When muscle biopsies first began to be used routinely in research on exercise physiology five decades ago, it soon become clear that the muscle content of glycogen is an important determinant of exercise performance. r Glycogen particles are stored in distinct pools within the muscles, but the role of each pool during exercise and how this is affected by diet is unknown. r Here, the effects of diet and exercise on these pools, as well as their relation to endurance during prolonged cycling were examined. r We demonstrate here that an improved endurance capacity with high carbohydrate loading is associated with a temporal shift in the utilisation of the distinct stores of glycogen pools and is closely linked to the content of the glycogen pool closest to actin and myosin (intramyofibrillar glycogen). r These findings highlight the functional importance of distinguishing between different subcellular microcompartments of glycogen in individual muscle fibres.

Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation.

The effects of short-term high-intensity exercise on single fiber contractile function in humans are unknown. Therefore, the purposes of this study were: (a) to access the acute effects of repeated high-intensity exercise on human single muscle fiber contractile function; and (b) to examine whether contractile function was affected by alterations in the redox balance. Eleven elite cross-country skiers performed four maximal bouts of 1300 m treadmill skiing with 45 min recovery. Contractile function of chemically skinned single fibers from triceps brachii was examined before the first and following the fourth sprint with respect to Ca(2+) sensitivity and maximal Ca(2+) -activated force. To investigate the oxidative effects of exercise on single fiber contractile function, a subset of fibers was incubated with dithiothreitol (DTT) before analysis. Ca(2+) sensitivity was enhanced by exercise in both MHC I (17%, P < 0.05) and MHC II (15%, P < 0.05) fibers. This potentiation was not present after incubation of fibers with DTT. Specific force of both MHC I and MHC II fibers was unaffected by exercise. In conclusion, repeated high-intensity exercise increased Ca(2+) sensitivity in both MHC I and MHC II fibers. This effect was not observed in a reducing environment indicative of an exercise-induced oxidation of the human contractile apparatus.

Key pointsr Muscle glycogen content is associated with muscle function, but the physiological link between the two is poorly understood.r This study investigated the effects of inhibiting glycogenolysis, while maintaining high overall energy status, on different aspects of muscle function.r We demonstrate here that Na + ,K + -ATPase activity depends on glycogenolytically derived ATP regardless of high global ATP, with a decrease in activity leading to reduced force production and accelerated fatigue development.r The results support the concept of compartmentalized energy transfer with glycogen metabolism playing a crucial role in intramuscular ATP resynthesis and ion regulation.r This study gives specific insights into muscular function and may help towards a better understanding of glycogen storage diseases and muscle fatigue.Abstract Skeletal muscle glycogen content is associated with muscle function and fatigability. However, little is known about the physiological link between glycogen content and muscle function. Here we aimed to investigate the importance of glycogenolytically derived ATP per se on muscle force and action potential (AP) repriming period, i.e. the time before a second AP can be produced (indicative of Na + ,K + -ATPase activity). Single fibres from rat extensor digitorum longus muscles were isolated and mechanically skinned in order to investigate force production and the AP repriming period while global ATP and PCr concentrations were kept high. The importance of glycogenolytically derived ATP was studied by inhibition of glycogen phosphorylase (1,4-dideoxy-1,4-imino-D-arabinitol (DAB; 2 mM) or CP-316,819 (CP; 10 µM)) or glycogen removal (amyloglucosidase, 20 U ml −1 ). Tetanic force decreased by (mean (SD)) 21 (15)% (P < 0.001) and 76 (28)% (DAB) or 94 (6)% (CP, P < 0.001) in well-polarized Rasmus Jensen is a PhD Fellow at Department of Sports Science and Clinical Biomechanics, University of Southern Denmark, where he also obtained his master's degree. The initial experiments in the present study were initiated as part of his master thesis and convinced him to pursue a career in research. His primary interest is how muscle function and metabolism interact, and he is currently expanding his focus to include in vivo studies in humans and hopes to continue to combine in vivo and in vitro experiments in the future. and partially depolarized fibres, respectively. In depolarized fibres, twitch force decreased by 16 (10)% and 55 (26)% with DAB and CP, respectively, with no effect in well-polarized fibres (84 (10)%, P = 0.14). There was no effect of glycogen phosphorylase inhibition on repriming period in well-polarized fibres (median (25th, 75th percentile): 5 (4, 5) vs. 4 (4, 5) ms, P = 0.26), while the repriming period was prolonged from 6 (5, 7) to 8 (7, 10) ms (P = 0.01) in partially depolarized fibres. In line with this, glycogen removal increased repriming period from 5 (5, 6) to 6 (5, 7) ms (P = 0.003) in depolarized fibres. Together, these data strongly indicate that blocking glycogenoly...

Glycogen supercompensation after glycogen-depleting exercise can be achieved by consuming a carbohydrate-enriched diet, but the associated effects on the size, number and localization of intramuscular glycogen particles are unknown. We investigated how a glycogen-loading protocol affects fibre type-specific glycogen volume density, particle diameter and numerical density in three subcellular pools: between (intermyofibrillar) or within (intramyofibrillar) the myofibrils or beneath the sarcolemma (subsarcolemmal). Resting muscle biopsies from 11 physically active men were analysed using transmission electron microscopy after mixed (MIX), LOW or HIGH carbohydrate consumption separated by glycogen-lowering cycling at 75% of maximal oxygen consumption until exhaustion. After HIGH, the total volumetric glycogen content was 40% [95% confidence interval 16, 68] higher than after MIX in type I fibres (P < 0.001), with little to no difference in type II fibres (9% [95% confidence interval −9, 27]). Median particle diameter was 22.5 (interquartile range 20.8-24.7) nm across glycogen pools and fibre types, and the numerical density was 61% [25, 107] and 40% [9, 80] higher in the subsarcolemmal (P < 0.001) and intermyofibrillar (P < 0.01) pools of type I fibres, respectively, with little to no difference in the intramyofibrillar pool (3% [−20, 32]). In LOW, total glycogen was in the range of 21-23% lower, relative to MIX, in both fibre types, reflected in a 21-46% lower numerical density across pools. In comparison to MIX, particle diameter was unaffected by other diets ([−1.4, 1.3] nm). In conclusion, glycogen supercompensation after prolonged cycling is exclusive to type I fibres, predominantly in the subsarcolemmal pool, and involves an increase in the numerical density rather than the size of existing glycogen particles.