In contrast to previous studies in untrained or relatively training-unaccustomed participants 14 , 16 – 18 , we observed enhanced mTORC1 signalling after resistance training compared with concurrent exercise, including greater mTOR and p70S6K1 phosphorylation at 1 h post-exercise, and rps6 phosphorylation at 3 h post-exercise. These observations contrast with previous data, including our own 20 , showing no differences in mTORC1 signalling responses to single bouts of resistance exercise, performed alone or after a bout of continuous endurance exercise 13 . It has been suggested that any tendency for mTORC1 signalling responses (e.g., p70S6K Thr389 phosphorylation) to be further enhanced by concurrent exercise (relative to resistance exercise alone) before training, as shown in a previous study 14 , were lessened when exercise was performed in a training-accustomed state 13 .…”

“…The magnitude of effects were defined according to thresholds suggested by Hopkins 62 , whereby <0.2 = trivial, 0.2–0.6 = small, 0.6–1.2 = moderate, 1.2–2.0 = large, 2.0–4.0 = very large and >4.0 = extremely large effects. Lacking information on the smallest meaningful effect for changes in protein phosphorylation and gene expression, the threshold for the smallest worthwhile effect was defined as an ES of 0.4, rather than the conventional threshold of 0.2 20 . Magnitude-based inferences about effects were made by qualifying the effects with probabilities reflecting the uncertainty in the magnitude of the true effect 63 .…”

“…Several studies, however, have demonstrated that single sessions of concurrent exercise do not compromise either mTORC1 signalling or rates of MPS 9 , 10 , 16 – 18 , and may even potentiate these responses 14 , compared with resistance exercise performed alone. However, a limitation of these studies is that most have examined these responses in either untrained individuals 16 – 18 or those who are relatively unaccustomed to the exercise protocol 14 , 20 . Given short-term training increases the mode-specificity of post-exercise molecular responses 21 , 22 , examining perturbations to molecular signalling and gene expression in relatively training-unaccustomed individuals may confound any insight into the potential molecular mechanisms responsible for interference following concurrent training 23 .…”

The Role of Intra-Session Exercise Sequence in the Interference Effect: A Systematic Review with Meta-Analysis

“…Further, the search of English-language sources only might have resulted in missed data. Furthermore, the role of exercise intensity within the context of the interference effect is a topical area of research [ 35 , 36 ]. It is possible that the relatively untrained cohorts included in the meta-analysis were limited by their ability to perform at higher exercise intensities, and the subsequent effect that this could have had on the interference effect or benefit of a given intra-session exercise order is unknown.…”

High‐intensity interval training in chronic kidney disease: A randomized pilot study

“…15 Further, it has previously been shown that in healthy males, HIIT is a stimulus for increased anabolic response by activating mTOR, leading to p70S6k activation. 16 To date, only one study has investigated the feasibility of higher intensity exercise in patients with CKD. 17 It was shown that patients with lower hemoglobin and exercise capacity, which are common with CKD, were a limiting factor in completing higher intensity exercise (not HIIT).…”