The Meter of Metabolism
Open accessAbstract
The circadian system orchestrates the temporal organization of many aspects of physiology, including metabolism, in synchrony with the 24 hr rotation of the Earth. Like the metabolic system, the circadian system is a complex feedback network that involves interactions between the central nervous system and peripheral tissues. Emerging evidence suggests that circadian regulation is intimately linked to metabolic homeostasis and that dysregulation of circadian rhythms can contribute to disease. Conversely, metabolic signals also feed back into the circadian system, modulating circadian gene expression and behavior. Here, we review the relationship between the circadian and metabolic systems and the implications for cardiovascular disease, obesity, and diabetes.
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The term chrono-nutrition was introduced in 1986 by Delabois but was not much used beyond its application in weight loss diets.
“The term chrono-nutrition was introduced in 1986 by Delabois (10) but was not much used beyond its application in weight loss diets.”
From Meal irregularity and cardiometabolic consequences: results from observational and intervention studies (2016) · cites this paper as [10]
Each endpoint was adjusted for age and regularly updated information on alcohol consumption, physical exercise, multivitamin use, menopausal status and postmenopausal hormone use, physical examination in the past 2 years, healthy eating score, smoking status, pack-years, and BMI.
“Each endpoint was adjusted for age and regularly updated information throughout follow-up on: alcohol consumption, physical exercise, multivitamin use, menopausal status and postmenopausal hormone use, physical examination in the past 2 years, healthy eating score37 (without components of multivitamin and alcohol, which were adjusted individually), smoking status, pack-years, and BMI.”
From Total and Cause-Specific Mortality of U.S. Nurses Working Rotating Night Shifts (2015) · cites this paper as [37]
The circadian system and its prime marker, melatonin, are considered to have antitumor effects through multiple pathways, including antioxidant activity, anti-inflammatory effects, and immune enhancement.
“The circadian system and its prime marker, melatonin, are considered to have antitumor effects through multiple pathways, including antioxidant activity, anti-inflammatory effects, and immune enhancement.33-37”
From Total and Cause-Specific Mortality of U.S. Nurses Working Rotating Night Shifts (2015) · cites this paper as [37]
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The dorsomedial hypothalamic nucleus as a putative food-entrainable circadian pacemaker
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SCN Efferents to Peripheral Tissues: Implications for Biological Rhythms
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Self-citationDifferential expression of mRNA for leptin receptor isoforms in the rat brain
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Ghrelin Effects on the Circadian System of Mice
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The nuclear receptors Rev-erbs and RORs integrate circadian rhythms and metabolism
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Circulating Triglycerides Impact on Orexigenic Peptides and Neuronal Activity in Hypothalamus
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Self-citationFOXO and insulin signaling regulate sensitivity of the circadian clock to oxidative stress
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A Role for Brain-Specific Homeobox Factor Bsx in the Control of Hyperphagia and Locomotory Behavior
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Peripheral Circadian Clocks in the Vasculature
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A daily palatable meal without food deprivation entrains the suprachiasmatic nucleus of rats
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Immediate early response of the circadian polyA ribonuclease nocturnin to two extracellular stimuli
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Self-citationStudy of shift work and risk of coronary events
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Search for the feeding-entrainable circadian oscillator: a complex proposition
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Self-citationAttenuated feeding responses to circadian and palatability cues in mice lacking neuropeptide Y
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Dibner, C., Schibler, U., & Albrecht, U. (2010) · Annual Review of Physiology · doi:10.1146/annurev-physiol-021909-135821 · Cited by 2,421 · see citing works
Central and Peripheral Circadian Clocks in Mammals
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“Circadian control of metabolism occurs at the central (SCN) as well as local levels and involves clocks within a number of peripheral tissues including the liver, pancreas, skeletal muscle, intestine, and adipose tissue (for a review, see Bass & Takahashi 2010, Green et al. 2008).”
Self-citationDisruption of the clock components CLOCK and BMAL1 leads to hypoinsulinaemia and diabetes
Marcheva, B., Ramsey, K. M., Buhr, E. D., Kobayashi, Y., Su, H., Ko, C. H., Ivanova, G., Omura, C., Mo, S., Vitaterna, M. H., et al. (2010) · Nature · doi:10.1038/nature09253 · Cited by 1,525 · see citing works
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“The circadian clock also regulates energy homeostasis [16], and its disruption—as with social jetlag—may contribute to weight-related pathologies [17–19].”
Circadian Control of the NAD <sup>+</sup> Salvage Pathway by CLOCK-SIRT1
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Circadian control of the immune system
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Physiology of Circadian Entrainment
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CREB and the CRTC co-activators: sensors for hormonal and metabolic signals
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“In addition to being regulated by the effects of fasting and feeding hormones, hepatic gluconeogenesis is subject to regulation by the circadian clock, which coordinates hepatic metabolism with changes in the external environmen”
The Circadian Clock and Human Health
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AMPK regulates the circadian clock by cryptochrome phosphorylation and degradation
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Regulation of circadian behaviour and metabolism by synthetic REV-ERB agonists
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Self-citationMolecular components of the mammalian circadian clock
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“disorders, circadian clocks are also directly linked with feeding and cellular metabolism, and a number of metabolic complications may result from miscommunication with the circadian clock and metabolic pathways (Green et al. 2008).”
InfluentialSelf-citationSirtuin 1 and Sirtuin 3: Physiological Modulators of Metabolism
Nogueiras, R., Habegger, K. M., Chaudhary, N., Finan, B., Banks, A. S., Dietrich, M. O., Horváth, T. L., Sinclair, D. A., Pfluger, P. T., & Tschöp, M. H. (2012) · Physiological Reviews · doi:10.1152/physrev.00022.2011 · Cited by 712 · see citing works
“SIRT1 is expressed in the SCN, next to the ubiquitously expressed CLOCK, BMAL1, and all other components of the circadian machinery (119).”
A circadian rhythm orchestrated by histone deacetylase 3 controls hepatic lipid metabolism
Feng, D., Liu, T., Sun, Z., Bugge, A., Mullican, S. E., Alenghat, T., Liu, X. S., & Lazar, M. A. (2011) · Science · doi:10.1126/science.1198125 · Cited by 701 · see citing works
Shift work and chronic disease: the epidemiological evidence
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“Such metabolic disturbances may lead to the clinical expression of a number of comorbidities including central obesity, hypertension, dyslipidemia and endothelial dysfunction, all components of the metabolic syndrome and risk factors for CVD [8,76].”
Crosstalk between components of circadian and metabolic cycles in mammals
Asher, G., & Schibler, U. (2011) · Cell Metabolism · doi:10.1016/j.cmet.2011.01.006 · Cited by 601 · see citing works
Jakubowicz, D., Barnea, M., Wainstein, J., & Froy, O. (2013) · Obesity · doi:10.1002/oby.20460 · Cited by 593 · see citing works
“As the circadian clock and metabolism are tightly linked (12), and disruption of circadian rhythms leads to”
Cryptochromes mediate rhythmic repression of the glucocorticoid receptor
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“The methods section provides detailed information about all experimental procedures including (1) the generation, culture, and transfection of cell lines (2) generation or sources of plasmids and antibodies, (3) luciferase assays, (4) preparation of samples for western blotting, immunoprecipitation and chromatin immun…”
Rhythmicity of the intestinal microbiota is regulated by gender and the host circadian clock
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“Organisms adapted to this cycle by developing a circadian rhythm, an endogenous and entrainable mechanism that times daily events such as feeding, temperature, sleep-wakefulness, hormone secretion, and metabolic homeostasis (13, 14).”
REV-ERB and ROR nuclear receptors as drug targets
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Melatonin, energy metabolism, and obesity: a review
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Genetics of Circadian Rhythms in Mammalian Model Organisms
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“Instead, we refer the reader to several recent comprehensive treatments of this specific topic (Green et al., 2008; Bass and Takahashi, 2010; Maury et al., 2010; Asher and Schibler, 2011).”
Self-citationCryptochrome mediates circadian regulation of cAMP signaling and hepatic gluconeogenesis
Zhang, E. E., Liu, Y., Dentin, R., Pongsawakul, P. Y., Liu, A. C., Hirota, T., Nusinow, D. A., Sun, X., Landais, S., Kodama, Y., et al. (2010) · Nature Medicine · doi:10.1038/nm.2214 · Cited by 567 · see citing works
“Although the underlying mechanism is unclear, hepatic gluconeogenesis is also regulated by the circadian clock, which coordinates glucose metabolism with changes in the external environmen”
Metabolism and cancer: the circadian clock connection
Sahar, S., & Sassone-Corsi, P. (2009) · Nature Reviews Cancer · doi:10.1038/nrc2747 · Cited by 551 · see citing works
“This idea is particularly relevant as emerging evidence has revealed tight links between the molecular clock and the regulation of cellular metabolis”
Adrenergic Nerves Govern Circadian Leukocyte Recruitment to Tissues
Scheiermann, C., Kunisaki, Y., Lucas, D., Chow, A. T., Jang, J.-E., Zhang, D., Hashimoto, D., Mérad, M., & Frenette, P. S. (2012) · Immunity · doi:10.1016/j.immuni.2012.05.021 · Cited by 535 · see citing works
“This finding, along with the involvement of BMAL-1, strongly indicates genuine circadian rhythms and suggests their central orchestration by the molecular clock (Dibner et al., 2010; Green et al., 2008).”
Effect of sleep deprivation on the human metabolome
Davies, S. K., Ang, J. E., Revell, V. L., Holmes, B., Mann, A., Robertson, F. P., Cui, N., Middleton, B., Ackermann, K., Kayser, M., et al. (2014) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1402663111 · Cited by 527 · see citing works
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“…process tightly regulated by the clock system is metabolism (Asher and Schibler, 2011; Bass and Takahashi, 2010; Gerhart-Hines and Lazar, 2015; Green et al., 2008; Rutter et al., 2002), as both metabolites (Eckel-Mahan et al., 2012) and metabolic gene expression (Yang et al., 2006; Zhang et…”
Self-citationMetabolism and Circadian Rhythms—Implications for Obesity
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Mammalian circadian clock and metabolism – the epigenetic link
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SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket
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InfluentialTemporal orchestration of circadian autophagy rhythm by C/EBPβ
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Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure
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Cracking the O-GlcNAc code in metabolism
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Clock is important for food and circadian regulation of macronutrient absorption in mice
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“T circadian clock in the suprachiasmatic nucleus (SCN) of the hypothalamus regulates daily rhythms in behavior and physiology, ensuring that metabolic pathways are temporally coordinated with 24-h cycles of rest–activity and feeding (1).”
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“Bmal1/Clock also transactivate many other genes to regulate metabolism (5, 10).”
Circadian Rhythm of Redox State Regulates Excitability in Suprachiasmatic Nucleus Neurons
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Circadian Disruption Changes Gut Microbiome Taxa and Functional Gene Composition
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“…rhythms strongly control metabolic processes and inflammation responses, and exposure to light at night can disrupt the timing of these processes (Green et al., 2008; Asher and Schibler, 2011; Eckel-Mahan and SassoneCorsi, 2013; Fonken et al., 2013; Thaiss et al., 2014; Voigt et al., 2016).”
InfluentialClock Regulation of Metabolites Reveals Coupling between Transcription and Metabolism
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“shift work or jet lag) disrupt clock function and can cause sleep disorders, cancer, cardiovascular, and metabolic diseases (Asher and Schibler, 2011; Bass and Takahashi, 2010; Green et al., 2008).”
InfluentialBMAL1-dependent regulation of the mTOR signaling pathway delays aging
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“The circadian clock controls glucose and lipid homeostasis [14], cell redox state regulation [15], cell cycle [16] and genotoxic stress response [17].”
Human blood metabolite timetable indicates internal body time
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Total and Cause-Specific Mortality of U.S. Nurses Working Rotating Night Shifts
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“19 33-37 They also exhibit beneficial actions on cardiovascular health by enhancing endothelial function, maintaining metabolic homeostasis, 38 and reducing inflammation.”
Neutrophils in acute inflammation: current concepts and translational implications
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“90,91 Although circadian rhythms, in general, have long been known, 92,93 and clinical observations highlight the time-of-day variability in in fl ammatory-disease presentations, 94-96 therapeutic and clinical approaches (eg, scheduling of surgeries/interventions) incorporating this knowledge remain…”
The Mammalian Circadian Timing System and the Suprachiasmatic Nucleus as Its Pacemaker
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“For example, hypoxia inducible factor 1 (HIF1), PRDX-dependent redox changes, NAD+-dependent sirtuins and haem (a co-factor to nuclear receptors) all influence the TTFL, supporting the view that the entire cell comprises a higher-level circadian time-keeper, with intermeshed and mutually supportive TTFL and metabolic/…”
Noninvasive method for assessing the human circadian clock using hair follicle cells
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Mitochondria, Metabolism, and Redox Mechanisms in Psychiatric Disorders
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“Interestingly, several of these genes encode rate-limiting enzymes in essential metabolic pathways (159, 333).”
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“As a consequence, most aspects of animal metabolism are under the control of this molecular oscillator (Green et al., 2008).”
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“Clocks Regulate Fat Metabolism under DR Circadian clocks are critical regulators of metabolism (Green et al., 2008; Kohsaka et al., 2007; Panda et al., 2002; Ramsey et al., 2007; Xu et al., 2011) and maintain temporal organization that optimizes various cellular functions (Kovac et al.”
The Circadian Clock Interacts with Metabolic Physiology to Influence Reproductive Fitness
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“…clock in the central nervous system is sufficient to drive behavioral rhythms of rest:activity, clocks in peripheral tissues are required for the circadian control of many other processes, including metabolism (Allada and Chung, 2010; Glossop and Hardin, 2002; Green et al., 2008).”
Selective Inhibition of Casein Kinase 1ϵ Minimally Alters Circadian Clock Period
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“bolic disorders, may have a circadian origin (Barnard and Nolan, 2008; Green et al., 2008).”
Diurnal Regulation of MTP and Plasma Triglyceride by CLOCK Is Mediated by SHP
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“For example, Clock/Bmal1 enhance expression of Rev-erba and albumin D element-binding protein (DBP) that regulate bile acid and drug metabolisms (Green et al., 2008; Lowrey and Takahashi, 2004; Hussain and Pan, 2009).”
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“Because nutrient signals can provide a potent entraining cue for peripheral circadian oscillators (Green et al., 2008; Bass and Takahashi, 2010; Mohawk et al., 2012), we investigated whether scheduled food restriction (FR) could restore circadian temporal organization of peripheral oscillators in forebrainspecific Bma…”
Self-citationPostindustrial Metabolism: Fat Knowledge
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The REV-ERBs and RORs: Molecular Links Between Circadian Rhythms and Lipid Homeostasis
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Chronobiological aspects of nutrition, metabolic syndrome and obesity
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“The CS is composed of [54,55]:”
- Authors
- Green, C. B., Takahashi, J. S., & Bass, J.
- Affiliations
- University of Virginia (US)
- Northwestern University (US)
- Corresponding author
- Takahashi, Joseph S.
- Bass, Joseph
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2008-09
- Volume
- 134
- Issue
- 5
- Pages
- 728-742
- ISSN
- 0092-8674 (ISSN-L)
- PMC
- PMC3760165
- OpenAlex
- W2063946784
- Cited by
- 902
- References
- 145
- Citations by year
- 2026: 22 · 2025: 29 · 2024: 29 · 2023: 33 · 2022: 51 · 2021: 49 · 2020: 36 · 2019: 44 · 2018: 35 · 2017: 52 · 2016: 56 · 2015: 51 · 2014: 65 · 2013: 61 · 2012: 74
- FWCI
- 7.74
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Howard Hughes Medical Institute
- Amylin Pharmaceuticals
- National Institutes of Health (5p50mh074924-05)
- National Institute on Aging (P01AG011412)
- National Heart, Lung, and Blood Institute (R01HL075029)
- National Institute of Mental Health (P50 MH-074924, R01MH078024)
- National Institute of General Medical Sciences (R01GM076626)
- 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 › Physiology › Dietary Effects on Health
- Keywords
- circadian rhythm, metabolism, circadian regulation, metabolic homeostasis, circadian gene expression, central nervous system, peripheral tissues, cardiovascular disease, obesity, diabetes mellitus
- MeSH terms
- Animals, Biological Clocks, Circadian Rhythm, Feeding Behavior, Humans, Metabolic Networks and Pathways
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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