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Cited by 215Circadian rhythm and melatoninSleep and Work-Related FatigueHeart Rate Variability and Autonomic Control

The impact of the circadian timing system on cardiovascular and metabolic function

Open access
Morris, Christopher J., Yang, Jessica N., Scheer, Frank A.J.L.·2012·Progress in Brain Research
DOI 10.1016/b978-0-444-59427-3.00019-8PMC PMC3704149
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Abstract

Epidemiological studies show that adverse cardiovascular events peak in the morning (i.e., between 6 AM and noon) and that shift work is associated with cardiovascular disease, obesity, and diabetes. The endogenous circadian timing system modulates certain cardiovascular risk markers to be highest (e.g., cortisol, nonlinear dynamic heart rate control, and platelet activation) or to respond most unfavorably to stressors such as exercise (e.g., epinephrine, norepinephrine, and vagal cardiac modulation) at an internal body time corresponding to the time of day when adverse cardiovascular events most likely occur. This indicates that the circadian timing system and its interaction with external cardiovascular stressors (e.g., physical activity) could contribute to the morning peak in adverse cardiovascular events. Moreover, circadian misalignment and simulated night work have adverse effects on cardiovascular and metabolic function. This suggests that misalignment between the behavioral cycle and the circadian timing system in shift workers contributes to that population’s increased risk for cardiometabolic disease.

AI snapshot

Written from the paper’s full text.

TL;DR

This review synthesizes evidence that the endogenous circadian timing system modulates cardiovascular and metabolic risk markers, with some thrombotic markers peaking in the biological morning (6 AM–noon) and circadian misalignment/shift work adversely affecting blood pressure, glucose tolerance, and leptin. It argues that circadian disruption may contribute to the morning peak in adverse cardiovascular events and to shift workers’ increased cardiometabolic risk.

Key findings

  • Adverse cardiovascular events such as myocardial infarction, stroke, arrhythmias, and sudden cardiac death peak between approximately 6 AM and noon; shift work is associated with cardiovascular disease, obesity, and diabetes.
  • Platelet size and surface expression of activated GPIIb-IIIa, P-selectin, and GP1b are greatest during the biological morning, corresponding to 6 AM to noon, suggesting a circadian contribution to morning thrombotic risk; platelet count and aggregability peak at a circadian phase equivalent to 3–8 PM.
  • The circadian system causes blood pressure to peak during the biological evening, approximately 9 PM, and increases postprandial glucose and insulin responses while decreasing leptin during short-term circadian misalignment.
  • In animal models, circadian disruption worsens cardiovascular outcomes: cardiomyopathic hamsters subjected to weekly 12-h light/dark shifts have shorter lifespans, and Tau mutant hamsters on a 24-h light/dark cycle develop cardiomyopathy, fibrosis, and impaired heart contractility that are largely reversed on a 22-h cycle.

Methods

  • Narrative review of mammalian and human literature; no new primary data are presented.
  • Synthesizes epidemiological studies, human constant routine and forced desynchrony protocols, animal SCN lesion and clock-gene models, and simulated shift work/night work studies.
  • Main analysis is qualitative synthesis; no systematic search strategy, meta-analysis, or formal risk-of-bias assessment is described.

Limitations

  • Stated: previous work has been conducted in healthy people, and further research is needed in individuals at risk for adverse cardiovascular events to determine whether timing and amplitude of endogenous circadian rhythms in cardiovascular risk markers change.
  • Stated: more research is needed to fully understand mechanisms, and human studies on circadian misalignment or simulated night work and cardiovascular function are scarce.
  • Evident: as a narrative review, it does not systematically appraise study quality or quantify pooled effects, and many mechanistic findings come from animal models whose translation to humans remains uncertain.

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

Integrity signals

Registry

Crossref · 10.1016/b978-0-444-59427-3.00019-8

Cites

Statistics

Nothing to recompute.

Claims the paper makes

0 of 143 cited sources checked · 0 supported · 0 flagged

  • Findingcitation

    The circadian peak in blood pressure occurred during the biological evening, corresponding to approximately 9 PM.

    “The circadian peak in blood pressure occurred during the biological evening, corresponding to approximately 9 PM.”
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    • cites Shea et al., 2011 source

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  • Findingcitation

    The authors demonstrated a robust endogenous circadian rhythm in blood pressure in healthy humans, with very similar timing and amplitude across three different protocols.

    “recently, we demonstrated a robust endogenous circadian rhythm in blood pressure in healthy humans, with very similar timing and amplitude across three different protocols”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Shea et al., 2011 source

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  • Premisecitation

    A circadian rhythm in resting heart rate exists in healthy humans, with a broad peak during the middle of the biological day and a trough during the biological night.

    “A circadian rhythm in resting heart rate has been reported by different research groups in healthy humans, with a broad peak occurring during the middle of the biological day and a trough during the biological night”
    Quote in the paperSubstantial claim0 of 3 sources checked
    • cites Burgess et al., 1997 source

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    • cites Kräuchi and Wirz-Justice, 1994

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    • cites Scheer et al., 2010 source

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  • Interpretationreasoning

    Misalignment between the behavioral cycle and the circadian timing system in shift workers contributes to that population's increased risk for cardiometabolic disease.

    “This suggests that misalignment between the behavioral cycle and the circadian timing system in shift workers contributes to that population’s increased risk for cardiometabolic disease.”
    Quote in the paperSubstantial claim
  • Interpretationreasoning

    If the timing is similar in vulnerable populations, the circadian peak of catecholamines is unlikely to contribute to the morning peak in adverse cardiovascular events.

    “Therefore, if the timing would be similar in vulnerable populations, the circadian peak of catecholamines unlikely contributes to the morning peak in adverse cardiovascular events.”
    Quote in the paperNot a substantial claim
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    Premisecitation

    The reactivity of blood pressure to exercise, but not postural change, is controlled by the circadian timing system, with the greatest response occurring during the biological evening.

    “The reactivity of blood pressure to exercise, but not postural change, is also controlled by the circadian timing system, again with the greatest response occurring during the biological evening”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Hu et al., 2011

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    • cites Scheer et al., 2010 source

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    Interpretationreasoning

    The SCN has an inhibitory influence on resting heart rate during the biological day and an excitatory influence during the biological night.

    “This suggests that the SCN has an inhibitory and excitatory influence on resting heart rate during the biological day and night, respectively.”
    Quote in the paperSubstantial claim

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    Premisenone given

    Circadian misalignment and simulated night work have adverse effects on cardiovascular and metabolic function.

    “Moreover, circadian misalignment and simulated night work have adverse effects on cardiovascular and metabolic function.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The reactivity of platelet measures to mental, postural, and physical stress was not significantly influenced by the circadian timing system, and the influence of the circadian timing system and behavioral stressors appear additive.

    “The reactivity of the above platelet measures to mental, postural, and physical stress was not significantly influenced by the circadian timing system, and thus, the influence of the circadian timing system and that of behavioral stressors appear to be additive”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Scheer et al., 2011 source

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    Premisecitation

    Shift work is associated with cardiovascular disease, obesity, and diabetes.

    “shift work is associated with cardiovascular disease, obesity, and diabetes”
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    • cites Kawachi et al., 1995 source

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    • cites Knutsson et al., 1986 source

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    • cites Suwazono et al., 2008b

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    Premisecitation

    After lesioning the SCN, the circadian rhythm in resting heart rate is abolished and the level of resting heart rate is intermediate between that during the biological day and night in intact animals.

    “After lesioning the SCN, the circadian rhythm is abolished and the level of resting heart rate is intermediate between that during the biological day and night in intact animals.”
    Quote in the paperSubstantial claim

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    Interpretationcitation

    The morning peaks in epinephrine and norepinephrine reactivity coincide with the circadian peak in cortisol, which may further increase cardiac vulnerability because cortisol can potentiate the effects of the sympathetic nervous system.

    “These morning peaks coincide with the circadian peak in cortisol (Scheer et al., 2009, 2010; Wehr et al., 2001), which may further increase cardiac vulnerability since cortisol can potentiate the effects of the sympathetic nervous system (Davies and Lefkowitz, 1984).”
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    • cites Davies and Lefkowitz, 1984

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    Premisecitation

    The reactivity of epinephrine and norepinephrine in healthy humans to exercise is dependent on circadian phase, with two peaks: one in the biological morning and the other in the biological evening.

    “The reactivity of epinephrine and norepinephrine in healthy humans to exercise is dependent on circadian phase, with two peaks: one in the biological morning and the other in the biological evening”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Scheer et al., 2010 source

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    Premisecitation

    The circadian timing system influences the reactivity of the sympathetic nervous system to behavioral stressors, including exercise and passive head-up tilt, with the largest reduction in parasympathetic markers occurring in the biological morning, corresponding to approximately 9 AM.

    “The circadian timing system also influences the reactivity of the sympathetic nervous system to behavioral stressors, including exercise and passive head-up tilt, with the largest reduction in parasympathetic markers occurring in the biological morning, corresponding to approximately 9 AM”
    Quote in the paperSubstantial claim0 of 2 sources checked
    • cites Hu et al., 2011

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    • cites Scheer et al., 2010 source

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    Premisecitation

    The fractal pattern of heart beat variability breaks down with disease and its change is predictive of mortality.

    “This fractal pattern breaks down with disease and its change is predictive of mortality”
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    • cites Hu et al., 2009

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    • cites Mäkikallio et al., 2004 source

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    • cites Peng et al., 1995 source

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

    Premisecitation

    Examples of circadian clock gene mutations that impact circadian function include familial advanced sleep phase syndrome in humans and many clock gene mutations in experimental animals.

    “Examples of circadian clock gene mutations which impact circadian function include familial advanced sleep phase syndrome in humans and the many clock gene mutations in experimental animals”
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    • cites Toh et al., 2001 source

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    • cites Turek et al., 2005 source

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    Premisecitation

    In mice, 45 min of experimenter-induced ischemia of the coronary artery at the beginning of the biological night, compared with the start of the biological day, resulted in greater infarct volume, fibrosis, adverse remodeling, and depression of contractile function after 1 month of reperfusion.

    “A recent study in mice demonstrated that 45 min of experimenter-induced ischemia of the coronary artery at the beginning of the biological night (start of the active phase, thus equivalent to the human morning) as compared to the start of the biological day resulted in greater infarct volume, fibrosis, adverse remodeling, and depression of contractile function after 1 month of reperfusion”
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    • cites Durgan et al., 2010 source

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    Premisecitation

    Lesioning of the SCN abolishes fractal patterns in heart beat variability at time scales between 4 and 24 h, rendering the pattern similar to random noise and demonstrating the SCN as a critical node in the neural feedback network underlying scale-invariant patterns in physiology.

    “lesioning of the SCN abolishes such fractal patterns in heart beat variability at time scales between 4 and 24 h, rendering the pattern similar to random noise and demonstrating the SCN as a critical node in the neural feedback network underlying scale-invariant patterns in physiology”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Hu et al., 2008

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    Premisecitation

    Markers of parasympathetic nervous activity display a circadian rhythm at rest in healthy humans, with peaks in the biological night and morning, and may be protective in the morning in healthy subjects at rest.

    “Markers of parasympathetic nervous activity display a circadian rhythm at rest in healthy humans, with peaks in the biological night and morning, and thus may be “protective” in the morning, at least in healthy subjects at rest”
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    • cites Burgess et al., 1997 source

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    • cites Hu et al., 2011

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    Premisecitation

    Circadian disruption with underlying neuroanatomical changes in the SCN has been demonstrated in Alzheimer's disease and depression.

    “Circadian disruption with underlying neuroanatomical changes in the SCN has been demonstrated in Alzheimer’s disease and depression”
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    • cites Wu et al., 2006

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    • cites Zhou et al., 2001 source

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    Premisecitation

    Tau mutant hamsters living on a 24-h light/dark cycle have cardiomyopathy, fibrosis, and impaired heart contractility.

    “Tau mutant hamsters have a shorter life span and have cardiomyopathy, fibrosis, and impaired heart contractility when they live on a 24-h light/dark cycle which is beyond their circadian timing system’s range of entrainment and thus causes the animal’s behavioral cycle and biological timing system to be out of phase (i.e., desynchronized; Martino et al., 2008).”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Martino et al., 2008 source

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    Premisecitation

    Mice with surgically induced heart disease that live on an abnormal light/dark (10:10 h) cycle after surgery show impaired compensatory cardiac and vascular remodeling, reduced ventricular contractile strength, and increased blood pressure compared with animals on a normal light/dark (12:12 h) cycle.

    “mice with surgically induced heart disease (cardiac hypertrophy through transverse aortic constriction) that live on an abnormal light/dark (10:10 h) cycle following surgery show impaired compensatory cardiac and vascular remodeling, reduced ventricular contractile strength, and increased blood pressure as compared to animals that live on a normal light/dark (12:12 h) cycle”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Martino et al., 2007 source

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    Interpretationreasoning

    The circadian timing system is an important entity that contributes to the control of many metabolic-related processes, and thus circadian disruption may result in impaired metabolic function.

    “Taken together, the circadian timing system is an important entity that contributes to the control of many metabolic-related processes, and thus it is conceivable that circadian disruption results in impaired metabolic function.”
    Quote in the paperSubstantial claim

  • Probably not a substantial claim: may not pass S3 (load-bearing), S4 (based).

    Interpretationreasoning

    The hypertension in Cry-null mice on a salt diet may have been due to overexcretion of aldosterone, which increases blood pressure through stimulation of reabsorption of sodium ions and water.

    “This finding may have been due to Cry-null mice overexcreting the hormone aldosterone which increases blood pressure through stimulation of reabsorption of sodium ions and water.”
    Quote in the paperNot a substantial claim

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    Premisecitation

    Mice without core clock components Cry1 and Cry2 develop hypertension when their diet contains salt, whereas wild-type mice do not.

    “Mice without core clock components Cry1 and Cry2 develop hypertension when their diet contains salt, whereas wild-type mice do not (Doi et al., 2010).”
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    • cites Doi et al., 2010 source

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    Premisecitation

    Mice lacking the Clock gene specifically within cardiomyocytes have brachycardia, greater myocardial oxygen consumption, and decreased cardiac efficiency.

    “Moreover, mice lacking the Clock gene specifically within cardiomyocytes have brachycardia, greater myocardial oxygen consumption, and decreased cardiac efficiency (Bray et al., 2008).”
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    • cites Bray et al., 2008 source

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    Premisecitation

    Repeated nighttime melatonin administration enhanced the day/night rhythm amplitude of blood pressure and reduced blood pressure during the patient's scheduled sleep period in patients with essential hypertension.

    “Repeated nighttime melatonin administration enhanced the day/night rhythm amplitude of blood pressure and reduced blood pressure during the patient’s scheduled sleep period.”
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    • cites Scheer et al., 2004 source

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    Interpretationreasoning

    Reduced levels of vasopressin in the SCN could result in disinhibition of CRH production by the PVN and contribute to the abnormal 24-h variation in blood pressure observed in hypertensive patients.

    “Thus, the reduced levels of vasopressin in the SCN could result in disinhibition of CRH production by the PVN and, in turn, contribute to the abnormal 24-h variation in blood pressure observed in these patients (Goncharuk et al., 2002).”
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    • cites Goncharuk et al., 2002 source

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    Interpretationcitation

    The improvement in blood pressure after 3 weeks of melatonin intake was not due to the drug's acute vasodilatory effect but possibly a result of its influence on the circadian timing system.

    “Of interest, acute nighttime melatonin intake did not influence blood pressure indicating that the improvement in blood pressure after 3 weeks of melatonin intake was not due to the drugs acute vasodilatory effect but possibly a result of its influence on the circadian timing system.”
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    • cites Scheer et al., 2004 source

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    Premisecitation

    Integrated glucose (statistical trend) and triglyceride levels were higher across the night shift than day shift.

    “The researchers reported that integrated glucose (statistical trend) and triglyceride levels were higher across the night shift than day shift.”
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    • cites Al-Naimi et al., 2004 source

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    Premisecitation

    Homozygous ClockΔ19 mutant mice exhibit adipocyte hypertrophy, lipid enlargement of hepatocytes with pronounced glycogen build-up, hypercholesterolemia, hypertriglyceridemia, hypoinsulinemia, and hyperglycemia.

    “In addition, they exhibit adipocyte hypertrophy, lipid enlargement of hepatocytes with pronounced glycogen build-up, hypercholesterolemia, hypertriglyceridemia, hypoinsulinemia, and hyperglycemia.”
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    • cites Turek et al., 2005 source

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    Premisecitation

    Homozygous ClockΔ19 mutant (C57BL/6J) mice have a significantly attenuated diurnal feeding rhythm and are hyperphagic and obese compared to wild-type mice.

    “Homozygous ClockΔ19 mutant (C57BL/6J) mice have a significantly attenuated diurnal feeding rhythm and are hyperphagic and obese compared to wild-type mice (Turek et al., 2005).”
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    • cites Turek et al., 2005 source

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    Interpretationcitation

    The increases in body fat percentage and body mass in mice fed during biological day may have been due to lower energy expended via physical activity and greater food intake, although neither observation reached statistical significance.

    “These increases may have been due to lower energy expended via physical activity and greater food intake in the mice fed during the biological day, although neither of these observations reached statistical significance.”
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    • cites Arble et al., 2009 source

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    Interpretationcitation

    The night worker rats were less active, which may explain their greater body mass gain.

    “Total daily food intake did not differ between the two groups, but the “night workers” were less active and this may explain the above finding.”
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    • cites Salgado-Delgado et al., 2008 source

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    Premisecitation

    Feeding rodents only during the rest phase can phase shift peripheral oscillators in the liver, pancreas, kidney, and heart while having no effect on the phase of the SCN.

    “Feeding rodents only during the rest phase—as similarly occurs during night work when they eat during their night shift—can phase shift peripheral oscillators in the liver, pancreas, kidney, and heart while it has no effect on the phase of the SCN (Damiola et al., 2000; Stokkan et al., 2001).”
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    • cites Damiola et al., 2000 source

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    • cites Stokkan et al., 2001 source

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    Premisecitation

    The circadian phase angle at the time of the LPS challenge was similar between shifted and control animals, and therefore the findings were not due to the stimulus being given at a different circadian time.

    “The circadian phase angle, as assessed by body temperature; locomotor activity; and Per2 expression in four tissues (SCN, liver, thymus, and spleen), at the time of the LPS challenge was similar between the shifted and control animals, and therefore the findings were not due to the stimulus being given at a different circadian time between the two groups.”
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    • cites Castanon-Cervantes et al., 2010 source

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    Premisecitation

    Feeding mice for 6 weeks only during their biological day rather than biological night increases their body fat percentage (statistical trend) and body mass.

    “Moreover, feeding mice for 6 weeks only during their biological day (normal rest phase) rather than biological night (normal active phase) increases their body fat percentage (statistical trend) and body mass (Arble et al., 2009).”
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    • cites Arble et al., 2009 source

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    Premisecitation

    Glucose-stimulated insulin secretion is reduced in isolated pancreatic islets from Clock mutants, which may explain the observed impaired glucose tolerance in these animals.

    “The researchers also demonstrated that glucose-stimulated insulin secretion is reduced in isolated pancreatic islets from Clock mutants, which may explain the observed impaired glucose tolerance in these animals.”
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    • cites Marcheva et al., 2010 source

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    Interpretationcitation

    Some-but not all-of the adverse metabolic and hormonal effects of night work quickly subside after short-term exposure.

    “The glucose and insulin, but not triglyceride, postprandial responses normalize 2 days after ceasing night work, indicating that some—but not all—of the adverse metabolic and hormonal effects of night work quickly subside after short-term exposure (Lund et al., 2001; Ribeiro et al., 1998).”
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    Premisecitation

    Short-term exposure (after 3 days) to circadian misalignment per se increases postprandial responses of glucose and insulin, demonstrating reduced glucose tolerance and suggesting reduced insulin sensitivity.

    “Scheer et al. (2009), utilizing a forced desynchrony protocol, demonstrated that short-term exposure (after 3 days) to circadian misalignment per se increases the postprandial responses of glucose and insulin, demonstrating reduced glucose tolerance and suggesting reduced insulin sensitivity under these conditions (Fig. 4).”
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    • cites Scheer et al., 2009 source

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    Premisecitation

    Exposing mice to light (150 lux of continuous light or 16:8 150/5 lux cycle) during the habitual dark phase significantly increases body and fat mass and impairs glucose tolerance.

    “Exposing mice to light (150 lux of continues light or 16:8 150/5 lux cycle) during the habitual dark phase significantly increases body and fat mass and impairs glucose tolerance (Fonken et al., 2010).”
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    • cites Fonken et al., 2010 source

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    Premisecitation

    Both night work and circadian misalignment decrease total sleep time, which also decreases leptin levels and impairs glucose tolerance and insulin sensitivity.

    “Both night work and circadian misalignment decrease total sleep time which also decreases leptin levels and impairs glucose tolerance and insulin sensitivity (Åkerstedt, 1998; Buxton et al., 2010; Ohayon et al., 2002; Spiegel et al., 1999, 2004).”
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    • cites Åkerstedt, 1998 source

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    Premisecitation

    Restricting food intake in rodents to the biological night during simulated night work prevents the gain in body mass and the accumulation of abdominal fat deposits induced by such a work schedule; perhaps by preventing internal desynchrony.

    “Recent work has demonstrated that restricting food intake in rodents to the biological night (typical active period) undertaking simulated night work prevents the gain in body mass and the accumulation of abdominal fat deposits induced by such a work schedule; perhaps by preventing internal desynchrony (Salgado-Delgado et al., 2010).”
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    • cites Salgado-Delgado et al., 2010 source

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    Premisecitation

    Morning exercise can suppress daytime hunger and levels of acylated ghrelin.

    “Morning exercise can suppress daytime hunger and levels of acylated ghrelin (Broom et al., 2007).”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Broom et al., 2007 source

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    Premisecitation

    In mice, genetic elimination of Cry increases the expression of genes responsible for hepatic glucogenesis and also raises fasting blood glucose level.

    “In mice, genetic elimination of Cry increases the expression of genes responsible for hepatic glucogenesis and also raises fasting blood glucose level (Zhang et al., 2010).”
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    • cites Zhang et al., 2010 source

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    Premisereasoning

    mPer2−/− mice were hyperphagic under a high-fat diet and this may explain why these animals became obese.

    “These mice were also hyperphagic under a high-fat diet and this may explain why these animals became obese.”
    Quote in the paperSubstantial claim

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    Interpretationreasoning

    Core clock genes participate in the regulation of metabolic processes and many of the phenotypes induced by dysfunctional/lost clock genes are hallmarks of metabolic syndrome.

    “The above studies indicate that core clock genes participate in the regulation of metabolic processes and many of the phenotypes induced by dysfunctional/lost clock genes are hallmarks of metabolic syndrome.”
    Quote in the paperSubstantial claim

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    Interpretationnone given

    At rest, the circadian timing system causes some factors to peak during the biological morning (e.g., cortisol, platelet expression of activated GPIIb-IIIa, P-selectin, and GP1b), which could potentiate the onset of adverse cardiovascular events at that time.

    “At rest, the circadian timing system causes some factors to peak during the biological morning (e.g., cortisol, platelet expression of activated GPIIb-IIIa, P-selectin, and GP1b), which could potentiate the onset of adverse cardiovascular events at that time.”
    Quote in the paperSubstantial claim

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    Premisecitation

    The loss of Bmal1 in the liver of mice leads to hypoglycemia and to a loss of rhythmic expression of hepatic genes that regulate glucose homeostasis.

    “The loss of Bmal1 in the liver of mice leads to hypoglycemia and to a loss of rhythmic expression of hepatic genes that regulate glucose homeostasis (Lamia et al., 2008).”
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    • cites Lamia et al., 2008 source

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    Premisecitation

    Young pancreas-specific Bmal1 mutant mice showed increased ad libitum glucose levels, impaired glucose tolerance, lowered insulin secretion, and decreased insulin responsiveness to glucose.

    “In recent work, young pancreas-specific Bmal1 mutant mice showed increased ad libitum glucose levels, impaired glucose tolerance, lowered insulin secretion, and decreased insulin responsiveness to glucose (Marcheva et al., 2010).”
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    • cites Marcheva et al., 2010 source

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    Premisecitation

    Evening exercise increased levels of both acylated ghrelin and leptin but had no influence on mean hunger ratings during simulated night work.

    “Evening exercise increased levels of both acylated ghrelin and leptin but had no influence on mean hunger ratings.”
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    • cites Morris et al., 2010 source

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    Premisecitation

    The hypoglycemic response following insulin administration is exacerbated in Clock mutant and Bmal1−/− mice as compared in wild-type mice, possibly due to an impaired counterregulatory gluconeogenesis response.

    “The hypoglycemic response following insulin administration is exacerbated in Clock mutant and Bmal1−/− mice as compared in wild-type mice, possibly due to an impaired counterregulatory gluconeogenesis response (Rudic et al., 2004).”
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    • cites Rudic et al., 2004 source

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    Premisecitation

    The presence of high Bmal1 mRNA levels in adipocytes increased lipogenesis activity, further suggesting that Bmal1 is involved in regulating lipid metabolism.

    “The presence of high Bmal1 mRNA levels in adipocytes increased lipogenesis activity, further suggesting that Bmal1 is involved in regulating lipid metabolism.”
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    • cites Shimba et al., 2005 source

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    Premisecitation

    Participant's activity, as measured by a wrist accelerometer, was higher during the simulated night shift that was preceded by exercise, which could have beneficial implications for their energy balance.

    “Participant’s activity—as measured by a wrist accelerometer—was higher during the simulated night shift that was preceded by exercise which could have beneficial implications for their energy balance.”
    Quote in the paperNot a substantial claim0 of 1 sources checked
    • cites Morris et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisecitation

    These pancreas-specific Bmal1 mutant mice had normal body weight, activity, and feeding rhythms, suggesting that the above mentioned phenotypes are attributable to pancreatic clock disruption per se rather than to secondary changes in behavior.

    “These mice had normal body weight, activity, and feeding rhythms, suggesting that the above mentioned phenotypes are attributable to pancreatic clock disruption per se rather than to secondary changes in behavior.”
    Quote in the paperSubstantial claim0 of 1 sources checked
    • cites Marcheva et al., 2010 source

      Not checked in the free run.

  • May combine two claims.

    Premisenone given

    The circadian timing system causes the greatest increase in epinephrine level and the largest decrease in parasympathetic nervous activity in response to exercise to occur in the biological morning.

    “Moreover, the circadian timing system causes the greatest increase in epinephrine level and the largest decrease in parasympathetic nervous activity in response to exercise to occur in the biological morning.”
    Quote in the paperNot a substantial claim
51 of 51

  • The paper relies on this without support.

    Differences in socioeconomic status and lifestyle cannot fully explain the association between shift work and cardiovascular disease.

    “Because differences in socioeconomic status and life style cannot fully explain these observations”

  • The paper relies on this without support.

    Human studies investigating the effect of circadian misalignment or simulated night work on cardiovascular function in controlled laboratory conditions are scarce.

    “Human studies investigating the effect of circadian misalignment or simulated night work on cardiovascular function in controlled laboratory conditions are scarce.”

  • The paper relies on this without support.

    Findings from animal models of circadian disruption (such as Tau mutant hamsters and mice) can be generalized to humans, including individuals with preexisting heart disease.

    “Taken together, the above mentioned findings suggest that circadian disruption, such as with shift work, may worsen cardiovascular function in individuals with preexisting heart disease.”
3 of 3

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?

  • Shift work is a risk factor for diabetes, obesity, and cardiovascular disease.

    “Shift work is a risk factor for diabetes, obesity, and cardiovascular disease (63)(64)(65)(66).”

    From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [63]

  • Chrononutrition may be an important tool to enhance the metabolic health of the general population and to benefit the health of particular population groups (e.g., shift workers) and treatment of certain metabolic diseases.

    “In conclusion, evidence to date suggests that chrononutrition may be an important tool, not only to enhance the metabolic health of the general population but also to benefit the health of particular population groups (e.g., shift workers) and treatment of certain metabolic diseases.”

    From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [63]

  • Circadian organization is a clinically significant factor in the pathophysiology of metabolic diseases and in potential targeted strategies for treating them.

    “Given the growing body of evidence linking the circadian clock system to energy regulation and metabolic physiology, circadian organization emerges as a clinically significant factor that should be considered in the understanding of the pathophysiology of these diseases and in potential targeted strategies for treating them (49,63,81).”

    From Circadian rhythms, metabolism, and chrononutrition in rodents and humans (2016) · cites this paper as [63]

The citation lists haven’t been fetched yet

References 173 · Cited by 215

Authors
Morris, C. J., Yang, J. N., & Scheer, F. A. J. L.
Affiliations
Brigham and Women's Hospital (US)
Corresponding author
Morris, Christopher J.
ORCID
Scheer, Frank A.J.L.
Venue
Progress in Brain Research
Publisher
Elsevier
Published
2012
Volume
199
Pages
337-358
ISSN
0079-6123 (ISSN-L)
DOI
10.1016/b978-0-444-59427-3.00019-8
PMC
PMC3704149
OpenAlex
W1481045036
Semantic Scholar
aadc8701fef383355211f401b27451029b74bc1f
Cited by
215
References
173
Citations by year
2026: 15 · 2025: 12 · 2024: 9 · 2023: 15 · 2022: 15 · 2021: 13 · 2020: 15 · 2019: 15 · 2018: 20 · 2017: 16 · 2016: 20 · 2015: 21 · 2014: 15 · 2013: 13 · 2012: 1
FWCI
17.37
Type
book chapter
Language
en
Open access
Licence
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations
  • Progress in brain research (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Aeronautics and Space Administration
  • National Space Biomedical Research Institute
  • National Institutes of Health
  • Centers for Disease Control and Prevention
  • National Heart, Lung, and Blood Institute (R01HL094806, P30HL101299)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
  • Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
  • Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Heart Rate Variability and Autonomic Control
Keywords
circadian system, cardiovascular risk, metabolic function, shift work, circadian misalignment, cortisol, heart rate variability, platelet activation, exercise stress response, cardiometabolic disease
MeSH terms
Animals, Cardiovascular Diseases, Humans, Metabolic Diseases, Chronobiology Disorders, Circadian Clocks

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