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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 (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]
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“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]
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“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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“cular disease, cancer, and metabolic disease [1–4].”
Circadian timing of metabolism in animal models and humans
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Reiter, R. J., Tan, D., Korkmaz, A., & Ma, S. (2011) · Annals of Medicine · doi:10.3109/07853890.2011.586365 · Cited by 249
“Within the last decade, the dependence of metabolism on the circadian system has been intensely investigated (15,46).”
Satoh, A., Brace, C. S., Ben-Josef, G., West, T., Wozniak, D. F., Holtzman, D. M., Herzog, E. D., & Imai, S.-I. (2010) · The Journal of Neuroscience · doi:10.1523/jneurosci.1385-10.2010 · Cited by 237
“SIRT1 was also expressed in the suprachiasmatic nucleus (SCN), a region important for the central regulation of circadian rhythm (Green et al., 2008) (Fig.”
Mammalian circadian clock and metabolism – the epigenetic link
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“Several observations support the idea that communication might be exerted by a combination of neuronal signals through the autonomic nervous system and humoral factors, of which glucocorticoids and retinoic acid are the most likely candidates (Antle and Silver, 2005; Green et al., 2008).”
SCFFBXL3 ubiquitin ligase targets cryptochromes at their cofactor pocket
Xing, W., Busino, L., Hinds, T. R., Marionni, S. T., Saifee, N. H., Bush, M. F., Pagano, M., & Zheng, N. (2013) · Nature · doi:10.1038/nature11964 · Cited by 234
“Two shorter versions of the protein, mCRY2 (1-527) and mCRY2 (1-512), were subsequently purified.”
InfluentialTemporal orchestration of circadian autophagy rhythm by C/EBPβ
Ma, D., Panda, S., & Lin, J. D. (2011) · The EMBO Journal · doi:10.1038/emboj.2011.322 · Cited by 234
“Temporal orchestration of circadian autophagy rhythm by C/EBPb”
Protecting the Melatonin Rhythm through Circadian Healthy Light Exposure
Bonmatí‐Carrión, M., Argüelles-Prieto, R., Martínez-Madrid, M. J., Reiter, R. J., Hardeland, R., Rol, M. A., & Madrid, J. A. (2014) · International Journal of Molecular Sciences · doi:10.3390/ijms151223448 · Cited by 254
“The circadian system (CS) consists of [11,12] (Figure 1): (a) Oscillatory machinery, including a central pacemaker, the SCN [13], and peripheral oscillators located in most tissues and cells [14].”
Cracking the O-GlcNAc code in metabolism
Ruan, H., Singh, J. P., Li, M., Wu, J., & Yang, X. (2013) · Trends in Endocrinology and Metabolism · doi:10.1016/j.tem.2013.02.002 · Cited by 224
“Many metabolic processes such as hormone secretion, nutrient uptake, gluconeogenesis, and oxidative phosphorylation have a daily cycle [77-79], driven by cellautonomous clock oscillators in the brain and metabolic tissues [80, 81].”
Clock is important for food and circadian regulation of macronutrient absorption in mice
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Chua, E. C.-P., Shui, G., Lee, I. T.-G., Lau, P., Tan, L.-C., Yeo, S.-C., Lam, B. D., Bulchand, S., Summers, S. A., Puvanendran, K., et al. (2013) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1222647110 · Cited by 221
“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).”
Lee, J., Moulik, M., Fang, Z., Saha, P., Zou, F., Xu, Y., Nelson, D. L., Ma, K., Moore, D. D., & Yechoor, V. K. (2013) · Molecular and Cellular Biology · doi:10.1128/mcb.01421-12 · Cited by 230
“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
Hastings, M. H., Maywood, E. S., & Brancaccio, M. (2019) · Biology · doi:10.3390/biology8010013 · Cited by 207
“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
Akashi, M., Soma, H., Yamamoto, T., Tsugitomi, A., Yamashita, S., Yamamoto, T., Nishida, E., Yasuda, A., Liao, J. K., & Node, K. (2010) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1003878107 · Cited by 196
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).”
Izumo, M., Pejchal, M., Schook, A. C., Lange, R. P., Walisser, J. A., Sato, T., Wang, X., Bradfield, C. A., & Takahashi, J. S. (2014) · eLife · doi:10.7554/elife.04617 · Cited by 184
“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
Garaulet, M., & Madrid, J. A. (2010) · Advanced Drug Delivery Reviews · doi:10.1016/j.addr.2010.05.005 · Cited by 177
“The CS is composed of [54,55]:”
Metadata
- 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 (medical) › 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
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