Caffeine ingestion and cycling power output in a low or normal muscle glycogen state

Purpose Commencing selected workouts with low muscle glycogen availability augments several markers of training adaptation compared with undertaking the same sessions with normal glycogen content. However, low glycogen availability reduces the capacity to perform high-intensity (>85% of peak aerobic power (V·O2peak)) endurance exercise. We determined whether a low dose of caffeine could partially rescue the reduction in maximal self-selected power output observed when individuals commenced high-intensity interval training with low (LOW) compared with normal (NORM) glycogen availability. Methods Twelve endurance-trained cyclists/triathletes performed four experimental trials using a double-blind Latin square design. Muscle glycogen content was manipulated via exercise–diet interventions so that two experimental trials were commenced with LOW and two with NORM muscle glycogen availability. Sixty minutes before an experimental trial, subjects ingested a capsule containing anhydrous caffeine (CAFF, 3 mg-1·kg-1 body mass) or placebo (PLBO). Instantaneous power output was measured throughout high-intensity interval training (8 × 5-min bouts at maximum self-selected intensity with 1-min recovery). Results There were significant main effects for both preexercise glycogen content and caffeine ingestion on power output. LOW reduced power output by approximately 8% compared with NORM (P < 0.01), whereas caffeine increased power output by 2.8% and 3.5% for NORM and LOW, respectively, (P < 0.01). Conclusion We conclude that caffeine enhanced power output independently of muscle glycogen concentration but could not fully restore power output to levels commensurate with that when subjects commenced exercise with normal glycogen availability. However, the reported increase in power output does provide a likely performance benefit and may provide a means to further enhance the already augmented training response observed when selected sessions are commenced with reduced muscle glycogen availability. It has long been known that endurance training induces a multitude of metabolic and morphological adaptations that improve the resistance of the trained musculature to fatigue and enhance endurance capacity and/or exercise performance (13). Accumulating evidence now suggests that many of these adaptations can be modified by nutrient availability (9–11,21). Growing evidence suggests that training with reduced muscle glycogen using a “train twice every second day” compared with a more traditional “train once daily” approach can enhance the acute training response (29) and markers representative of endurance training adaptation after short-term (3–10 wk) training interventions (8,16,30). Of note is that the superior training adaptation in these previous studies was attained despite a reduction in maximal self-selected power output (16,30). The most obvious factor underlying the reduced intensity during a second training bout is the reduction in muscle glycogen availability. However, there is also the possibility that other metabolic and/or neural factors may be responsible for the power drop-off observed when two exercise bouts are performed in close proximity. Regardless of the precise mechanism(s), there remains the intriguing possibility that the magnitude of training adaptation previously reported in the face of a reduced training intensity (Hulston et al. (16) and Yeo et al.) might be further augmented, and/or other aspects of the training stimulus better preserved, if power output was not compromised. Caffeine ingestion is a possible strategy that might “rescue” the aforementioned reduction in power output that occurs when individuals commence high-intensity interval training (HIT) with low compared with normal glycogen availability. Recent evidence suggests that, at least in endurance-based events, the maximal benefits of caffeine are seen at small to moderate (2–3 mg·kg-1 body mass (BM)) doses (for reviews, see Refs. (3,24)). Accordingly, in this study, we aimed to determine the effect of a low dose of caffeine (3 mg·kg-1 BM) on maximal self-selected power output during HIT commenced with either normal (NORM) or low (LOW) muscle glycogen availability. We hypothesized that even under conditions of low glycogen availability, caffeine would increase maximal self-selected power output and thereby partially rescue the reduction in training intensity observed when individuals commence HIT with low glycogen availability.

mTOR function in skeletal muscle : a focal point for overnutrition and exercise

The mammalian target of rapamycin (mTOR) is a highly conserved atypical serine-threonine kinase that controls numerous functions essential for cell homeostasis and adaptation in mammalian cells via 2 distinct protein complex formations. Moreover, mTOR is a key regulatory protein in the insulin signalling cascade and has also been characterized as an insulin-independent nutrient sensor that may represent a critical mediator in obesity-related impairments of insulin action in skeletal muscle. Exercise characterizes a remedial modality that enhances mTOR activity and subsequently promotes beneficial metabolic adaptation in skeletal muscle. Thus, the metabolic effects of nutrients and exercise have the capacity to converge at the mTOR protein complexes and subsequently modify mTOR function. Accordingly, the aim of the present review is to highlight the role of mTOR in the regulation of insulin action in response to overnutrition and the capacity for exercise to enhance mTOR activity in skeletal muscle.

Global gene expression in skeletal muscle from well-trained strength and endurance athletes

PURPOSE: We used gene microarray analysis to compare the global expression profile of genes involved in adaptation to training in skeletal muscle from chronically strength-trained (ST), endurance-trained (ET), and untrained control subjects (Con). METHODS: Resting skeletal muscle samples were obtained from the vastus lateralis of 20 subjects (Con n = 7, ET n = 7, ST n = 6; trained [TR] groups >8 yr specific training). Total RNA was extracted from tissue for two color microarray analysis and quantative (Q)-PCR. Trained subjects were characterized by performance measures of peak oxygen uptake V?O 2peak) on a cycle ergometer and maximal concentric and eccentric leg strength on an isokinetic dynamometer. RESULTS: Two hundred and sixty-three genes were differentially expressed in trained subjects (ET + ST) compared with Con (P < 0.05), whereas 21 genes were different between ST and ET (P < 0.05). These results were validated by reverse transcriptase polymerase chain reaction for six differentially regulated genes (EIFSJ, LDHB, LMO4, MDH1, SLC16A7, and UTRN. Manual cluster analyses revealed significant regulation of genes involved in muscle structure and development in TR subjects compared with Con (P < 0.05) and expression correlated with measures of performance (P < 0.05). ET had increased whereas ST had decreased expression of gene clusters related to mitochondrial/oxidative capacity (P ?‰Currency sign 0.05). These mitochondrial gene clusters correlated with V?O2peak (P < 0.05). V?O2peak also correlated with expression of gene clusters that regulate fat and carbohydrate oxidation (P < 0.05). CONCLUSION: We demonstrate that chronic training subtly coregulates numerous genes from important functional groups that may be part of the long-term adaptive process to adapt to repeated training stimuli.

The molecular bases of training adaptation

Skeletal muscle is a malleable tissue capable of altering the type and amount of protein in response to disruptions to cellular homeostasis. The process of exercise-induced adaptation in skeletal muscle involves a multitude of signalling mechanisms initiating replication of specific DNA genetic sequences, enabling subsequent translation of the genetic message and ultimately generating a series of amino acids that form new proteins. The functional consequences of these adaptations are determined by training volume, intensity and frequency, and the half-life of the protein. Moreover, many features of the training adaptation are specific to the type of stimulus, such as the mode of exercise. Prolonged endurance training elicits a variety of metabolic and morphological changes, including mitochondrial biogenesis, fast-to-slow fibre-type transformation and substrate metabolism. In contrast, heavy resistance exercise stimulates synthesis of contractile proteins responsible for muscle hypertrophy and increases in maximal contractile force output. Concomitant with the vastly different functional outcomes induced by these diverse exercise modes, the genetic and molecular mechanisms of adaptation are distinct. With recent advances in technology, it is now possible to study the effects of various training interventions on a variety of signalling proteins and early-response genes in skeletal muscle. Although it cannot presently be claimed that such scientific endeavours have influenced the training practices of elite athletes, these new and exciting technologies have provided insight into how current training techniques result in specific muscular adaptations, and may ultimately provide clues for future and novel training methodologies. Greater knowledge of the mechanisms and interaction of exercise-induced adaptive pathways in skeletal muscle is important for our understanding of the aetiology of disease, maintenance of metabolic and functional capacity with aging, and training for athletic performance. This article highlights the effects of exercise on molecular and genetic mechanisms of training adaptation in skeletal muscle.

Effect of exercise training on skeletal muscle cytokine expression in the elderly

Aging is associated with increased circulating pro-inflammatory and lower anti-inflammatory cytokines. Exercise training, in addition to improving muscle function, reduces these circulating pro-inflammatory cytokines. Yet, few studies have evaluated changes in the expression of cytokines within skeletal muscle after exercise training. The aim of the current study was to examine the expression of cytokines both at rest and following a bout of isokinetic exercise performed before and after 12 weeks of resistance exercise training in young (n = 8, 20.3 ± 0.8 yr) and elderly men (n = 8, 66.9 ± 1.6 yr). Protein expression of various cytokines was determined in muscle homogenates. The expression of MCP-1, IL-8 and IL-6 (which are traditionally classified as ‘pro-inflammatory’) increased substantially after acute exercise. By contrast, the expression of the anti-inflammatory cytokines IL-4, IL-10 and IL-13 increased only slightly (or not at all) after acute exercise. These responses were not significantly different between young and elderly men, either before or after 12 weeks of exercise training. However, compared with the young men, the expression of pro-inflammatory cytokines 2 h post exercise tended to be greater in the elderly men prior to training. Training attenuated this difference. These data suggest that the inflammatory response to unaccustomed exercise increases with age. Furthermore, regular exercise training may help to normalize this inflammatory response, which could have important implications for muscle regeneration and adaptation in the elderly.

Functional adaptation and rehabilitation following total knee replacement

This research project evaluated the biomechanical and functional outcomes of patients following total knee replacement measured at 6 and 12 months following surgery. Using more objective measures, patients were examined to determine changes in biomechanical and neuromuscular function during performance of activities of daily living such as walking, stair climbing and turning. Adaptations in joint positioning and performance were identified and progressive improvements were made in some areas of locomotor function. The findings of the study provided important objective information to contribute to the design and evaluation of prostheses, new surgical and rehabilitation procedures and improved recovery of patients.

Impedance control balances stability with metabolically costly muscle activation.

Humans are able to stabilize their movements in environments with unstable dynamics by selectively modifying arm impedance independently of force and torque. We further investigated adaptation to unstable dynamics to determine whether the CNS maintains a constant overall level of stability as the instability of the environmental dynamics is varied. Subjects performed reaching movements in unstable force fields of varying strength, generated by a robotic manipulator. Although the force fields disrupted the initial movements, subjects were able to adapt to the novel dynamics and learned to produce straight trajectories. After adaptation, the endpoint stiffness of the arm was measured at the midpoint of the movement. The stiffness had been selectively modified in the direction of the instability. The stiffness in the stable direction was relatively unchanged from that measured during movements in a null force field prior to exposure to the unstable force field. This impedance modification was achieved without changes in force and torque. The overall stiffness of the arm and environment in the direction of instability was adapted to the force field strength such that it remained equivalent to that of the null force field. This suggests that the CNS attempts both to maintain a minimum level of stability and minimize energy expenditure.

Impedance control and internal model use during the initial stage of adaptation to novel dynamics in humans.

This study investigated the neuromuscular mechanisms underlying the initial stage of adaptation to novel dynamics. A destabilizing velocity-dependent force field (VF) was introduced for sets of three consecutive trials. Between sets a random number of 4-8 null field trials were interposed, where the VF was inactivated. This prevented subjects from learning the novel dynamics, making it possible to repeatedly recreate the initial adaptive response. We were able to investigate detailed changes in neural control between the first, second and third VF trials. We identified two feedforward control mechanisms, which were initiated on the second VF trial and resulted in a 50% reduction in the hand path error. Responses to disturbances encountered on the first VF trial were feedback in nature, i.e. reflexes and voluntary correction of errors. However, on the second VF trial, muscle activation patterns were modified in anticipation of the effects of the force field. Feedforward cocontraction of all muscles was used to increase the viscoelastic impedance of the arm. While stiffening the arm, subjects also exerted a lateral force to counteract the perturbing effect of the force field. These anticipatory actions indicate that the central nervous system responds rapidly to counteract hitherto unfamiliar disturbances by a combination of increased viscoelastic impedance and formation of a crude internal dynamics model.

Generalization in Adaptation to Stable and Unstable Dynamics

Humans skillfully manipulate objects and tools despite the inherent instability. In order to succeed at these tasks, the sensorimotor control system must build an internal representation of both the force and mechanical impedance. As it is not practical to either learn or store motor commands for every possible future action, the sensorimotor control system generalizes a control strategy for a range of movements based on learning performed over a set of movements. Here, we introduce a computational model for this learning and generalization, which specifies how to learn feedforward muscle activity in a function of the state space. Specifically, by incorporating co-activation as a function of error into the feedback command, we are able to derive an algorithm from a gradient descent minimization of motion error and effort, subject to maintaining a stability margin. This algorithm can be used to learn to coordinate any of a variety of motor primitives such as force fields, muscle synergies, physical models or artificial neural networks. This model for human learning and generalization is able to adapt to both stable and unstable dynamics, and provides a controller for generating efficient adaptive motor behavior in robots. Simulation results exhibit predictions consistent with all experiments on learning of novel dynamics requiring adaptation of force and impedance, and enable us to re-examine some of the previous interpretations of experiments on generalization. © 2012 Kadiallah et al.

Neuromuscular adaptation during skill acquisition on a two degree-of-freedom target-acquisition task: Isometric torque production

In this study we attempted to identify the principles that govern the changes in neural control that occur during repeated performance of a multiarticular coordination task. Eight participants produced isometric flexion/extension and pronation/supination torques at the radiohumeral joint, either in isolation (e.g., flexion) or in combination (e.g., flexion - supination), to acquire targets presented by a visual display. A cursor superimposed on the display provided feedback of the applied torques. During pre- and postpractice tests, the participants acquired targets in eight directions located either 3.6 cm (20% maximal voluntary contraction [MVC]) or 7.2 cm (40% MVC) from a neutral cursor position. On each of five consecutive days of practice the participants acquired targets located 5.4 cm (30% MVC) from the neutral position. EMG was recorded from eight muscles contributing to torque production about the radiohumeral joint during the pre- and posttests. Target-acquisition time decreased significantly with practice in most target directions and at both target torque levels. These performance improvements were primarily associated with increases in the peak rate of torque development after practice. At a muscular level, these changes were brought about by increases in the rates of recruitment of all agonist muscles. The spatiotemporal organization of muscle synergies was not significantly altered after practice. The observed adaptations appear to lead to performances that are generalizable to actions that require both greater and smaller joint torques than that practiced, and may be successfully recalled after a substantial period without practice. These results suggest that tasks in which performance is improved by increasing the rate of muscle activation, and thus the rate of joint torque development, may benefit in terms of the extent to which acquired levels of performance are maintained over time.

Neuromuscular adaptation during skill acquisition on a two degree-of-freedom target-acquisition task: Dynamic movement

In this experiment, we examined the extent to which the spatiotemporal reorganization of muscle synergies mediates skill acquisition on a two degree-of-freedom (df) target-acquisition task. Eight participants completed five practice sessions on consecutive days. During each session they practiced movements to eight target positions presented by a visual display. The movements required combinations of flexion/extension and pronation/supination of the elbow joint complex. During practice sessions, eight targets displaced 5.4 cm from the start position ( representing joint excursions of 54) were presented 16 times. During pre- and posttests, participants acquired the targets at two distances (3.6 cm [36 degrees] and 7.2 cm [72 degrees]). EMG data were recorded from eight muscles contributing to the movements during the pre- and posttests. Most targets were acquired more rapidly after the practice period. Performance improvements were, in most target directions, accompanied by increases in the smoothness of the movement trajectories. When target acquisition required movement in both dfs, there were also practice-related decreases in the extent to which the trajectories deviated from a direct path to the target. The contribution of monofunctional muscles ( those producing torque in a single df) increased with practice during movements in which they acted as agonists. The activity in bifunctional muscles ( those contributing torque in both dfs) remained at pretest levels in most movements. The results suggest that performance gains were mediated primarily by changes in the spatial organization of muscles synergies. These changes were expressed most prominently in terms of the magnitude of activation of the monofunctional muscles.

The sites of neural adaptation induced by resistance training in humans

Although it has long been supposed that resistance training causes adaptive changes in the CNS, the sites and nature of these adaptations have not previously been identified. In order to determine whether the neural adaptations to resistance training occur to a greater extent at cortical or subcortical sites in the CNS, we compared the effects of resistance training on the electromyographic (EMG) responses to transcranial magnetic (TMS) and electrical (TES) stimulation. Motor evoked potentials (MEPs) were recorded from the first dorsal interosseous muscle of 16 individuals before and after 4 weeks of resistance training for the index finger abductors (n=8), or training involving finger abduction-adduction without external resistance (n=8). TMS was delivered at rest at intensities from 5% below the passive threshold to the maximal output of the stimulator. TMS and TES were also delivered at the active threshold intensity while the participants exerted torques ranging from 5 to 60% of their maximum voluntary contraction (MVC) torque. The average latency of MEPs elicited by TES was significantly shorter than that of TMS MEPs (TES latency=21.5+/-1.4 ms; TMS latency=23.4+/-1.4 ms; P

Adaptations of skeletal muscle pyruvate dehydrogenase kinase in response to food-restriction in mitochondrial subpopulations

University, 2006 Dr. Sandra J. Peters Pyruvate dehydrogenase (PDH) catalyses the decarboxylation of pyruvate, to form acetyl-CoA. PDH activity is down-regulated by intrinsic PDH kinases (predominantly PDK2 and PDK4 isoforms), but the understanding of the PDK isoform distribution and adaptation to nutritional stresses has been restricted to mixed mitochondrial populations, and not delineated between subsarcolemmal (SS) and intermyofibrillar (IMF) subpopulations. SS and IMF mitochondria exhibit distinct morphological and biochemical properties; however the functional differences are not well understood. This study investigated the effect of fed (FED) versus 48 h total foodrestriction (FR) on rat red gastrocnemius muscle PDK2 and 4 isoform content in SS and IMF mitochondria. PDK4 content was ~3-5 fold higher in SS mitochondria compared to IMF (p=0.001), and increased with FR -3-4- fold in both subpopulations (p<0.001). PDK2 was -2.5-4 fold higher in SS mitochondria compared to IMF (p=0.001), but PDK2 was unaltered with FR. Citrate synthase activity (|imol/min/mg mitochondrial protein) was not different between either subpopulation. As well there were no significant differences between mitochondrial subpopulations in PDH complex components in both fed and FR states. These results demonstrate that there is a markedly higher content of both PDK isofonns in SS compared to IMF mitochondria. Although PDK2 does not increase in either subpopulation in response to FR, PDK4 increases to a similar extent in both SS and IMF after 48 h food-restriction.

Myocyte remodeling in response to hypertrophic stimuli requires nucleocytoplasmic shuttling of muscle LIM protein

CSRP3 or muscle LIM protein (MLP) is a nucleocytoplasmic shuttling protein and a mechanosensor in cardiac myocytes. MLP regulation and function was studied in cultured neonatal rat myocytes treated with pharmacological or mechanical stimuli. Either verapamil or BDM decreased nuclear MLP while phenylephrine and cyclic strain increased it. These results suggest that myocyte contractility regulates MLP subcellular localization. When RNA polymerase II was inhibited with alpha-amanitin, nuclear MLP was reduced by 30%. However, when both RNA polymerase I and II were inhibited with actinomycin D, there was a 90% decrease in nuclear MLP suggesting that its nuclear translocation is regulated by both nuclear and nucleolar transcriptional activity. Using cell permeable synthetic peptides containing the putative nuclear localization signal (NLS) of MLP, nuclear import of the protein in cultured rat neonatal myocytes was inhibited. The NLS of MLP also localizes to the nucleolus. Inhibition of nuclear translocation prevented the increased protein accumulation in response to phenylephrine. Furthermore, cyclic strain of myocytes after prior NLS treatment to remove nuclear MLP resulted in disarrayed sarcomeres. Increased protein synthesis and brain natriuretic peptide expression were also prevented suggesting that MLP is required for remodeling of the myo filaments and gene expression. These findings suggest that nucleocytoplasmic shuttling MLP plays an important role in the regulation of the myocyte remodeling and hypertrophy and is required for adaptation to hypertrophic stimuli. (C) 2009 Elsevier Inc. All rights reserved.

Symmorphosis through dietary regulation: a combinatorial role for proteolysis, autophagy and protein synthesis in normalising muscle metabolism and function of hypertrophic mice after acute starvation

Animals are imbued with adaptive mechanisms spanning from the tissue/organ to the cellular scale which insure that processes of homeostasis are preserved in the landscape of size change. However we and others have postulated that the degree of adaptation is limited and that once outside the normal levels of size fluctuations, cells and tissues function in an aberant manner. In this study we examine the function of muscle in the myostatin null mouse which is an excellent model for hypertrophy beyond levels of normal growth and consequeces of acute starvation to restore mass. We show that muscle growth is sustained through protein synthesis driven by Serum/Glucocorticoid Kinase 1 (SGK1) rather than Akt1. Furthermore our metabonomic profiling of hypertrophic muscle shows that carbon from nutrient sources is being channelled for the production of biomass rather than ATP production. However the muscle displays elevated levels of autophagy and decreased levels of muscle tension. We demonstrate the myostatin null muscle is acutely sensitive to changes in diet and activates both the proteolytic and autophagy programmes and shutting down protein synthesis more extensively than is the case for wild-types. Poignantly we show that acute starvation which is detrimental to wild-type animals is beneficial in terms of metabolism and muscle function in the myostatin null mice by normalising tension production.