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Papers by Brian Roy

Biology

This study examined changes in body mass and body mass index (BMI), physical activity, and dietar... more 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), ...

Journal of the International Society of Sports Nutrition, 2022

Current Neuropharmacology, 2022

: Lithium is most well-known for its mood-stabilizing effects in the treatment of bipolar disorde... more : 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.

PLOS ONE, 2015

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International Journal of Environmental Research and Public Health

The authors of “Effects of Post-Exercise Whey Protein Consumption on Recovery Indices in Adolesce... more 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 [...]

Carolina Digital Repository (University of North Carolina at Chapel Hill), 2022

It is well-established that creatine supplementation augments the gains in muscle mass and perfor... more 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.

bioRxiv (Cold Spring Harbor Laboratory), Feb 16, 2022

The FASEB Journal, Apr 1, 2013

Journal of Biological Chemistry, Nov 1, 2022

Physiology, May 1, 2023

Background: Glycogen synthase kinase 3 (GSK3) is a constitutively active serine/threonine protein... more 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.

Children

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Journal of Alzheimer's Disease

Background: Lithium, a commonly used treatment for bipolar disorder, has been shown to have neuro... more 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 c...

Experimental Physiology, 2020

New Findings What is the central question of this study? Inhibition of glycogen synthase kinase‐3... more New Findings What is the central question of this study? Inhibition of glycogen synthase kinase‐3 (GSK3) has been shown to improve cardiac SERCA2a function. Lithium can inhibit GSK3, but therapeutic doses used in treating bipolar disorder can have toxic effects. It has not been determined whether subtherapeutic doses of lithium can improve cardiac SERCA function. What is the main finding and its importance? Using left ventricles from wild‐type mice, we found that subtherapeutic lithium feeding for 6 weeks decreased GSK3 activity and increased cardiac SERCA function compared with control‐fed mice. These findings warrant the investigation of low‐dose lithium feeding in preclinical models of cardiomyopathy and heart failure to determine the therapeutic benefit of GSK3 inhibition. The sarco(endo)plasmic reticulum Ca2+‐ATPase (SERCA) pump is responsible for regulating calcium (Ca2+) within myocytes, with SERCA2a being the dominant isoform in cardiomyocytes. Its inhibitor, phospholamban (...

SummaryThe DBA/2J (D2) mdx mouse has emerged as a more severe model of Duchenne muscular dystroph... more SummaryThe DBA/2J (D2) mdx mouse has emerged as a more severe model of Duchenne muscular dystrophy when compared to the traditional C57BL/10 (C57) mdx mouse. Here, we questioned whether sarco(endo)plasmic reticulum Ca2+-ATPase (SERCA) function would differ in muscles from young D2 and C57 mdx mice. In gastrocnemius muscles, both D2- and C57 mdx mice exhibited signs of impaired Ca2+ uptake, however, this was more severe in D2 mdx mice. Maximal SERCA activity was lowered only in D2 mdx gastrocnemius muscles and not C57 mdx muscles. Furthermore, in the left ventricle and diaphragm, Ca2+ uptake was impaired in C57 mdx muscles with lowered rates of Ca2+ uptake compared with C57 WT mice, whereas in muscles from D2 mdx mice, rates of Ca2+ uptake were unattainable due to the severe impairments in their ability to transport Ca2+. Overall, our study demonstrates that SERCA function is drastically impaired in young D2 mdx mice.

Physiological Reports, 2020

This is an open access article under the terms of the Creative Commons Attribution License, which... more This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

The FASEB Journal, 2020

Activation of white adipose tissue (WAT) thermogenesis, known as WAT browning, has emerged as an ... more Activation of white adipose tissue (WAT) thermogenesis, known as WAT browning, has emerged as an attractive approach to treat obesity and obesity‐related diseases. Traditionally BAT or browning WAT has been defined by the expression of uncoupling protein 1 (UCP1), a mitochondrial protein that uncouples respiration from ATP production. However, recent work has highlighted creatine metabolism or futile cycling as a potential thermogenic pathway. Creatine‐driven futile cycling is a catabolic process which results in ATP oxidation by mitochondrial creatine kinase, resulting in the phosphorylation of creatine and increases in ADP concentrations that drive thermogenic respiration. The purpose of the present study was two‐fold: 1) to determine the effects of creatine supplementation on markers of WAT browning, and 2) to determine if creatine supplementation exhibits sex differences. Thirty‐two Sprague‐Dawley rats (16 male, 16 female) were randomly assigned to one of four experimental group...

Cells, 2019

Glycogen synthase kinase 3 (GSK3) slows myogenic differentiation and myoblast fusion partly by in... more Glycogen synthase kinase 3 (GSK3) slows myogenic differentiation and myoblast fusion partly by inhibiting the Wnt/β-catenin signaling pathway. Lithium, a common medication for bipolar disorder, inhibits GSK3 via Mg + competition and increased Ser21 (GSK3α) or Ser9 (GSK3β) phosphorylation, leading to enhanced myoblast fusion and myogenic differentiation. However, previous studies demonstrating the effect of lithium on GSK3 have used concentrations up to 10 mM, which greatly exceeds concentrations measured in the serum of patients being treated for bipolar disorder (0.5-1.2 mM). Here, we determined whether a low-therapeutic (0.5 mM) dose of lithium could promote myoblast fusion and myogenic differentiation in C2C12 cells. C2C12 myotubes differentiated for three days in media containing 0.5 mM lithium chloride (LiCl) had significantly higher GSK3β (ser9) and GSK3α (ser21) phosphorylation compared with control myotubes differentiated in the same media without LiCl (+2-2.5 fold, p < 0.05), a result associated with an increase in total β-catenin. To further demonstrate that 0.5 mM LiCl inhibited GSK3 activity, we also developed a novel GSK3-specific activity assay. Using this enzyme-linked spectrophotometric assay, we showed that 0.5 mM LiCl-treated myotubes had significantly reduced GSK3 activity (−86%, p < 0.001). Correspondingly, 0.5 mM LiCl treated myotubes had a higher myoblast fusion index compared with control (p < 0.001) and significantly higher levels of markers of myogenesis (myogenin, +3-fold, p < 0.001) and myogenic differentiation (myosin heavy chain, +10-fold, p < 0.001). These results indicate that a low-therapeutic dose of LiCl is sufficient to promote myoblast fusion and myogenic differentiation in muscle cells, which has implications for the treatment of several myopathic conditions.