ORCID Profile
0000-0002-6011-7126
Current Organisations
University of Tasmania
,
Baker Heart and Diabetes Institute
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Publisher: American Physiological Society
Date: 05-2020
DOI: 10.1152/JAPPLPHYSIOL.00850.2019
Abstract: This is the largest study to date to examine the effects of inorganic nitrate supplementation in patients with heart failure with reduced ejection fraction (HFrEF) and the first to include measures of vascular function and mitochondrial respiration. Although daily supplementation increased plasma nitrite, our data indicate that supplementation with inorganic nitrate as a standalone treatment is ineffective at improving exercise capacity, vascular function, or mitochondrial respiration in patients with HFrEF.
Publisher: Wiley
Date: 02-12-2019
Publisher: Cold Spring Harbor Laboratory
Date: 07-07-2020
DOI: 10.1101/2020.07.06.190702
Abstract: To investigate if there is a causal relationship between changes in insulin resistance and mitochondrial respiratory function and content in rats fed a high fat diet (HFD) with or without concurrent exercise training. We hypothesised that provision of a high fat diet (HFD) would increase insulin resistance and decrease mitochondrial characteristics (content and function), and that exercise training would improve both mitochondrial characteristics and insulin resistance in rats fed a HFD. Male Wistar rats were given either a chow diet or a high fat diet (HFD) for 12 weeks. After 4 weeks of the dietary intervention, half of the rats in each group began eight weeks of interval training. In vivo glucose and insulin tolerance was assessed, as was ex vivo glucose uptake in epitrochlearis muscle. Mitochondrial respiratory function was assessed in permeabilised soleus and white gastrocnemius (WG) muscles. Mitochondrial content was determined by measurement of citrate synthase (CS) activity and protein expression of components of the electron transport system (ETS). HFD rats had impaired glucose and insulin tolerance. HFD did not change CS activity in the soleus however, it did increase CS activity in WG (Chow 5.9 ± 0.5, HFD 7.2 ± 0.7 mol h -1 kg protein -1 ). Protein expression of components of the ETS and mitochondrial respiratory function (WG Chow 65.2 ± 8.4, HFD 88.6 ± 8.7 pmol O2 s -1 mg -1 ) were also increased by HFD. Exercise training improved glucose and insulin tolerance in the HFD rats. Exercise training did not alter CS activity in either muscle. Mitochondrial respiratory function was increased with exercise training in the chow fed animals in soleus muscle, but not in WG. This exercise effect was absent in the HFD animals. Mitochondrial characteristics did not consistently correlate with insulin or glucose tolerance. HFD induced insulin resistance, but it did not negatively affect any of the measured mitochondrial characteristics. Exercise training improved insulin resistance, but without changes in mitochondrial respiration and content. The lack of an association between mitochondrial characteristics and insulin resistance was reinforced by the absence of strong correlations between these measures. Our results suggest that defects in mitochondrial respiration and content are not responsible for insulin resistance in HFD rats.
Publisher: Public Library of Science (PLoS)
Date: 10-10-2016
Publisher: Informa UK Limited
Date: 31-01-2019
DOI: 10.1080/07420528.2019.1567524
Abstract: The present paper endeavored to elucidate the topic on the effects of morning versus evening resistance training on muscle strength and hypertrophy by conducting a systematic review and a meta-analysis of studies that examined time of day-specific resistance training. This systematic review was performed in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines with searches conducted through PubMed/MEDLINE, Scopus, and SPORTDiscus databases. The Downs and Black checklist was used for the assessment of the methodological quality of the included studies. Studies that examined the effects of time of day-specific resistance training (while equating all other training variables, such as training frequency and volume, between the groups) on muscle strength and/or muscle size were included in the present review. The random effects model was used for the meta-analysis. Meta-analyses explored (1) the differences in strength expression between morning and evening hours at baseline (2) the differences in strength within the groups training in the morning and evening by using their post-intervention strength data from the morning and evening strength assessments (3) the overall differences between the effects of morning and evening resistance training (with subgroup analyses conducted for studies that assessed strength in the morning hours and for the studies that assessed strength in the evening hours). Finally, a meta-analysis was also conducted for studies that assessed muscle hypertrophy. Eleven studies of moderate and good methodological quality were included in the present review. The primary findings of the review are as follows: (1) at baseline, a significant difference in strength between morning and evening is evident, with greater strength observed in the evening hours (2) resistance training in the morning hours may increase strength assessed in the morning to similar levels as strength assessed in the evening (3) training in the evening hours, however, maintains the general difference in strength across the day, with greater strength observed in the evening hours (4) when comparing the effects between the groups training in the morning versus in the evening hours, increases in strength are similar in both groups, regardless of the time of day at which strength assessment is conducted and (5) increases in muscle size are similar irrespective of the time of day at which the training is performed.
Publisher: Wiley
Date: 06-01-2021
DOI: 10.1113/JP279411
Abstract: Mitochondria are dynamic organelles, intricately designed to meet cellular energy requirements. To accommodate alterations in energy demand, mitochondria have a high degree of plasticity, changing in response to transient activation of numerous stress‐related pathways. This adaptive response is particularly relevant in highly metabolic tissues such as skeletal muscle, where mitochondria support numerous biological processes related to metabolism, growth and regeneration. Aerobic exercise is a potent stimulus for skeletal muscle remodelling, leading to alterations in substrate utilisation, fibre‐type composition and performance. Underlying these physiological responses is a change in mitochondrial quality control (MQC), a term encompassing the co‐ordination of mitochondrial synthesis (biogenesis), remodelling (dynamics) and degradation (mitophagy) pathways. Understanding of MQC in skeletal muscle and the regulatory role of aerobic exercise of this process are rapidly advancing, as are the molecular techniques allowing the study of MQC in vivo . Given the emerging link between MQC and the onset of numerous non‐communicable diseases, understanding the molecular regulation of MQC, and the role of aerobic exercise in this process, will have substantial future impact on therapeutic approaches to manipulate MQC and maintain mitochondrial function across health span. image
Publisher: Cold Spring Harbor Laboratory
Date: 25-03-2021
DOI: 10.1101/2021.03.25.436899
Abstract: The assessment of mitochondrial respiration and mitochondrial content are two common measurements in the fields of skeletal muscle research and exercise science. However, to verify the validity of the observed changes in both mitochondrial respiration and mitochondrial content following an intervention such as exercise training, it is important to determine the reliability and reproducibility of the experimental design and/or techniques employed. We examined the repeatability of widely used methodologies for assessing mitochondrial respiration and mitochondrial content, respectively the measurement of maximal mitochondrial oxidative phosphorylation in permeabilized muscle fibres using high-resolution respirometry, and the measurement of citrate synthase activity as a biomarker for mitochondrial content in a microplate with spectrophotometer. For mitochondrial respiration, the coefficient of variation for repeated measurements using muscle s led from same biopsy decreased from 12.7% to 11% when measured in triplicate with outliers excluded, rather than in duplicate. The coefficient of variation was 9.7% for repeated muscle biopsies s led across two separated days. For measurements of citrate synthase activity, the coefficient of variation was 3.5% of three technical repeats on the same plate, 10.2% for duplicate analyses using the same muscle lysate when conducted in the same day, and 30.5% when conducted four weeks apart. We have provided evidence for important technical considerations when measuring mitochondrial respiration with human skeletal muscle: 1) the relatively large technical variability can be reduced by increasing technical repeats and excluding outliers 2) the biological variability and absolute mitochondrial respiration value of the participants should be considered when estimating the required s le size 3) a new threshold of 15% for the increase in respiration rate after the addition of cytochrome c test for testing mitochondrial outer membrane integrity. When analysing citrate synthase activity, our evidence suggests it is important to consider the following: 1) all s les from the same study should be homogenized and measured at the same time using the same batch of freshly made chemical reagents 2) biological variability should be considered when detecting small change in mitochondrial content 3) the relative change should be used to compare the outcomes from different studies.
Publisher: Wiley
Date: 04-08-2020
DOI: 10.1113/JP280366
Publisher: Elsevier BV
Date: 11-2202
Publisher: Cold Spring Harbor Laboratory
Date: 21-06-2020
DOI: 10.1101/2020.06.21.163733
Abstract: Sleep loss has emerged as a risk factor for the development of impaired glucose tolerance. The mechanisms underpinning this observation are unknown however, both mitochondrial dysfunction and circadian misalignment have been proposed. Given that exercise improves glucose tolerance, mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects induced by inadequate sleep. We report that sleeping 4 hours per night, for five nights, reduced glucose tolerance, with novel observations of associated reductions in mitochondrial function, sarcoplasmic protein synthesis, and measures of circadian rhythmicity however, incorporating three sessions of high-intensity interval exercise (HIIE) during this period mitigates these effects. These data demonstrate, for the first time, a sleep loss-induced concomitant reduction in a range of physiological processes linked to metabolic function. These same effects are not observed when exercise is performed during a period of inadequate sleep, supporting the use of HIIE as an intervention to mitigate the detrimental physiological effects of sleep loss.
Publisher: American Physiological Society
Date: 2019
DOI: 10.1152/PHYSIOL.00038.2018
Abstract: It is well established that different types of exercise can provide a powerful stimulus for mitochondrial biogenesis. However, there are conflicting findings in the literature, and a consensus has not been reached regarding the efficacy of high-intensity exercise to promote mitochondrial biogenesis in humans. The purpose of this review is to examine current controversies in the field and to highlight some important methodological issues that need to be addressed to resolve existing conflicts.
Publisher: Elsevier BV
Date: 2020
Publisher: Wiley
Date: 11-07-2023
DOI: 10.1111/JSR.13987
Abstract: Mood state and alertness are negatively affected by sleep loss, and can be positively influenced by exercise. However, the potential mitigating effects of exercise on sleep‐loss‐induced changes in mood state and alertness have not been studied comprehensively. Twenty‐four healthy young males were matched into one of three, 5‐night sleep interventions: normal sleep (NS total sleep time (TST) per night = 449 ± 22 min), sleep restriction (SR TST = 230 ± 5 min), or sleep restriction and exercise (SR + EX TST = 235 ± 5 min, plus three sessions of high‐intensity interval exercise (HIIE)). Mood state was assessed using the profile of mood states (POMS) and a daily well‐being questionnaire. Alertness was assessed using psychomotor vigilance testing (PVT). Following the intervention, POMS total mood disturbance scores significantly increased for both the SR and SR + EX groups, and were greater than the NS group (SR vs NS 31.0 ± 10.7 A.U., [4.4–57.7 A.U.], p = 0.020 SR + EX vs NS 38.6 ± 14.9 A.U., [11.1–66.1 A.U.], p = 0.004). The PVT reaction times increased in the SR ( p = 0.049) and SR + EX groups ( p = 0.033) and the daily well‐being questionnaire revealed increased levels of fatigue in both groups (SR p = 0.041, SR + EX p = 0.026) during the intervention. Despite previously demonstrated physiological benefits of performing three sessions of HIIE during five nights of sleep restriction, the detriments to mood, wellness, and alertness were not mitigated by exercise in this study. Whether alternatively timed exercise sessions or other exercise protocols could promote more positive outcomes on these factors during sleep restriction requires further research.
Publisher: Wiley
Date: 25-10-2018
DOI: 10.1113/JP276841
Publisher: Wiley
Date: 03-2021
DOI: 10.14814/PHY2.14797
Publisher: Cold Spring Harbor Laboratory
Date: 06-08-2020
DOI: 10.1101/2020.08.05.239038
Abstract: Exercise elicits a range of adaptive responses in skeletal muscle that include changes in mRNA expression. To better understand the health benefits of exercise training, it is essential to investigate the underlying molecular mechanisms of skeletal muscle adaptations to exercise. However, most studies have assessed the molecular events at a few convenient time points within a short time frame post exercise, and the variations of gene expression kinetics have not been addressed systematically. Muscle biopsies were collected from nine participants at baseline and six time points (0, 3, 9, 24, 48, and 72 h) following a session of high-intensity interval exercise. We assessed the mRNA content of 23 gene isoforms from the muscle s les. The temporal patterns of target gene expression were highly variable and the mRNA contents detected were largely dependent on the muscle s le timing. The maximal levels of mRNA content of all tested target genes were observed between 3 to 48 h post exercise. Our findings highlight a critical gap in knowledge regarding the molecular response to exercise, where the use of a few time points within a short period after exercise has led to an incomplete understanding of the molecular responses to exercise. The timing of muscle s ling for in idual studies needs to be carefully chosen based on existing literature and preliminary analysis of the molecular targets of interest. We propose that a comprehensive time-course analysis on the exercise-induced transcriptional response in humans will significantly benefit the field of exercise molecular biology.
Publisher: Wiley
Date: 11-03-2020
DOI: 10.1113/JP278828
Abstract: Sleep restriction has previously been associated with the loss of muscle mass in both human and animal models. The rate of myofibrillar protein synthesis (MyoPS) is a key variable in regulating skeletal muscle mass and can be increased by performing high‐intensity interval exercise (HIIE), although the effect of sleep restriction on MyoPS is unknown. In the present study, we demonstrate that participants undergoing a sleep restriction protocol (five nights, with 4 h in bed each night) had lower rates of skeletal muscle MyoPS however, rates of MyoPS were maintained at control levels by performing HIIE during this period. Our data suggest that the lower rates of MyoPS in the sleep restriction group may contribute to the detrimental effects of sleep loss on muscle mass and that HIIE may be used as an intervention to counteract these effects. The present study aimed to investigate the effect of sleep restriction, with or without high‐intensity interval exercise (HIIE), on the potential mechanisms underpinning previously‐reported sleep‐loss‐induced reductions to muscle mass. Twenty‐four healthy, young men underwent a protocol consisting of two nights of controlled baseline sleep and a five‐night intervention period. Participants were allocated into one of three parallel groups, matched for age, , body mass index and habitual sleep duration a normal sleep (NS) group [8 h time in bed (TIB) each night], a sleep restriction (SR) group (4 h TIB each night), and a sleep restriction and exercise group (SR+EX, 4 h TIB each night, with three sessions of HIIE). Deuterium oxide was ingested prior to commencing the study and muscle biopsies obtained pre‐ and post‐intervention were used to assess myofibrillar protein synthesis (MyoPS) and molecular markers of protein synthesis and degradation signalling pathways. MyoPS was lower in the SR group [fractional synthetic rate (% day –1 ), mean ± SD, 1.24 ± 0.21] compared to both the NS (1.53 ± 0.09) and SR+EX groups (1.61 ± 0.14) ( P 0.05). However, there were no changes in the purported regulators of protein synthesis (i.e. p‐AKT ser473 and p‐mTOR ser2448 ) and degradation (i.e. Foxo1/3 mRNA and LC3 protein) in any group. These data suggest that MyoPS is acutely reduced by sleep restriction, although MyoPS can be maintained by performing HIIE. These findings may explain the sleep‐loss‐induced reductions in muscle mass previously reported and also highlight the potential therapeutic benefit of HIIE to maintain myofibrillar remodelling in this context.
Publisher: Cold Spring Harbor Laboratory
Date: 12-02-2019
DOI: 10.1101/547489
Abstract: Endurance exercise begun with reduced muscle glycogen stores seems to potentiate skeletal muscle protein abundance and gene expression. However, it is unknown whether this greater signalling responses is due to low muscle glycogen per se or to performing two exercise sessions in close proximity - as a first exercise session is necessary to reduce the muscle glycogen stores. In the present study, we manipulated the recovery duration between a first muscle glycogen-depleting exercise and a second exercise session, such that the second exercise session started with reduced muscle glycogen in both approaches but was performed either two or 15 h after the first exercise session (so-called “twice-a-day” and “once-daily” approaches, respectively). We found that exercise twice-a-day increased the nuclear abundance of transcription factor EB (TFEB) and nuclear factor of activated T cells (NFAT) and potentiated the transcription of peroxisome proliferator-activated receptor-coactivator 1 alpha (PGC-1α), peroxisome proliferator-activated receptor alpha (PPARα) and peroxisome proliferator-activated receptor beta/delta (PPARβ/δ) genes, in comparison with the once-daily exercise. These results suggest that the elevated molecular signalling reported with previous “train-low” approaches can be attributed to performing two exercise sessions in close proximity rather than the reduced muscle glycogen content per se. The twice-a-day approach might be an effective strategy to induce adaptations related to mitochondrial biogenesis and fat oxidation.
Publisher: Elsevier BV
Date: 02-2018
DOI: 10.1016/J.SMRV.2017.01.001
Abstract: Sleep loss has emerged as a risk factor comparable to that of physical inactivity for the development of insulin resistance, impaired glucose tolerance and type 2 diabetes mellitus. This is a concern as it was estimated in 2012 that approximately 70 million adults in the United States are sleeping less than 6 h each night, and the average nightly sleep duration of a representative s le of the U.S. adult population is reported to be significantly less than in previous decades. The underlying mechanisms responsible for chronic sleep loss induced insulin resistance include modifications in the regulation of hormone secretion, peripheral clock gene regulation, and the cellular signaling processes associated with regulating mitochondrial respiratory function. Emerging evidence shows these mechanisms share similar biochemical signaling pathways to those underpinning exercise-induced adaptations, which together suggest exercise might be a viable, suitable, and potent treatment alternative to alleviate sleep loss induced insulin resistance and glucose intolerance. In this theoretical review, we provide a summary of the impact of reduced sleep duration and quality on mitochondrial function and insulin resistance, before detailing the possible underlying mechanisms. Finally, we propose how and why regular exercise may be a therapeutic intervention to mitigate sleep loss induced mitochondrial dysfunction and insulin resistance.
No related grants have been discovered for Nicholas Saner.