Muscle fibers are multinucleated, and muscle fiber nuclei (myonuclei) are believed to be post-mitotic and are typically situated near the periphery of the myofiber. Due to the unique organization of muscle fibers and their nuclei, the cellular and molecular mechanisms regulating myofiber homeostasis in unstressed and stressed conditions (e.g., exercise) are unique. A key role myonuclei play in regulating muscle during exercise is gene transcription. Only recently have investigators had the capability to identify molecular changes at high resolution exclusively in myonuclei in response to perturbations in vivo. The purpose of this review is to describe how myonuclei modulate their transcriptome, epigenetic status, mobility and shape, and microRNA expression in response to exercise in vivo. Given the relative paucity of high-fidelity information on myonucleus-specific contributions to exercise adaptation, we identify specific gaps in knowledge and provide perspectives on future directions of research.
Skeletal muscle anabolism is driven by numerous stimuli such as growth factors, nutrients (i.e., amino acids, glucose), and mechanical stress. These stimuli are integrated by the mechanistic target of rapamycin (mTOR) complex 1 (mTORC1) signal transduction cascade. In recent years, work from our laboratory and elsewhere has sought to unravel the molecular mechanisms underpinning the mTOR-related activation of muscle protein synthesis (MPS), as well as the spatial regulation of these mechanisms within the skeletal muscle cell. These studies have suggested that the skeletal muscle fiber periphery is a region of central importance in anabolism (i.e., growth/MPS). Indeed, the fiber periphery is replete with the substrates, molecular machinery, and translational apparatus necessary to facilitate MPS. This review provides a summary of the mechanisms underpinning the mTOR-associated activation of MPS from cell, rodent, and human studies. It also presents an overview of the spatial regulation of mTORC1 in response to anabolic stimuli and outlines the factors that distinguish the periphery of the cell as a highly notable region of skeletal muscle for the induction of MPS. Future research should seek to further explore the nutrient-induced activation of mTORC1 at the periphery of skeletal muscle fibers.
High-intensity and sprint interval training (HIIT and SIT, respectively) enhance insulin sensitivity and glycemic control in both healthy adults and those with cardiometabolic diseases. The beneficial effects of intense interval training on glycemic control include both improvements seen in the hours to days following a single session of HIIT/SIT and those which accrue with chronic training. Skeletal muscle is the largest site of insulin-stimulated glucose uptake and plays an integral role in the beneficial effects of exercise on glycemic control. Here we summarize the skeletal muscle responses that contribute to improved glycemic control during and following a single session of interval exercise and evaluate the relationship between skeletal muscle remodelling and improved insulin sensitivity following HIIT/SIT training interventions. Recent evidence suggests that targeting skeletal muscle mechanisms via nutritional interventions around exercise, particularly with carbohydrate manipulation, can enhance the acute glycemic benefits of HIIT. There is also some evidence of sex-based differences in the glycemic benefits of intense interval exercise, with blunted responses observed after training in females relative to males. Differences in skeletal muscle metabolism between males and females may contribute to sex differences in insulin sensitivity following HIIT/SIT, but well-controlled studies evaluating purported muscle mechanisms alongside measurement of insulin sensitivity are needed. Given the greater representation of males in muscle physiology literature, there is also a need for more research involving female-only cohorts to enhance our basic understanding of how intense interval training influences muscle insulin sensitivity in females across the lifespan.
Initially it was believed that phosphorylase was responsible for both glycogen breakdown and synthesis in the living cell. The discovery of glycogen synthase and McArdle's disease (lack of phosphorylase activity), together with the high Pi/glucose 1-P ratio in skeletal muscle, demonstrated that glycogen synthesis could not be attributed to reversal of the phosphorylase reaction. Rather, glycogen synthesis was attributable solely to the activity of glycogen synthase, subsequent to the transport of glucose into the cell. However, the well-established observation that phosphorylase was inactivated (i.e., dephosphorylated) during the initial recovery period after prior exercise, when the rate of glycogen accumulation is highest and independent of insulin, suggested that phosphorylase could play an active role in glycogen accumulation. But the quantitative contribution of phosphorylase inactivation was not established until recently, when studying isolated murine muscle preparations during recovery from repeated contractions at temperatures ranging from 25 to 35 °C. Thus, in both slow-twitch, oxidative and fast-twitch, glycolytic muscles, inactivation of phosphorylase accounted for 45%-75% of glycogen accumulation during the initial hours of recovery following repeated contractions. Such data indicate that phosphorylase inactivation may be the most important mechanism for glycogen accumulation under defined conditions. These results support the initial belief that phosphorylase plays a quantitative role in glycogen formation in the living cell. However, the mechanism is not via activation of phosphorylase, but rather via inactivation of the enzyme.
Adiponectin has been demonstrated to be a mediator of insulin sensitivity; however, the underlined mechanisms remain unclear. SESN2 is a stress-inducible protein that phosphorylates AMPK in different tissues. In this study, we aimed to validate the amelioration of insulin resistance by globular adiponectin (gAd) and to reveal the role of SESN2 in the improvement of glucose metabolism by gAd. We used a high-fat diet-induced wild-type and SESN2−/− C57BL/6J insulin resistance mice model to study the effects of six-week aerobic exercise or gAd administration on insulin resistance. In vitro study, C2C12 myotubes were used to determine the potential mechanism by overexpressing or inhibiting SESN2. Similar to exercise, six-week gAd administration decreased fasting glucose, triglyceride and insulin levels, reduced lipid deposition in skeletal muscle and reversed whole-body insulin resistance in mice fed on a high-fat diet. Moreover, gAd enhanced skeletal muscle glucose uptake by activating insulin signaling. However, these effects were diminished in SESN2−/− mice. We found that gAd administration increased the expression of SESN2 and Liver kinase B1 (LKB1) and increased AMPK-T172 phosphorylation in skeletal muscle of wild-type mice, while in SESN2−/− mice, LKB1 expression was also increased but the pAMPK-T172 was unchanged. At the cellular level, gAd increased cellular SESN2 and pAMPK-T172 expression. Immunoprecipitation experiment suggested that SESN2 promoted the formation of complexes of AMPK and LKB1 and hence phosphorylated AMPK. In conclusion, our results revealed that SESN2 played a critical role in gAd-induced AMPK phosphorylation, activation of insulin signaling and skeletal muscle insulin sensitization in mice with insulin resistance.
This study examined electromyographic amplitude (EMGRMS)-force relationships during repeated submaximal knee extensor muscle actions among chronic aerobically-(AT), resistance-trained (RT), and sedentary (SED) individuals. Fifteen adults (5/group) attempted 20 isometric trapezoidal muscle actions at 50% of maximal strength. Surface electromyography (EMG) was recorded from vastus lateralis (VL) during the muscle actions. For the first and last successfully completed contractions, linear regression models were fit to the log-transformed EMGRMS-force relationships during the linearly increasing and decreasing segments, and the b terms (slope) and a terms (antilog of y-intercept) were calculated. EMGRMS was averaged during steady force. Only the AT completed all 20 muscle actions. During the first contraction, the b terms for RT (1.301 ± 0.197) were greater than AT (0.910 ± 0.123; p = 0.008) and SED (0.912 ± 0.162; p = 0.008) during the linearly increasing segment, and in comparison to the linearly decreasing segment (1.018 ± 0.139; p = 0.014), respectively. For the last contraction, the b terms for RT were greater than AT during the linearly increasing (RT = 1.373 ± 0.353; AT = 0.883 ± 0.129; p = 0.018) and decreasing (RT = 1.526 ± 0.328; AT = 0.970 ± 0.223; p = 0.010) segments. In addition, the b terms for SED increased from the linearly increasing (0.968 ± 0.144) to decreasing segment (1.268 ± 0.126; p = 0.015). There were no training, segment, or contraction differences for the a terms. EMGRMS during steady force increased from the first- ([64.08 ± 51.68] μV) to last-contraction ([86.73 ± 49.55] μV; p = 0.001) collapsed across training statuses. The b terms differentiated the rate of change for EMGRMS with increments in force among training groups, indicating greater muscle excitation to the motoneuron pool was necessary for the RT than AT during the linearly increasing and decreasing segments of a repetitive task.
Exercise is an effective strategy to prevent and improve obesity and related metabolic diseases. Exercise increases the metabolic demand in the body. Although many of the metabolic health benefits of exercise depend on skeletal muscle adaptations, exercise exerts many of its metabolic effects through the liver, adipose tissue, and pancreas. Therefore, exercise is the physiological state in which inter-organ signaling is most important. By contrast, circadian rhythms in mammals are associated with the regulation of several physiological and biological functions, including body temperature, sleep-wake cycle, physical activity, hormone secretion, and metabolism, which are controlled by clock genes. Glucose and lipid tolerance reportedly exhibit diurnal variations, being lower in the evening than in the morning. Therefore, the effects of exercise on substrate metabolism at different times of the day may differ. In this review, the importance of exercise timing considerations will be outlined, incorporating a chrono-exercise perspective.
To determine whether existing exercise therapies can restore the joint position sense (JPS) deficits of patients with chronic ankle instability (CAI) when compared with controlled non-training patients. Seven databases were searched using ankle, injury, proprioception, and exercise-therapy-related terms. Peer-reviewed human studies in English that used the absolute errors score of joint position reproduction (JPR) test to compare the JPS of injured ankles in CAI patients before and after exercise therapy and non-training controls were included and analyzed. Demographic information, sample size, description of exercise therapies, methodological details of the JPR test, and absolute error scores were extracted by two researchers independently. Meta-analysis of the differences in JPS changes (i.e., absolute errors after treatment minus the baseline) between the exercise therapies and non-training controls was performed with the weighted mean difference (WMD) and 95% confidence interval (CI). Seven studies were finally included. Meta-analyses revealed significantly higher improvements in passive JPS during inversion with, WMD = −1.54° and eversion, of, WMD = −1.80°, after exercise therapies when compared with non-training controls. However, no significant changes in the impaired side active JPS were observed with regard to inversion and eversion. Existing exercise therapies may have a positive effect on passive JPS during inversion and eversion, but do not restore the active JPS deficits of injured ankles in patients with CAI when compared with non-training controls. Updated exercise components with a longer duration that focus on active JPS with longer duration are needed to supplement the existing content of exercise therapies.
The effects of combined training (CT) on improving general health are well known, however, few studies have investigated the effects of low-volume CT. So, the aim of this study is to investigate the effects of 6 weeks of low-volume CT on body composition, handgrip strength (HGS), cardiorespiratory fitness (CRF) and affective response (AR) to exercise. Eighteen healthy, active young adult man (mean ± SD, [20.06 ± 1.66] years; [22.23 ± 2.76] kg/m2) performed either a low-volume CT (EG, n = 9), or maintained a normal life (CG, n = 9). The CT was composed of three resistance exercises followed by a high intensity-interval training (HIIT) on cycle ergometer performed twice a week. The measures of the body composition, HGS, maximal oxygen consumption (V˙O2max) and AR to exercise were taken at baseline and after training for analysis. Furthermore, an ANOVA test of repeated measures and t-test paired samples were used with a p ≤ 0.05. The results showed that EG improved HGS (pre: [45.67 ± 11.84] kg vs. post: [52.44 ± 11.90] kg, p < 0.01) and V˙O2max (pre: [41.36 ± 5.16] ml⋅kg-1⋅min-1 vs. post: [44.07 ± 5.98] ml⋅kg-1⋅min-1, p < 0.01). Although, for all measures the body composition had not significant differences between weeks (p > 0.05), nevertheless the feeling scale was positive in all weeks and without significant differences between them (p > 0.05). Lastly, for active young adults, the low-volume CT improved HGS, CRF and had a positive outcome in AR, with less volume and time spent than traditional exercise recommendations.
In a medical setting, such as the treatment of post-operative nosebleeds, nasal packing, including the use of nasal packs, nasal plugs or nasal tampons (NTs), is widely used to temporarily control anterior epistaxis. Although some literature has documented the use of NTs as a quick, easy and temporary solution to deal with anterior epistaxis in sports-induced nasal injuries, additional research is needed to appreciate on-field versus off-field efficacy, as well as the efficiency of different brands of NTs and packing materials.