Cited by 68Sleep and Work-Related FatigueCircadian rhythm and melatoninSleep and related disorders

Exercise mitigates sleep-loss-induced changes in glucose tolerance, mitochondrial function, sarcoplasmic protein synthesis, and diurnal rhythms

Open access
Saner, Nicholas J., Lee, Matthew J-C., Kuang, Jujiao, Pitchford, Nathan W., Roach, Gregory D., Garnham, Andrew, Genders, Amanda J., Stokes, Tanner +6 more·2021·Molecular Metabolism

Published version of a preprint

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. Because exercise improves glucose tolerance and mitochondrial function, and alters circadian rhythms, we investigated whether exercise may counteract the effects induced by inadequate sleep. To minimize between-group differences of baseline characteristics, 24 healthy young males were allocated into one of the three experimental groups: a Normal Sleep (NS) group (8 h time in bed (TIB) per night, for five nights), a Sleep Restriction (SR) group (4 h TIB per night, for five nights), and a Sleep Restriction and Exercise group (SR+EX) (4 h TIB per night, for five nights and three high-intensity interval exercise (HIIE) sessions). Glucose tolerance, mitochondrial respiratory function, sarcoplasmic protein synthesis (SarcPS), and diurnal measures of peripheral skin temperature were assessed pre- and post-intervention. We report that the SR group had reduced glucose tolerance post-intervention (mean change ± SD, P value, SR glucose AUC: 149 ± 115 A.U., P = 0.002), which was also associated with reductions in mitochondrial respiratory function (SR: -15.9 ± 12.4 pmol O2.s−1.mg−1, P = 0.001), a lower rate of SarcPS (FSR%/day SR: 1.11 ± 0.25%, P < 0.001), and reduced amplitude of diurnal rhythms. These effects were not observed when incorporating three sessions of HIIE during this period (SR+EX: glucose AUC 67 ± 57, P = 0.239, mitochondrial respiratory function: 0.6 ± 11.8 pmol O2.s−1.mg−1, P = 0.997, and SarcPS (FSR%/day): 1.77 ± 0.22%, P = 0.971). A five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance. We provide novel data demonstrating that these same detrimental effects are not observed when HIIE is performed during the period of sleep restriction. These data therefore provide evidence in support of the use of HIIE as an intervention to mitigate the detrimental physiological effects of sleep loss.

AI snapshot

Written from the paper’s full text.

TL;DR

In healthy young men, five nights of sleep restriction (4 h time in bed/night) reduced glucose tolerance, skeletal muscle mitochondrial respiratory function, sarcoplasmic protein synthesis, and diurnal skin-temperature rhythm amplitude. Performing three sessions of high-intensity interval exercise during the same sleep-restriction period prevented these changes.

Key findings

  • Sleep restriction increased glucose AUC (mean change ± SD: 149 ± 115 A.U., P = 0.002; pre 678 ± 92 vs post 827 ± 56 A.U., P = 0.002), whereas the sleep restriction plus exercise group did not show a significant increase (67 ± 57 A.U., P = 0.239).
  • Maximal coupled mitochondrial respiration fell in the sleep-restriction group (−15.9 ± 12.4 pmol O2.s−1.mg−1, P = 0.001; 18% decrease) but not in the sleep restriction plus exercise group (0.6 ± 11.8 pmol O2.s−1.mg−1, P = 0.997).
  • Sarcoplasmic protein synthesis fractional synthetic rate was lower in the sleep-restriction group (1.11 ± 0.25%/day, P < 0.001) than in normal sleep and sleep restriction plus exercise groups; the sleep restriction plus exercise group was 1.77 ± 0.22%/day (P = 0.971 vs normal sleep).
  • Wrist skin-temperature diurnal amplitude decreased significantly within both sleep-restriction (P = 0.008) and sleep restriction plus exercise (P = 0.008) groups, but the pre-post difference between sleep restriction and normal sleep approached significance (P = 0.055); no changes were seen in mitochondrial content markers (citrate synthase activity or mitochondrial complex subunit proteins) or in measured clock gene/protein markers.

Methods

  • Twenty-four healthy, recreationally active men aged 18–40 were allocated by minimization into three parallel groups (n = 8 each): Normal Sleep (8 h TIB/night for five nights), Sleep Restriction (4 h TIB/night for five nights), and Sleep Restriction and Exercise (4 h TIB/night plus three HIIE sessions on days 4, 5, and 6).
  • The HIIE protocol was 10 × 60-second cycling intervals at 90% peak power, separated by 75 seconds of active recovery at 60 W; mean interval power was 318 ± 53 W and mean heart rate was 156 ± 13 bpm.
  • Pre- and post-intervention assessments included oral glucose tolerance tests, skeletal muscle biopsies with high-resolution respirometry, deuterium oxide-based sarcoplasmic protein synthesis, wrist skin-temperature monitoring over 48-h periods, and qPCR/western blotting; analyses used mixed ANOVA with Bonferroni post-hoc tests, with circadian temperature parameters analyzed by sinusoid fitting and linear mixed models.

Limitations

  • The authors state that a parallel group design was chosen because of the challenging and invasive protocol, that muscle samples were collected after the OGTT and may have altered molecular signaling, and that a normal sleep plus exercise group was not included, limiting the ability to isolate the contribution of HIIE.
  • Evident from the text: the sample was small (n = 8 per group), included only healthy young men, and used a short five-night sleep-restriction period; PSG was performed in only a subset (n = 12; 4 per group), and some molecular outcomes may have been underpowered or sampled at times that missed transient changes.

Model-written summary. Check it against the paper before relying on it.

Integrity signals

Registry

Crossref · 10.1016/j.molmet.2020.101110

Cites

70 of 70 references verified0 citation errors · 0 not checkable

Statistics

Nothing to recompute.

Claims the paper makes

0 of 99 cited sources checked · 0 supported · 0 flagged

  • Findingown data

    Sarcoplasmic fraction citrate synthase activity was significantly higher than whole-muscle fractions.

    “and whole-muscle fractions (0.74 ± 0.44, CI [-1.40, −0.07], P = 0.027)”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no difference in SarcPS between the NS and SR+EX groups.

    “there was no difference in SarcPS between the NS and SR+EX groups (0.04 ± 0.10%, CI [-0.33, 0.24], P > 0.999)”
    Quote in the paperSubstantial claim
  • Findingown data

    In the sleep restriction plus exercise group, three sessions of high-intensity interval exercise during sleep restriction did not lower sarcoplasmic protein synthesis (FSR%/day: 1.77 ± 0.22%, P = 0.971).

    “and SarcPS (FSR%/day): 1.77 ± 0.22%, P = 0.971).”
    • Also stated in: § Conclusions · boosted
      “We provide novel data demonstrating that these same detrimental effects are not observed when HIIE is performed during the period of sleep restriction.”
    Quote in the paperSubstantial claim
  • Findingown data

    There was no significant change in insulin AUC within any group from pre- to post-intervention.

    “There was no significant change (interaction P = 0.085, day P = 0.225, group P = 0.130) in insulin AUC within any group pre- to post-intervention”
    Quote in the paperNot a substantial claim
  • Findingown data

    Mean insulin AUC increased by 29% following the SR intervention.

    “despite a 29% increase in mean insulin AUC following the SR intervention”
    • Also stated in: § Discussion · plain
      “Furthermore, the plasma insulin response during the OGTT for the SR group increased by 29% from pre- to post-intervention (although not statistically significant).”
    Quote in the paperNot a substantial claim
  • The quote only partly states this claim. 5
  • May combine two claims. 27
  • Classified as probably not a substantial claim. 40
  • The quote only partly states this claim.

    Findingown data

    In healthy young males, five nights of sleep restriction reduced mitochondrial respiratory function (SR: -15.9 ± 12.4 pmol O2.s−1.mg−1, P = 0.001).

    “which was also associated with reductions in mitochondrial respiratory function (SR: -15.9 ± 12.4 pmol O2.s−1.mg−1, P = 0.001)”
    • Also stated in: § Conclusions · plain
      “A five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim.

    Findingown data

    In healthy young males, five nights of sleep restriction lowered the rate of sarcoplasmic protein synthesis (FSR%/day SR: 1.11 ± 0.25%, P < 0.001).

    “a lower rate of SarcPS (FSR%/day SR: 1.11 ± 0.25%, P < 0.001)”
    • Also stated in: § Conclusions · plain
      “A five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance.”
    Quote in the paperSubstantial claim
  • The quote only partly states this claim.

    Findingown data

    In healthy young males, five nights of sleep restriction reduced the amplitude of diurnal rhythms.

    “and reduced amplitude of diurnal rhythms.”
    • Also stated in: § Conclusions · plain
      “A five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    There were no significant differences within groups from pre- to post-intervention, or between groups, for PGC-1α, DRP1, MFN2, p53, BMAL1, or GLUT4 protein content.

    “However, there were no significant differences within groups from pre- to post-intervention, or between groups (P > 0.05) for PGC-1α, DRP1, MFN2, p53, BMAL1, or GLUT4 protein content (Figure 6).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    There were no differences in basal wrist skin temperature either pre- or post-intervention or between groups.

    “As shown in Figure 2A, there were no differences observed in basal skin temperature either pre- or post-intervention or between groups.”
    Quote in the paperNot a substantial claim
  • The quote only partly states this claim.

    Findingown data

    In healthy young males, five nights of sleep restriction (4 h time in bed per night) reduced glucose tolerance post-intervention (SR glucose AUC mean change 149 ± 115 A.U., P = 0.002).

    “We report that the SR group had reduced glucose tolerance post-intervention (mean change ± SD, P value, SR glucose AUC: 149 ± 115 A.U., P = 0.002)”
    • Also stated in: § Conclusions · plain
      “A five-night period of sleep restriction leads to reductions in mitochondrial respiratory function, SarcPS, and amplitude of skin temperature diurnal rhythms, with a concurrent reduction in glucose tolerance.”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    The coefficient of fit to the circadian waveform (R2) did not change in the NS group, but significantly decreased from pre- to post-intervention in the SR and SR+EX groups.

    “Similar to diurnal amplitude, we did not see a change in R2 for the NS group, but did observe significantly decreased R2 when comparing pre- and post-intervention values for SR (P = 0.004) and SR+EX (P = 0.009).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    There was a 33% change in Glut4 mRNA (not statistically significant) in the SR group, with no change in GLUT4 protein.

    “At the molecular level, we reported a 33% change in Glut4 mRNA (that was not statistically significant) in the SR group, with no change in GLUT4 protein.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    Despite a non-significant 35 ± 28% change in Mfn2 mRNA in the SR group, there were no changes in the molecular regulators of mitochondrial dynamics.

    “However, despite a non-significant 35 ± 28% change in Mfn2 mRNA in the SR group, we observed no changes in the molecular regulators of mitochondrial dynamics.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Findingown data

    There were no changes to the protein content of mitochondrial complex subunits or CS activity.

    “There were no changes to the protein content of mitochondrial complex subunits or CS activity, both of which are valid markers of mitochondrial content [16].”
    Quote in the paperSubstantial claim
  • May combine two claims.

    Findingown data

    At the skeletal muscle level, there were no changes in circadian clock genes, despite a 29 ± 33% reduction in Bmal1 mRNA in the SR group.

    “However, at the skeletal muscle level, we did not see any changes in circadian clock genes (despite a 29 ± 33%, reduction in Bmal1 mRNA in the SR group).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Inadequate sleep is a consequence of many occupations.

    “and inadequate sleep is a consequence of many occupations [12,13]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [12] Luxton, 2011, Prevalence and impact of short sleep duration in redeployed OIF soldiers, Sleep source

      Not checked in the free run.

    • cites [13] Akerstedt, 2009, Sleep loss and fatigue in shift work and shift work disorder, Sleep Medicine Clinics source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    A large proportion of the population do not meet current sleep recommendations of 7-9 h per night.

    “As a large proportion of the population do not meet the current sleep recommendations (7–9 h per night) [10,11]”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [10] Hillman, 2018, The economic cost of inadequate sleep, Sleep source

      Not checked in the free run.

    • cites [11] Ford, 2015, Trends in self-reported sleep duration among US adults from 1985 to 2012, Sleep source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Genetic mouse models with disrupted molecular clock (Clock mutant mice and Bmal1 KO mouse) display reduced glucose tolerance, mitochondrial respiratory function, and skeletal muscle contractile function.

    “The functional significance of disrupting the molecular clock has been shown in genetic mouse models (i.e., Clock mutant mice and the Bmal1 KO mouse), which display reduced glucose tolerance, mitochondrial respiratory function, and skeletal muscle contractile function [20,21].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [20] Pastore, 1985, Endurance training ameliorates the metabolic and performance characteristics of circadian Clock mutant mice, Journal of Applied Physiology source

      Not checked in the free run.

    • cites [21] Andrews, 2010, CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function, Proceedings of the National Academy of Sciences of the U S A source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High-intensity interval exercise is a time-efficient format of endurance exercise and a potent stimulus for induction of mitochondrial biogenesis.

    “High-intensity interval exercise (HIIE) is a time-efficient format of endurance exercise and also a potent stimulus for the induction of mitochondrial biogenesis [23]”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [23] Bishop, 2019, High-intensity exercise and mitochondrial biogenesis: current controversies and future research directions, Physiology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    High-intensity interval exercise increases sarcoplasmic and mitochondrial protein synthesis and mitochondrial content and respiratory function, occurring concomitantly with improvements in glucose tolerance.

    “with increase in sarcoplasmic and mitochondrial protein synthesis and mitochondrial content and respiratory function, occurring concomitantly with improvements in glucose tolerance [[24], [25], [26], [27]].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [[24], [25], [26], [27]]

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductcitation

    Sleep was assessed using wrist-watch activity devices (Actiwatch 2).

    “Sleep was assessed for one week prior to and then throughout the study using wrist-watch activity devices (Actiwatch 2, Philips Respironics, Murrysville, PA, USA) [34].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [34] Stone, 2016, Actigraphy

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    High-intensity interval exercise may mitigate the detrimental effects of sleep loss on glucose metabolism by increasing mitochondrial content and function and preventing changes in circadian rhythmicity.

    “Consequently, HIIE may mitigate the detrimental effects of sleep loss on glucose metabolism by increasing mitochondrial content and function and preventing changes in circadian rhythmicity [17].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [17] Saner, 2018, Is exercise a viable therapeutic intervention to mitigate mitochondrial dysfunction and insulin resistance induced by sleep loss?, Sleep Medicine Reviews source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Clock genes and clock proteins are known to regulate circadian rhythms at a molecular level.

    “which are known to regulate circadian rhythms at a molecular level [19].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [19] Bunger, 2000, Mop3 is an essential component of the master circadian pacemaker in mammals, Cell source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductnone given

    Participants were allocated via minimization into three experimental groups in a counterbalanced order to minimize between-group baseline differences in age, BMI, habitual sleep duration, V̇O2peak, and mitochondrial respiratory function.

    “Following baseline testing, the participants were allocated via minimization into one of the three experimental groups, in a counterbalanced order, so as to minimize differences in between-group baseline measures for age, BMI, habitual sleep duration, V˙´O2peak, and mitochondrial respiratory function (Table 1).”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Changes in amplitude of a diurnal rhythm provide an indication of the robustness of the rhythm.

    “changes in amplitude have previously been proposed to provide an indication of the robustness of the rhythm [39,43].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [39] Tranel, 2015, Physical activity, and not fat mass is a primary predictor of circadian parameters in young men, Chronobiology International source

      Not checked in the free run.

    • cites [43] Wilkinson, 2014, A validation of the application of D(2)O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans, American Journal of Physiology. Endocrinology and Metabolism source

      Not checked in the free run.

  • May combine two claims.

    Interpretationreasoning

    Because wrist skin temperature measures were obtained under everyday life conditions with regular meals and activity, they reflect diurnal rhythms, as opposed to circadian rhythms.

    “As these measures were obtained under everyday life conditions, with regular meals and activity, they reflect diurnal rhythms, as opposed to circadian rhythms.”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Study design and conductcitation

    Wrist skin temperature measurement is reliable and valid for evaluating temperature circadian rhythmicity.

    “This method has been shown to be reliable and valid for evaluating temperature circadian rhythmicity, with peripheral wrist skin temperature reported to have an inverse relationship to core body temperature [38,39].”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [38] Sarabia, 2008, Circadian rhythm of wrist temperature in normal-living subjects A candidate of new index of the circadian system, Physiology & Behavior source

      Not checked in the free run.

    • cites [39] Tranel, 2015, Physical activity, and not fat mass is a primary predictor of circadian parameters in young men, Chronobiology International source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductown data

    Polysomnography was used to confirm actigraphy total sleep time data and to assess sleep architecture on night 6 of the study.

    “Polysomnography (PSG), considered the gold standard assessment of sleep [47], was used to confirm actigraphy TST data and to also assess sleep architecture on night 6 of the study (n = 4 per group) (Supplementary Figure 1).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Carskadon, 2016, Normal human sleep

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Total body water 2H enrichment was used as a surrogate for plasma alanine 2H labelling.

    “Total body water 2H enrichment was used as a surrogate for plasma alanine 2H labelling, as previously described [43].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [43] Wilkinson, 2014, A validation of the application of D(2)O stable isotope tracer techniques for monitoring day-to-day changes in muscle protein subfraction synthesis in humans, American Journal of Physiology. Endocrinology and Metabolism source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). The quote only partly states this claim.

    Study design and conductcitation

    Sleep architecture, duration, and quality were determined via polysomnography and scored according to standard criteria.

    “Sleep architecture, duration, and quality were also determined via polysomnography (PSG) (Compumedics, AUS) on night 6 for a subset of participants from each condition (n = 12; 4 per group). Electrode placement for PSG monitoring was determined using the 10–20 electrode placement system and scored in accordance to standard criteria [35].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [35] Iber, 2007

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Mitochondrial respiration was measured in triplicate with a coefficient of variation of 12%.

    “Mitochondrial respiration was measured in triplicate (coefficient of variation [CV] = 12%) (from 2 to 4 mg wet weight of muscle fibers) in MiR05 at 37 °C using the high-resolution Oxygraph-2k (Oroboros, Innsbruck, Austria).”
    Quote in the paperNot a substantial claim
  • May combine two claims.

    Interpretationown data

    Sleep loss is associated with decreased mitochondrial respiratory function, and this decrease was not observed in the SR+EX group.

    “These results show for the first time that sleep loss is associated with decreased mitochondrial respiratory function, which was not observed in the SR+EX group.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed changes in glucose tolerance, mitochondrial function, and diurnal rhythms are attributable to the sleep restriction intervention rather than to other uncontrolled factors.
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductnone given

    Outer mitochondrial membrane integrity was tested by cytochrome C addition, with an oxygen flux increase of less than 15% considered acceptable.

    “Cytochrome C (10 mM) was then added to test for outer mitochondrial membrane integrity (an oxygen flux increase of <15% from (ETF+CI+II)P was considered acceptable).”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductcitation

    Habitual daily step counts were monitored using validated step-counting applications and replicated throughout the study.

    “Habitual daily step counts were monitored using validated step-counting applications on the participants’ personal mobile phone devices (i-Health app, Apple Inc., Cupertino, CA, USA; and Samsung Health, Samsung Electronics Co., Ltd., Suwon, South Korea) and these step counts were replicated throughout the study (Supplementary Table 1) (data modified from [36]).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [36] Saner, 2020, The effect of sleep restriction, with or without high-intensity interval exercise, on myofibrillar protein synthesis in healthy young men, Journal of Physiology source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Mitochondrial protein synthesis (MitoPS) is the best measure of mitochondrial biogenesis.

    “It has been argued that the best measure of mitochondrial biogenesis is mitochondrial protein synthesis (MitoPS) [48].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Miller, 2012, A perspective on the determination of mitochondrial biogenesis, American Journal of Physiology. Endocrinology and Metabolism source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Peripheral wrist skin temperature has an inverse relationship to core body temperature.

    “This method has been shown to be reliable and valid for evaluating temperature circadian rhythmicity, with peripheral wrist skin temperature reported to have an inverse relationship to core body temperature [38,39].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [38] Sarabia, 2008, Circadian rhythm of wrist temperature in normal-living subjects A candidate of new index of the circadian system, Physiology & Behavior source

      Not checked in the free run.

    • cites [39] Tranel, 2015, Physical activity, and not fat mass is a primary predictor of circadian parameters in young men, Chronobiology International source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    One explanation for the observations may involve processes regulating mitochondrial dynamics/remodeling (fission and fusion), which can alter efficiency and oxidative capacity without necessarily altering mitochondrial content.

    “One explanation for our observations may involve the processes regulating mitochondrial dynamics/remodeling (i.e., fission and fusion), which can alter the efficiency and oxidative capacity of the mitochondria, without necessarily altering mitochondrial content [23].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [23] Bishop, 2019, High-intensity exercise and mitochondrial biogenesis: current controversies and future research directions, Physiology source

      Not checked in the free run.

  • May combine two claims.

    Study design and conductown data

    The study did not have a Normal Sleep and HIIE group, so it cannot ascertain whether HIIE enhanced mitochondrial function.

    “however, we do not have a Normal Sleep and HIIE group that would allow us to ascertain whether HIIE enhanced mitochondrial function.”
    Quote in the paperSubstantial claim
  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    A previous study reported that a single night of 4 h time in bed decreased insulin sensitivity with a concomitant increase in plasma acylcarnitines, suggested to indicate reduced fatty acid oxidation and impaired mitochondrial function.

    “Previously, a study in humans investigating a single night of 4 h TIB reported a decrease in insulin sensitivity with a concomitant increase in plasma acylcarnitines [9], which was suggested to be indicative of both reduced fatty acid oxidation and impaired mitochondrial function.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [9] van den Berg, 2016, A single night of sleep curtailment increases plasma acylcarnitines: novel insights in the relationship between sleep and insulin resistance, Archives of Biochemistry and Biophysics source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Polysomnography is considered the gold standard assessment of sleep.

    “Polysomnography (PSG), considered the gold standard assessment of sleep [47]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [47] Carskadon, 2016, Normal human sleep

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Previous studies have shown acute positive and protective effects of exercise on sleep-loss-induced changes in glucose tolerance, but these studies assessed glucose tolerance either immediately after or within 24 h of exercise.

    “While others have shown acute positive [49] and protective [50] effects of exercise on sleep-loss-induced changes in glucose tolerance, these studies assessed glucose tolerance either immediately after or within 24 h of exercise.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [49] Sweeney, 2019, Impaired insulin profiles following a single night of sleep restriction: the impact of acute sprint interval exercise, International Journal of Sport Nutrition and Exercise Metabolism

      Not checked in the free run.

    • cites [50] de Souza, 2017, High-intensity interval training attenuates insulin resistance induced by sleep deprivation in healthy males, Frontiers in Physiology source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    HIIE has consistently been reported to increase both SarcPS and MitoPS.

    “Moreover, HIIE has consistently been reported to increase both SarcPS and MitoPS [24,57], and this likely accounts for the higher rate of SarcPS in the SR+EX group compared to the SR group.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [24] Bell, 2015, Day-to-Day changes in muscle protein synthesis in recovery from resistance, aerobic, and high-intensity interval exercise in older men, Journals of Gerontology - Series A Biological Sciences and Medical Sciences source

      Not checked in the free run.

    • cites [57] Scalzo, 2014, Greater muscle protein synthesis and mitochondrial biogenesis in males compared with females during sprint interval training, The FASEB Journal source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationcitation

    The absence of an increase in Glut4 mRNA in the SR+EX group may be explained by the timing of the muscle sample, collected 48 h post the final exercise session, by which time Glut4 mRNA expression may have returned to baseline levels.

    “This may be explained by the timing of our muscle sample, which was collected 48 h post the final exercise session, by which time Glut4 mRNA expression may have returned to baseline levels [22,51].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [22] Richter, 2013, Exercise, GLUT4, and skeletal muscle glucose uptake, Physiological Reviews source

      Not checked in the free run.

    • cites [51] Kuang, 2020, Interpretation of exercise-induced changes in human skeletal muscle mRNA expression depends on the timing of the post-exercise biopsies, bioRxiv

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Premisecitation

    A dissociation between changes in mitochondrial content and respiratory function has previously been reported, and these properties may be differentially regulated.

    “This dissociation between changes in mitochondrial content and respiratory function has previously been reported, and it has been suggested that these properties may be differentially regulated [26,56].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [26] Granata, 2016, Training intensity modulates changes in PGC-1alpha and p53 protein content and mitochondrial respiration, but not markers of mitochondrial content in human skeletal muscle, The FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology source

      Not checked in the free run.

    • cites [56] Groennebaek, 2018, Skeletal muscle mitochondrial protein synthesis and respiration increase with low-load blood flow restricted as well as high-load resistance training, Frontiers in Physiology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Previous human studies have demonstrated diminished temperature amplitude in other populations with disrupted sleep including shift work, metabolic syndrome, and sleep-disordered breathing.

    “This is consistent with previous human studies demonstrating diminished temperature amplitude in other populations with disrupted sleep including shift work, metabolic syndrome, and sleep-disordered breathing [[62], [63], [64]].”
    Quote in the paperNot a substantial claim0 of 3 sources checked
    • cites [62] Harfmann, 2017, Temperature as a circadian marker in older human subjects: relationship to metabolic syndrome and diabetes, Journal of the Endocrine Society source

      Not checked in the free run.

    • cites [63] Martinez-Nicolas, 2017, Circadian impairment of distal skin temperature rhythm in patients with sleep-disordered breathing: the effect of CPAP, Sleep source

      Not checked in the free run.

    • cites [64] Jang, 2017, Circadian rhythm of wrist temperature among shift workers in South Korea: a prospective observational study, International Journal of Environmental Research and Public Health source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductcitation

    Target gene expression was normalized to the geometric mean of expression of the three most stably expressed reference genes using the 2−ΔΔCt method.

    “The expression of each target gene was normalized to the geometric mean of expression of the three most stably expressed reference genes (as previously described) [46] using the 2−ΔΔCt method”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [46] Kuang, 2018, An overview of technical considerations when using quantitative real-time PCR analysis of gene expression in human exercise research, PloS One source

      Not checked in the free run.

  • Classified as probably not a substantial claim. May combine two claims.

    Premisecitation

    Mitochondria are dynamic organelles, and the production of new mitochondrial proteins is an important determinant of their overall function.

    “Mitochondria are dynamic organelles, and the production of new mitochondrial proteins is an important determinant of their overall function [48].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [48] Miller, 2012, A perspective on the determination of mitochondrial biogenesis, American Journal of Physiology. Endocrinology and Metabolism source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    Both protein content of mitochondrial complex subunits and CS activity are valid markers of mitochondrial content.

    “There were no changes to the protein content of mitochondrial complex subunits or CS activity, both of which are valid markers of mitochondrial content [16].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [16] Larsen, 2012, Biomarkers of mitochondrial content in skeletal muscle of healthy young human subjects, Journal of Physiology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Exercise is known to acutely increase skeletal muscle Glut4 mRNA.

    “While exercise is known to acutely increase skeletal muscle Glut4 mRNA [22]”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [22] Richter, 2013, Exercise, GLUT4, and skeletal muscle glucose uptake, Physiological Reviews source

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Tissue availability for this project necessitated the use of sarcoplasmic protein synthetic rate (SarcPS) as a proxy for MitoPS.

    “However, tissue availability for this project necessitated the use of sarcoplasmic protein synthetic rate (e.g., SarcPS – Figure 5A) as a proxy for MitoPS.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductown data

    Because of insufficient muscle sample collections for one participant, only samples from seven participants in the NS group were prepared for RT-PCR.

    “Because of insufficient muscle sample collections for one participant, only samples from seven participants in the NS group were prepared for RT-PCR.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Interpretationreasoning

    It is plausible that GLUT4 translocation to the cell membrane may be impaired following sleep restriction, which would support previous research indicating impairments within the insulin signaling pathway.

    “Therefore, while no changes to Glut4 mRNA or protein content were observed in tandem with changes in glucose tolerance, it is plausible that GLUT4 translocation to the cell membrane may be impaired, which would support previous research that has indicated impairments within the insulin signaling pathway following sleep restriction [52,53].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [52] Broussard, 2012, Impaired insulin signaling in human adipocytes after experimental sleep restriction: a randomized, crossover study, Annals of Internal Medicine source

      Not checked in the free run.

    • cites [53] Sweeney, 2017, Skeletal muscle insulin signaling and whole-body glucose metabolism following acute sleep restriction in healthy males, Physics Reports

      Not checked in the free run.

  • Classified as probably not a substantial claim.

    Premisecitation

    Exercise can acutely influence markers of mitochondrial dynamics.

    “Considering that exercise can also acutely influence markers of mitochondrial dynamics [59], this suggests the chosen muscle sampling time points may not have been appropriate to detect these potential changes [51].”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites [59] Trewin, 2018, Exercise and mitochondrial dynamics: keeping in shape with ROS and AMPK, Antioxidants source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Endurance exercise is well known to increase mitochondrial content.

    “Despite no change in CS activity or protein content of mitochondrial complex subunits in the SR+EX group, endurance exercise is well known to increase mitochondrial content [25].”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [25] Holloszy, 1967, Biochemical adaptations in muscle. Effects of exercise on mitochondrial oxygen uptake and respiratory enzyme activity in skeletal muscle, Journal of Biological Chemistry source

      Not checked in the free run.

  • May combine two claims.

    Interpretationown data

    The results provide evidence supportive of a link between reduced mitochondrial respiratory function and impaired glucose tolerance, which was not observed in the SR+EX group.

    “Nonetheless, our results do provide evidence supportive of a link between reduced mitochondrial respiratory function and impaired glucose tolerance, which was not observed in the SR+EX group.”
    Quote in the paperSubstantial claim
    • Rests on an assumption: The observed changes in glucose tolerance, mitochondrial function, and diurnal rhythms are attributable to the sleep restriction intervention rather than to other uncontrolled factors.
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Martinez-Nicolas et al. demonstrated improved circadian temperature amplitude in response to a CPAP intervention.

    “In fact, similar to our study, Martinez-Nicolas et al. [63] demonstrated improved circadian temperature amplitude in response to a continuous positive airway pressure (CPAP) intervention, which suggests that physiological interventions can mitigate some circadian aspects of sleep disruption.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [63] Martinez-Nicolas, 2017, Circadian impairment of distal skin temperature rhythm in patients with sleep-disordered breathing: the effect of CPAP, Sleep source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Study design and conductreasoning

    The collection of muscle samples following an OGTT may have altered molecular signaling pathways, although no differences were observed between groups.

    “This may have altered molecular signaling pathways, although we did not observe any differences between the groups.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Exercise has potential benefits in the context of circadian misalignment and sleep loss.

    “Considering the negative metabolic consequences, such as reduction in insulin sensitivity and mitochondrial function, attributed to both circadian misalignment and sleep loss [21,67] and the potential benefits of exercise in this context [17,68], further research is warranted.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [17] Saner, 2018, Is exercise a viable therapeutic intervention to mitigate mitochondrial dysfunction and insulin resistance induced by sleep loss?, Sleep Medicine Reviews source

      Not checked in the free run.

    • cites [68] Saner, 2020, Exercise: it's only a matter of time, Journal of Physiology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Moller-Levet et al. reported reduced amplitude of circadian expression of core clock genes following seven nights of sleep restriction (6 h TIB each night) in human white blood cells.

    “Previously, Moller-Levet et al. [65] reported reduced amplitude of circadian expression of core clock genes following seven nights of sleep restriction (6 h TIB each night), in human white blood cells.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites [65] Moller-Levet, 2013, Effects of insufficient sleep on circadian rhythmicity and expression amplitude of the human blood transcriptome, Proceedings of the National Academy of Sciences of the U S A source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Premisecitation

    Others have reported exercise-induced changes in skeletal muscle clock gene expression, which is thought to be a time-of-day dependent effect.

    “While others have reported exercise-induced changes in skeletal muscle clock gene expression [32,66], this is thought to be a time-of-day dependent effect [66].”
    Quote in the paperNot a substantial claim0 of 2 sources checked
    • cites [32] Zambon, 2003, Time- and exercise-dependent gene regulation in human skeletal muscle, Genome Biology source

      Not checked in the free run.

    • cites [66] Kemler, 2020, Time-of-day dependent effects of contractile activity on the phase of the skeletal muscle clock, Journal of Physiology source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S3 (load-bearing). May combine two claims.

    Interpretationreasoning

    The contrast between our findings and Cedernaes et al. is potentially explained by differences in length and severity of sleep loss interventions and/or differences in participant numbers and statistical power.

    “This is potentially explained by the differences in length and severity of the sleep loss interventions and/or the difference in participant numbers and statistical power.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Premisecitation

    Negative metabolic consequences, such as reduction in insulin sensitivity and mitochondrial function, are attributed to both circadian misalignment and sleep loss.

    “Considering the negative metabolic consequences, such as reduction in insulin sensitivity and mitochondrial function, attributed to both circadian misalignment and sleep loss [21,67] and the potential benefits of exercise in this context [17,68], further research is warranted.”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites [21] Andrews, 2010, CLOCK and BMAL1 regulate MyoD and are necessary for maintenance of skeletal muscle phenotype and function, Proceedings of the National Academy of Sciences of the U S A source

      Not checked in the free run.

    • cites [67] Harfmann, 2016, Muscle-specific loss of Bmal1 leads to disrupted tissue glucose metabolism and systemic glucose homeostasis, Skeletal Muscle source

      Not checked in the free run.

  • Probably not a substantial claim: may not pass S2 (checkable), S3 (load-bearing).

    Study design and conductreasoning

    The inclusion of a normal sleep and exercise group (NS+EX) would have helped to elucidate the contribution of HIIE to prevent the negative metabolic consequences observed in the SR group.

    “Finally, the inclusion of a normal sleep and exercise group (NS+EX), would have helped to elucidate the contribution of HIIE to prevent the negative metabolic consequences observed in the SR group.”
    Quote in the paperNot a substantial claim
  • Classified as probably not a substantial claim.

    Study design and conductreasoning

    Because of the extremely challenging and invasive nature of the protocol, a parallel group design was chosen.

    “Because of the extremely challenging and invasive nature of the protocol, a parallel group design was chosen.”
    Quote in the paperSubstantial claim
  • Probably not a substantial claim: may not pass S3 (load-bearing).

    Study design and conductreasoning

    Muscle samples were collected following an OGTT to minimize any potential effect caused by the biopsy procedure on the participant's glycemic response.

    “Further, it is also important to note that muscle samples were collected following an OGTT to minimize any potential effect caused by the biopsy procedure on the participant's glycemic response.”
    Quote in the paperNot a substantial claim
  • Probably not a substantial claim: may not pass S2 (checkable).

    Interpretationown data

    These data provide a basis for the development of evidence-based health guidelines and recommendations for those experiencing inadequate sleep by highlighting some of the underlying biological mechanisms that can be targeted by therapeutic interventions such as exercise.

    “While further research is still required, these data provide a basis for the development of evidence-based health guidelines and recommendations for those experiencing inadequate sleep by highlighting some of the underlying biological mechanisms that can be targeted by therapeutic interventions such as exercise.”
    Quote in the paperNot a substantial claim
62 of 62
  • The paper relies on this without support.

    There are limited data explaining the physiological and molecular changes that underpin the effects of sleep loss on glucose metabolism.

    “Despite these findings, there are limited data explaining the physiological and molecular changes that underpin these effects.”
  • The paper relies on this without support.

    How results from 120 h of sleep deprivation translate to repeated nights of partial sleep loss commonly experienced in society has not been determined and remains a critical gap in the literature.

    “However, how these results translate to the context of the sleep loss commonly experienced in society, such as repeated nights of partial sleep loss, has not been determined and remains a critical gap in the literature.”
  • The paper relies on this without support.

    The effect of sleep restriction on markers of diurnal rhythms and the potential implications of such changes have not previously been examined.

    “However, the effect of sleep restriction on markers of diurnal rhythms (e.g., skeletal muscle clock gene expression) and the potential implications of such changes have not previously been examined.”
  • The paper relies on this without support.

    The physiological mechanisms that underpin the impairment of glucose tolerance following sleep restriction are likely multifactorial.

    “The physiological mechanisms that underpin the impairment of glucose tolerance following sleep restriction are likely multifactorial.”
  • The paper relies on this without support.

    The observed changes in glucose tolerance, mitochondrial function, and diurnal rhythms are attributable to the sleep restriction intervention rather than to other uncontrolled factors.

    “We discovered that in healthy young men, sleep restriction resulted in significantly impaired glucose tolerance, with concomitant changes in skeletal muscle mitochondrial respiratory function, sarcoplasmic protein synthesis (SarcPS) – a proxy for mitochondrial protein synthesis, and diurnal rhythms of peripheral skin temperature.”
  • The paper relies on this without support.

    SarcPS is a valid proxy for MitoPS.

    “However, tissue availability for this project necessitated the use of sarcoplasmic protein synthetic rate (e.g., SarcPS – Figure 5A) as a proxy for MitoPS.”
  • The paper relies on this without support.

    Peripheral skin temperature provides a physiological index of circadian output.

    “Peripheral skin temperature measures oscillate inversely to the rhythms of core body temperature, and therefore provides a physiological index of circadian output.”
7 of 7

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • Three HIIT sessions during a 5-day period of sleep restriction (4-h TIB) mitigated negative effects of sleep loss on circadian rhythmicity, glucose tolerance, skeletal muscle mitochondrial function, and sarcoplasmic protein synthesis in young healthy men aged 18-40 years.

    “Saner et al. conducted a study in 2021 showing that the incorporation of 3 high intensity interval training (HIIT) sessions during a 5-day period of sleep restriction (4-h TIB) mitigate the negative effects that sleep loss has on circadian rhythmicity, glucose tolerance, skeletal muscle mitochondrial function, and sarcoplasmic protein synthesis in young healthy men aged 18-40 years.”

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

Each contradiction between two passages listed here was confirmed by an independent check.

  • Exercise did not prevent the reported loss of skin-temperature rhythm amplitude

    Major

    The abstract says the detrimental effects were not observed with HIIE, but the results report a significant decrease in diurnal skin-temperature amplitude in the SR+EX group (P = 0.008), just as in the SR group.

  • Discussion gives the wrong SR Glut4 mRNA change

    Minor

    The discussion calls the SR group's Glut4 mRNA change 33%, whereas Table 2 gives its mean change as −38%; 33 is the table's standard deviation.

2 of 2

Cites

Flagged first, then by citations

4 of the 74 references couldn’t be matched to a known paper.

Cited by

Sorted by citations

Authors
Saner, N. J., Lee, M. J.-C., Kuang, J., Pitchford, N. W., Roach, G. D., Garnham, A., Genders, A. J., Stokes, T., Schroder, E. A., Huo, Z., Esser, K. A., Phillips, S. M., Bishop, D. J., & Bartlett, J. D.
Affiliations
  • Baker Heart and Diabetes Institute (AU)
  • Victoria University (AU)
  • University of Tasmania (AU)
  • Central Queensland University (AU)
  • McMaster University (CA)
  • University of Kentucky (US)
  • University of Florida (US)
Corresponding author
  • Saner, Nicholas J.
  • Bishop, David J.
Venue
Molecular Metabolism
Publisher
Elsevier BV
Published
2021-01
Volume
43
Pages
101110
ISSN
2212-8778 (ISSN-L)
OpenAlex
W3094703559
Cited by
68
References
74
Citations by year
2026: 6 · 2025: 12 · 2024: 19 · 2023: 9 · 2022: 17 · 2021: 4 · 2020: 1
FWCI
7.49
Type
journal article
Language
en
Open access
Locations
  • Molecular Metabolism (publishedVersion, cc-by-nc-nd)
  • bioRxiv (Cold Spring Harbor Laboratory) (acceptedVersion, cc-by-nc-nd)
  • PubMed Central (publishedVersion, cc-by-nc-nd)
  • PubMed (publishedVersion)
  • UTAS Research Repository (acceptedVersion)
  • Victoria University Research Repository (Victoria University) (submittedVersion, cc-by-nc-nd)
  • Deakin Research Online (Deakin University) (submittedVersion)
  • Figshare (submittedVersion, cc-by-nc-nd)
Funders
  • Sports Medicine Australia Research Foundation
  • Canada Research Chairs
Topics
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and related disorders
Keywords
sleep restriction, sleep deprivation, high-intensity interval exercise, glucose tolerance, impaired glucose tolerance, mitochondrial respiratory function, circadian rhythm, circadian misalignment, skeletal muscle protein synthesis, insulin sensitivity, young men, healthy young adults
MeSH terms
Adult, Blood Glucose, Circadian Rhythm, Exercise Therapy, Glucose, Glucose Tolerance Test, Humans, Male, Mitochondria, Sarcomeres, Sleep, Sleep Deprivation, Protein Biosynthesis, Exercise, Muscle Cells, Carbohydrate Metabolism, Healthy Volunteers

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Claims read by deepseek-v4.1-flash under definition version 3 (extract-v3) on 2026-10-06.

Classified by jev-1.13-20260917 (gold-guideline-v0.2) on 2026-10-06.

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