Acute signalling responses to intense endurance training commenced with low or normal muscle glycogen

Abstract

We have previously demonstrated that well-trained subjects who completed a 3 week training programme in which selected high-intensity interval training (HIT) sessions were commenced with low muscle glycogen content increased the maximal activities of several oxidative enzymes that promote endurance adaptations to a greater extent than subjects who began all training sessions with normal glycogen levels. The aim of the present study was to investigate acute skeletal muscle signalling responses to a single bout of HIT commenced with low or normal muscle glycogen stores in an attempt to elucidate potential mechanism(s) that might underlie our previous observations. Six endurance-trained cyclists/triathletes performed a 100 min ride at ∼70% peak O 2 uptake (AT) on day 1 and HIT (8 × 5 min work bouts at maximal selfselected effort with 1 min rest) 24 h later (HIGH). Another six subjects, matched for fitness and training history, performed AT on day 1 then 1-2 h later, HIT (LOW). Muscle biopsies were taken before and after HIT. Muscle glycogen concentration was higher in HIGH versus LOW before the HIT (390 ± 28 versus 256 ± 67 μmol (g dry wt)−1 ). After HIT, glycogen levels were reduced in both groups (P < 0.05) but HIGH was elevated compared with LOW (229 ± 29 versus 124 ± 41 μmol (g dry wt) −1 ; P < 0.05). Phosphorylation of 5 AMP-activated protein kinase (AMPK) increased after HIT, but the magnitude of increase was greater in LOW (P < 0.05). Despite the augmented AMPK response in LOW after HIT, selected downstream AMPK substrates were similar between groups. Phosphorylation of p38 mitogen-activated protein kinase (p38 MAPK) was unchanged for both groups before and after the HIT training sessions. We conclude that despite a greater activation AMPK phosphorylation when HIT was commenced with low compared with normal muscle glycogen availability, the localization and phosphorylation state of selected downstream targets of AMPK were similar in response to the two interventions.

New strategies in sport nutrition to increase exercise performance

“…Indeed substantial experimental evidence in humans supports this. For example, when exercise is commenced in the glycogen depleted state the phosphorylation of AMPK is greater in the post exercise recovery when muscle glycogen is low [21][22][23]. Interestingly, in rodent studies when exercise occurs in the low glycogen state AMPK nuclear content is increased [24].…”

“…These data have therefore led to the innovative "train-low (or smart), compete-high" model surmising that athletes deliberately complete a portion of their training programme with reduced CHO availability so as to augment training adaptation but yet always ensure high CHO availability prior to and during competition in an attempt to promote maximal performance [64]. The augmented training response observed with training-low strategies are currently thought to be regulated via the enhanced activation of upstream cell signalling kinases including both AMPK [23] and p38MAPK [65] that ultimately converge on the downstream regulation of key transcription factors and coactivators such as PGC-1α [66], p53 [21] and PPARδ [24] (Figure 1). In this way, training with low CHO availability thereby leads to a co-ordinated up-regulation of both the nuclear and mitochondrial genomes.…”

The Emerging Role of p53 in Exercise Metabolism

“…These kinases, acting alone or in combination with each other, can subsequently activate downstream transcription factors and co-activators [19] that exert regulatory roles in co-ordinating the expression of both nuclear and mitochondrial-encoded proteins. Broadly speaking, activation of the aforementioned kinases is dependent on exercise modality [20], intensity [19], duration [21,22], training history [23], training status [24] and nutrient availability [25]. When taken together, these data provide an insight as to the potential molecular mechanisms underpinning some of the well-known training principles, in that training programs should ensure a continual alteration in workload and manipulation of energy provision in order to repeatedly stimulate the necessary signalling pathways required to support sustained muscle adaptation.…”

Reduced carbohydrate availability enhances exercise-induced p53 signaling in human skeletal muscle: implications for mitochondrial biogenesis

“…In considering possible contractile induced stressors for activating the acute cell signaling pathways associated with regulation of mitochondrial biogenesis, reductions in carbohydrate (CHO) availability is now emerging as one of the most potent signals (41). For example, in healthy subjects, the acute exercise-induced activation of the signaling kinases AMPK (60,62) and p38MAPK (8,12) are greater when preexercise glycogen availability is low. Transcription of several metabolic related genes such as PDK4, CPT-1, CD36, GLUT-4, UCP-3, and HSP72 are also enhanced when exercise is completed with reduced CHO availability before and/or during exercise (9,11,13,43).…”