Background: Menopause is associated with increases in visceral adipose tissue, reductions in lean mass, and a reduced energy expenditure. The ovariectomized (OVX) rat model can be used to model these changes and to test potential interventions that may attenuate this response. Red rooibos (RR), due to its high polyphenol content, may counter the effect of low estrogen concentrations. Objectives: To determine if consumption of RR can blunt the changes to body composition, metabolic outcomes, and movement that occur in the OVX rat model. Methods: Fifty-six female, 6-mo-old, Sprague-Dawley rats were randomly assigned to 4 groups (n = 14 per group): SHAM-WATER (sham surgery and consumed water without RR), SHAM-RR, OVX-WATER, and OVX-RR. RR (2.6 g RR per kilogram body mass) was provided ad libitum for 12 wk. At baseline and endpoint, body composition was measured using dual energy X-ray absorptiometry, and metabolic measures and movement were measured using a Promethion metabolic caging system. Results: RR did not attenuate OVX-induced changes. As expected, OVX resulted in a higher whole-body percent fat mass, a lower percent lean mass, and a higher body mass than SHAM rats (P < 0.05). At the endpoint, OVX rats had a higher ovarian adipose tissue mass and inguinal adipose tissue mass (P < 0.05) with a trend for reduced brown adipose tissue mass than SHAM rats (P = 0.072). There were no differences between groups for metabolic measures (energy expenditure, gas exchange). OVX rats also had a trend of a long lounge time (P = 0.065) and total lounge time (P = 0.070) compared with SHAM. Conclusions: RR intervention did not attenuate the changes to body composition, metabolic, or movement outcomes observed in the OVX group. This study provides insights into the progression of body composition and metabolic changes in the OVX rat model, contributing to a better understanding of the physiological impacts of estrogen deficiency.

OBJECTIVES:To describe injury and illness rates, locations, mechanisms, and types among ringette athletes competing at the Canada Games. DESIGN:Retrospective cohort study. METHODS:This retrospective cohort analyzed ringette injury and illness data from the 2011, 2015, and 2019 Canada Games. Athlete registrations and medical reports from the Games were reviewed and classified using the 2020 International Olympic Committee consensus statement on methods for recording and reporting epidemiological data on injury and illness in sport and the 2020 consensus version of the Orchard Sports Injury and Illness Classification System. This study focused on injuries directly related to participation in ringette where athletes sought medical attention. Incidence rates (injuries per 1000 athlete-days) with 95% confidence intervals were estimated using Poisson regression offset by athlete-days, accounting for clustering by contingent (province/territory). Illness incidence rates and confidence intervals were estimated using confidence means based on normal distributions. RESULTS:In total, there were 174 injuries, of which, 123 were sport-related over 3199 athlete-days. There were 23 illnesses among ringette athletes. The injury incidence rate was 38.45 (95% confidence interval: 29.52-50.08) per 1000 athlete-days and the illness incidence rate was 7.19 (95% confidence interval: 4.56-10.79) per 1000 athlete-days. Contact mechanisms caused 40.65% of injuries, followed by gradual onset (37.40%). Respiratory illnesses were most frequent (60.87%). CONCLUSIONS:Despite ringette's non-contact rules, contact injuries were common along with overuse injuries and respiratory illnesses. Targeted prevention strategies through protective equipment, training modifications, and respiratory health monitoring may reduce risk and support athlete welfare in this growing sport.

BACKGROUND:Protein intake during adolescence may influence bone development and immune status, yet the comparative effects of wholefood protein sources compared with protein isolates in adolescent athletes remain unclear. OBJECTIVES:To compare the effects of Greek yogurt (GY) and whey protein (WP) supplementation on bone and inflammation markers in adolescent athletes throughout a competitive season. METHODS:Athletes completed an initial control period on their habitual diets (weeks 0‒8), followed by randomization to GY (n = 24; 15.8 ± 1.1 y; 11 females) or WP (n = 23; 16.0 ± 1.4 y; 10 females) for a 16-wk intervention (weeks 8‒24). GY consumed 2 servings per day of 175 g GY (17 g protein); WP received an isonitrogenous WP supplement. Blood samples and body composition assessments were obtained at weeks 0, 8, 16, and 24. RESULTS:Procollagen type I N-terminal propeptide, insulin-like growth factor-1, and receptor activator of nuclear factor κB ligand remained stable. Osteocalcin and osteoprotegerin showed sex-specific between-group differences: osteocalcin declined throughout weeks 0‒24 in GY males, whereas osteoprotegerin declined during weeks 0‒16 in GY females and was elevated at the end of the control period in WP females. C-terminal telopeptide of type I collagen and sclerostin showed intervention group-dependent, but not sex-dependent, differences. C-terminal telopeptide of type I collagen increased transiently from week 8 to week 16 and returned to baseline by week 24 only in GY. Sclerostin concentrations fluctuated, and at 24 wk, were not different from baseline in GY but were higher than baseline in WP. At week 16, interleukin (IL)-1β increased in WP, and IL-6 decreased in GY. IL-10 and tumor necrosis factor α increased during the control period and decreased with WP only in females. CONCLUSIONS:Increased protein intake, independent of source, was associated with modest, often sex-specific fluctuations in bone and inflammatory markers in adolescent athletes, potentially influenced by growth and training-related factors across the competitive season. This trial was registered at clinicaltrials.gov as NCT05922462.

BACKGROUND/OBJECTIVES:This 8-week randomized pilot intervention trial examined the effects of Greek yogurt (GY) supplementation on markers of bone turnover and inflammation in older adult exercisers. METHODS:A total of 48 participants aged 55+ completed this 8-week intervention: 33 exercisers randomized to exercisers receiving GY (GYEX, n = 18, 12 females) and exercisers without GY (NYEX, n = 15, 12 females), and a group of 15 age-matched, community-dwelling, non-exercisers also receiving GY (GYNE, n = 15, 10 females). Exercisers were enrolled in a moderate-intensity community-based exercise program. GYEX and GYNE supplemented their diet with two daily servings of 175 g of GY (17 g protein, 225 mg calcium per serving). Assessments at baseline and week 8 included dietary intake, body composition, and fasting blood samples for bone markers and pro-inflammatory cytokines. RESULTS:Body mass increased modestly across groups (time effect, p = 0.033), with no changes in body fat. C-terminal telopeptide of type I collagen (bone resorption marker) increased 14% in GYEX (time × group interaction, p = 0.022). Osteoprotegerin (bone formation regulator) decreased overall by 4% (time effect, p = 0.002). Dickkopf-1 (bone formation inhibitor) increased by 13% (p = 0.008) in GYNE but not in exercisers (time × group interaction, p = 0.018). Interleukin 1β and interleukin 6 showed significant interactions (p = 0.043 and p = 0.023), where interleukin 1β increased by 80% (p = 0.007) and interleukin 6 decreased by 89% (p < 0.001) in GYNE, but remained stable in exercisers. Tumor necrosis factor alpha remained unchanged. CONCLUSIONS:Although the observed effects of GY on the assessed biomarkers were limited and should be interpreted cautiously due to pilot design and statistical constraints, they highlight the need for longer interventions to determine whether whole-food dairy proteins can meaningfully support skeletal and immune health in older adults.

This study, in vivo and in vitro, investigated the role of brain-derived neurotrophic factor (BDNF) in skeletal muscle adaptations to aerobic exercise. BDNF is a contraction-induced protein that may play a role in muscle adaptations to aerobic exercise. BDNF is involved in muscle repair, increased fat oxidation, and mitochondrial biogenesis, all of which are adaptations observed with aerobic training. The purpose of this study was two-pronged and investigated the skeletal muscle BDNF response to (1) acute and (2) chronic exercise in male C57BL/6J mice. It also examined if chronic BDNF treatment resulted in similar adaptations to chronic exercise. In aim 1, mice underwent a 2 hr. treadmill exercise bout. In aim 2, mice were assigned to one of four groups: (1) control (CON); (2) endurance training (ET; treadmill running 1 h/day, 5 days/wk); (3) BDNF (BDNF; 0.5 mg/kgbw, 5 days/wk); (4) endurance training and BDNF (ET + BDNF) for 8 weeks. Results demonstrated that the soleus (SOL) had higher BDNF content compared with the extensor digitorum longus (EDL) and that SOL BDNF increased with acute exercise. After chronic exercise and BDNF treatment, treadmill testing to exhaustion demonstrated a main effect of BDNF and ET on increasing exercise capacity. In vitro contractile assessment of the EDL revealed BDNF treatment resulted in similar increases in the max rate of relaxation as ET. EDL force-frequency analysis showed ET + BDNF produced higher force than CON and BDNF, indicating an additive effect. BDNF increased EDL mitochondrial proteins, COXIV, and CS. These results demonstrate that BDNF contributes to muscle adaptations observed with ET.

Here we show that partial GSK3 knockdown has minimal effects on whole body metabolism and muscle contractility in female mice. This is partly inconsistent with previous results found in male mice, which reveal a potential influence of biological sex.

Inhibiting glycogen synthase kinase 3 (GSK3) improves muscle function, metabolism, and bone health in many diseases and conditions; however, whether GSK3 should be targeted for Duchenne muscular dystrophy (DMD), a severe muscle wasting disorder with no cure, remains unknown. Here, we show the effects of GSK3 inhibition in male DBA/2J (D2) and C57BL/10 (C57) mdx mice. Treating D2 mdx mice with GSK3 inhibitors alone or in combination with aerobic exercise improves muscle strength, endurance, and morphology, attenuates the hypermetabolic phenotype, and enhances insulin sensitivity. GSK3 inhibition in C57 mdx mice also improves muscle fatigue resistance and increases cage ambulation. Moreover, muscle-specific GSK3 knockdown in mdx mice augments muscle force production and endurance. In both mdx strains, GSK3 inhibition increases bone mineral content and density. Overall, these improvements to muscle, metabolic, and bone health with GSK3 inhibition in mdx mice may have clinical implications for patients with DMD, where the current standard of care, glucocorticoids, delay the loss of ambulation but increase the risk for insulin resistance and osteoporosis. Along with our observation of lowered beta-catenin content in DMD myoblasts, a known cellular target for GSK3, this study provides ample evidence in support of inhibiting GSK3 for this disease. Inhibiting glycogen synthase kinase 3 (GSK3) improves muscle function, metabolism, and bone health in many other diseases. Here, Marcella et al. found that inhibiting glycogen synthase kinase 3, alone or combined with exercise, improves muscle health and function in mouse models of Duchenne muscular dystrophy without negatively affecting insulin sensitivity or bone health.

Nutraceutical approaches to promote adipose tissue thermogenesis may help to prevent obesity onset. Creatine is a critical regulator of adipose metabolic function and low-dose lithium supplementation has been shown to promote adipose thermogenesis. In the present study, we sought to directly compare the two supplements for their effects on adipose metabolism and thermogenesis. We show that both supplements increase daily energy expenditure (EE) and reduce body mass in male Sprague-Dawley rats. Lithium increased brown adipose tissue (BAT) mitochondrial and lipolytic proteins that are associated with thermogenesis, while creatine increased BAT UCP1 and mitochondrial respiration. The BAT thermogenic findings were not observed in females. White adipose tissue and skeletal muscle markers of thermogenesis were unaltered with the supplements. Together, the data show that low-dose lithium and creatine have diverging effects on markers of BAT thermogenesis and that each increase daily EE and lower body mass in a sex-dependent manner.

The purpose of this investigation was to determine whether off-ice key performance indicators (KPIs) of linear skating speed are global across all skaters or modulated based on relevant cohort-dependent covariates. A total of 112 development- and university-level hockey players completed on-ice (30-m skate; ICE 0-30 m) and off-ice assessments (30-m sprint with split times, countermovement jump; CMJ, broad jump, and maximum chin ups). A linear regression model was created to predict ICE 0-30 m times from off-ice inputs with height, body mass, age level, and strength level included as covariates. Model parameters were estimated using the LASSO method with k-fold cross validation. The final model had a cross-validated R2 of 0.806. The strongest predictor of ICE 0-30 m times was 20-30 m sprint time (ss = 0.088). Relative propulsive mean power (ss = -0.064) from the CMJ, 0-30 m sprint time (ss = 0.058), and broad jump (ss = -0.046) represented second-tier predictors. Both relative braking net impulse (ss = 0.043) and relative braking mean power (ss = -0.009) from the CMJ were predictive factors for lower strength players only. The results indicate that top speed sprinting represents the primary global KPI and closest off-ice proxy for skating speed regardless of cohort.

This study examined changes in body mass and body mass index (BMI), physical activity, and dietary intake in Canadian university students during the first year of the COVID-19 pandemic. Two self-reported recall surveys were conducted: after the first lockdown in September 2020 (T1) and following the second lockdown in March 2021 (T2). Eligible participants were full-time undergraduate students attending a Canadian university and residing in Canada during the first year of the pandemic. At T1, 510 students (99 male, 411 female) completed the survey, and of those, 135 (32 males, 103 females) completed the survey at T2 (73% attrition). At both T1 and T2, most participants were 18-24 years of age (93% and 90%, respectively), Caucasian (73% and 78%, respectively), and resided in the province of Ontario (79% and 80%, respectively). Body mass increased from T1 to T2 (+0.91 ± 3.89 kg t(132) = -2.7, p = 0.008). BMI also increased from T1 to T2 (+0.30 ± 1.33 kg/m2 [t(130) = -2.5, p = 0.012), with a greater number of participants within the overweight range (19.8% versus 24.4%, respectively). At T1, 38% of the participants reported a decrease in physical activity, while the number of students reporting a decrease in activity increased to 56% at T2. Dietary energy intake decreased from 1678 ± 958 kcal/day at T1 to 1565 ± 842 kcal/day at T2 [c2(1) = 7.2, p = 0.007]. Diet quality also decreased, with participants not meeting the recommended daily allowance for essential macro and micronutrients. A decrease was observed in daily servings of fruits (-27%, p < 0.001), vegetables (-72%, p < 0.001), and grains (-68%, p < 0.001). In conclusion, despite a small decrease in dietary energy intake, a modest weight gain occurred during the first year of the COVID-19 pandemic in this cohort of Canadian university students, which was potentially related to decreased physical activity and diet quality.

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Background: Glycogen synthase kinase 3 (GSK3) is a constitutively active serine/threonine protein kinase. Originally identified in skeletal muscle for its role in glucose homeostasis, GSK3 also negatively regulates muscle size and the transcription of genes associated with the oxidative phenotype. Previous studies have found that GSK3 inhibition improves whole-body metabolism and muscle quality in male mice. However, many physiological dissimilarities between male and female mice have been observed, specifically in terms of metabolic regulation; and it is currently unknown as to whether the effects of GSK3 inhibition observed in male mice are reproducible in female mice. Therefore, this study examined the effects of a muscle-specific GSK3 reduction on whole-body metabolism and muscle force production in female mice. We hypothesized that the muscle-specific reduction of GSK3 would improve glucose tolerance and muscle force production in female mice. Methods: A skeletal-muscle specific GSK3 partial (~50%) knockdown model (GSK3mKD) was generated on a C57BL/6J background. Experiments were conducted on female mice aged 2-4 months, with flox littermates (GSK3floxed) serving as controls (n = 6 per group). During the 7-week intervention, dual-energy X-ray absorptiometry (DXA) scans were completed at baseline and week 7. On weeks 5 and 7, mice were housed in a Promethion metabolic cage system for 48hours. Glucose and insulin tolerance tests (GTT, ITT) were completed on week 6. At time of euthanasia, soleus (SOL) and extensor digitorum longus (EDL) muscles were dissected and subjected to isolated skeletal muscle force frequency contractile experiments. Results: There was a main effect of body mass demonstrating that GSK3mKD mice were heavier than GSK3flox mice due to an increase in fat mass ( p = 0.02) and a trending increase in lean mass ( p = 0.08). There were no differences in cage activity, food intake, daily energy expenditure (DEE), respiratory exchange ratio, glucose- or insulin tolerance. There was a significant increase in force production in the EDL ( p = 0.005), which we attribute to a trending increase in cross-sectional area ( p = 0.08). In contrast, there were no differences in force production in the SOL. Conclusion: This study found that the muscle-specific partial knockdown of GSK3 increased body mass, but did not alter the metabolic phenotype (i.e., DEE or whole-body glucose regulation) in female mice, which is in contrast with GSK3 inhibition studies previously conducted in male mice. Furthermore, force production only increased in the EDL, which was primarily due to an increase in muscle size. In conclusion, there appears to be differences in the response to GSK3 inhibition in male and female mice, and future studies in our lab will examine the potential cellular mechanisms. CIHR Canada Research Chairs Program This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorder. Due to its narrow therapeutic window (0.5-1.2 mM serum concentration), there is a stigma associated with lithium treatment and the adverse effects that can occur at therapeutic doses. However, several studies have indicated that doses of lithium under the predetermined therapeutic dose used in bipolar disorder treatment may have beneficial effects not only in the brain but across the body. Currently, literature shows that low-dose lithium (≤0.5 mM) may be beneficial for cardiovascular, musculoskeletal, metabolic, and cognitive function, as well as inflammatory and antioxidant processes of the aging body. There is also some evidence of low-dose lithium exerting a similar and sometimes synergistic effect on these systems. This review summarizes these findings with a focus on low-dose lithium’s potential benefits on the aging process and age-related diseases of these systems, such as cardiovascular disease, osteoporosis, sarcopenia, obesity and type 2 diabetes, Alzheimer’s disease, and the chronic low-grade inflammatory state known as inflammaging. Although lithium’s actions have been widely studied in the brain, the study of the potential benefits of lithium, particularly at a low dose, is still relatively novel. Therefore, this review aims to provide possible mechanistic insights for future research in this field.

Background: Lithium, a commonly used treatment for bipolar disorder, has been shown to have neuroprotective effects for other conditions including Alzheimer's disease via the inhibition of the enzyme glycogen synthase kinase-3 (GSK3). However, dose-dependent adverse effects of lithium are well-documented, highlighting the need to determine if low doses of lithium can reliably reduce GSK3 activity. Objective: The purpose of this study was to evaluate the effects of a low-dose lithium supplementation on GSK3 activity in the brain of an early, diet-induced Alzheimer's disease model. Methods: Male C57BL/6J mice were divided into either a 6-week or 12-week study. In the 6-week study, mice were fed a chow diet or a chow diet with lithium-supplemented drinking water (10 mg/kg/day) for 6 weeks. Alternatively, in the 12-week study, mice were fed a chow diet, a high-fat diet (HFD), or a HFD with lithium-supplemented drinking water for 12 weeks. Prefrontal cortex and hippocampal tissues were collected for analysis. Results: Results demonstrated reduced GSK3 activity in the prefrontal cortex as early as 6 weeks of lithium supplementation, in the absence of inhibitory phosphorylation changes. Further, lithium supplementation in an obese model reduced prefrontal cortex GSK3 activity as well as improved insulin sensitivity. Conclusion: Collectively, these data provide evidence for low-dose lithium supplementation to inhibit GSK3 activity in the brain. Moreover, these results indicate that GSK3 activity can be inhibited despite any changes in phosphorylation. These findings contribute to an overall greater understanding of low-dose lithium's ability to influence GSK3 activity in the brain and its potential as an Alzheimer's disease prophylactic.

Milk and dairy products with their distinct composition of carbohydrates, proteins, fats, and micronutrients are purported to have beneficial effects on human health. They have the potential to enhance exercise performance and recovery and are considered functional sport foods/beverages. This chapter summarizes the current evidence regarding the benefits of dairy products on endurance and resistance exercise, as well as the potential to augment health and performance in a variety of populations including team sport athletes, exercising children and adolescents, and aging adults. The impact of dairy products on weight loss and sleep quality is also discussed.

Duchenne muscular dystrophy (DMD) is a severe muscle wasting disorder that leads to early mortality. We examined the pathogenic contribution of glycogen synthase kinase 3 (GSK3) to DMD using the mdx model. GSK3 is a serine/threonine kinase that has been implicated in other muscular dystrophies and our initial results showed that overactivation of GSK3 may contribute to increased disease severity found in DBA/2J (D2) mdx mice vs C57BL/10 mdx mice. In support of this, treating D2 mdx mice with the GSK3 inhibitor, tideglusib (10 mg/kg/day), increased muscle mass, strength, and fatigue resistance. We also found elevated proportions of oxidative fibers and increased utrophin mRNA, while muscle necrosis and oxidative stress were reduced. Finally, young D2 mdx mice displayed early diastolic dysfunction, and this was blunted with tideglusib treatment – an effect attributed to lowered oxidative stress and fibrosis. This study highlights the therapeutic potential of tideglusib and GSK3 inhibition for DMD.

While the vast majority of research involving creatine supplementation has focused on skeletal muscle, there is a small body of accumulating research that has focused on creatine and the brain. Preliminary studies indicate that creatine supplementation (and guanidinoacetic acid; GAA) has the ability to increase brain creatine content in humans. Furthermore, creatine has shown some promise for attenuating symptoms of concussion, mild traumatic brain injury and depression but its effect on neurodegenerative diseases appears to be lacking. The purpose of this narrative review is to summarize the current body of research pertaining to creatine supplementation on total creatine and phophorylcreatine (PCr) content, explore GAA as an alternative or adjunct to creatine supplementation on brain creatine uptake, assess the impact of creatine on cognition with a focus on sleep deprivation, discuss the effects of creatine supplementation on a variety of neurological and mental health conditions, and outline recent advances on creatine supplementation as a neuroprotective supplement following traumatic brain injury or concussion.

It is well-established that creatine supplementation augments the gains in muscle mass and performance during periods of resistance training. However, whether the timing of creatine ingestion influences these physical and physiological adaptations is unclear. Muscle contractions increase blood flow and possibly creatine transport kinetics which has led some to speculate that creatine in close proximity to resistance training sessions may lead to superior improvements in muscle mass and performance. Furthermore, creatine co-ingested with carbohydrates or a mixture of carbohydrates and protein that alter insulin enhance creatine uptake. The purpose of this narrative review is to (i) discuss the purported mechanisms and variables that possibly justify creatine timing strategies, (ii) to critically evaluate research examining the strategic ingestion of creatine during a resistance training program, and (iii) provide future research directions pertaining to creatine timing.

The authors of “Effects of Post-Exercise Whey Protein Consumption on Recovery Indices in Adolescent Swimmers” report an error in Table 1 of their article [...]

Introductory paragraphDuchenne muscular dystrophy (DMD) is a severe X-linked muscle wasting disorder that affects 1 in 5,000 males worldwide1. It is caused by the absence of functional dystrophin, which compromises muscle integrity, leading to progressive muscle wasting and weakness2. Glucocorticoids are the standard of care for patients with DMD as they delay the loss of ambulation by an average of 3 years3; however, they are also associated with adverse effects such as insulin resistance and increased risk of type 2 diabetes4. Thus, alternative therapeutic options should be explored. Here, we show that treating the DBA/2Jmdxmouse with the glycogen synthase kinase 3 (GSK3) inhibitor, tideglusib, improved skeletal muscle function and insulin sensitivity, while also attenuating the hypermetabolic phenotype previously observed in these mice5. Furthermore, treatingmdxmice with the GSK3 inhibitor, lithium, augmented the benefits of voluntary wheel running on insulin sensitivity and skeletal muscle function despite running half of the total distance compared to control-treatedmdxmice. This is important given that some patients with DMD may not be able to engage in adequate amounts of physical activity. Thus, GSK3 inhibition alone or in combination with exercise can enhance skeletal muscle function and insulin sensitivity inmdxmice.