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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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Shimatani, H., Inoue, Y., Maekawa, Y., Miyake, T., Yamaguchi, Y., & Doi, M. (2021) · PLoS ONE · doi:10.1371/journal.pone.0252447 · Cited by 8
“Circadian clocks orchestrate multiple physiological rhythms in a synchronized manner [16, 17], but little is known about how these separate rhythms are regulated cumulatively.”
Basic Biology of Rhythms and the Microbiome
Heinemann, M., Ratiner, K., & Elinav, E. (2021) · Springer eBooks · doi:10.1007/978-3-030-72158-9_16 · Cited by 5
“The products of these genes can form the PER/CRY repressive complex that can translocate into the nucleus and inhibit CLOCK/BMAL1 transcription activity, subsequently resulting in PER and CRY gene repression (Green et al. 2008).”
How Light Resets Circadian Clocks
Johnsson, A., Helfrich‐Förster, C., & Engelmann, W. (2014) · Springer eBooks · doi:10.1007/978-1-4939-1468-5_18 · Cited by 5
Circadian Clocks: Evolution in the Shadows
Merrow, M. W., & Maas, M. F. P. M. (2009) · Current Biology · doi:10.1016/j.cub.2009.10.033 · Cited by 6
“transcription factors that form interlocked loops [1].”
Food anticipatory activity on a calorie-restricted diet is independent of Sirt1
Assali, D. R., Hsu, C. T., Gunapala, K. M., Aguayo, A., McBurney, M. W., & Steele, A. D. (2018) · PLoS ONE · doi:10.1371/journal.pone.0199586 · Cited by 6
Mármol‐Sánchez, E., Quintanilla, R., Cardoso, T. F., Jordana, J., & Amills, M. (2019) · Scientific Reports · doi:10.1038/s41598-019-45108-z · Cited by 6
Hamada, K., Oota, A., Ito, R., Kasahara, S., Nakajima, K., Kikuchi, Y., Sutherland, K. L., Ishikawa, M., Shirato, H., Ozaki, M., et al. (2020) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2020.05.224 · Cited by 6
Mota, M. C. (2017) · doi:10.14393/ufu.te.2018.486 · Cited by 6
Ganamurali, N., & Sabarathinam, S. (2025) · Chronobiology International · doi:10.1080/07420528.2025.2568586 · Cited by 5
“CRY proteins form repressor complexes with PER to inhibit CLOCK:BMAL1 activity, completing the negative feed-back loop (Green et al. 2008).”
Yuan, G.-C., Zhang, Q.-C., Ge, Y., Zeng, H.-J., Zhang, T., Ding, W., Dong, Z., Huang, Y.-K., Dong, J., Chen, N., et al. (2025) · Journal of Advanced Research · doi:10.1016/j.jare.2025.12.036 · Cited by 5
“The central nervous system interacts with surrounding tissues in a 24 h oscillation cycle to control nutrient metabolism, energy balance, redox state, and body behavior, and to maintain homeostasis through complex pathways [9].”
Wang, Y., Bo, Y., Lu, J., & Xu, Y. (2023) · Aquaculture Research · doi:10.1155/2023/3862965 · Cited by 5
“The system has great importance for their physiology, behavior, and metabolism [3 – 5], what is disrupted always produces a variety of physical problems, including metabolic disorders, behavioral impairments, etc. [6, 7].”
Onuma, S., & Kawai, M. (2024) · Endocrinology · doi:10.1210/endocr/bqae126 · Cited by 5
Changes in the Biorhythms of Biochemical Parameters in Animals with Modeled Acute Desynchronosis
Геннадьевна, Б. Е., Bakulev, S. E., Геннадьевна, Н. Т., Ivanov, M. B., Анатольевич, К. В., Zolotoverkhaja, E. A., Kostrova, T. A., & Sharabanov, A. V. (2020) · Bulletin of Experimental Biology and Medicine · doi:10.1007/s10517-020-05030-1 · Cited by 5
Chronic Treatment with Metformin Has No Disrupting Effect on the Hepatic Circadian Clock in Mice
Hasan, N., Sugimoto, K., Yamada, K., Morishige, J., Ushijima, K., Fujimura, A., Nagata, N., & Ando, H. (2022) · Medicina · doi:10.3390/medicina58020293 · Cited by 5
“Recently, accumulating evidence suggests that circadian regulation is closely linked to metabolic homeostasis [3,4], and therefore that impairment of circadian clocks contributes to the development of metabolic diseases, including obesity and type 2 diabetes.”
Wearable Cameras Reveal Large Intra-Individual Variability in Timing of Eating among Young Adults
Wang, L., Chan, V., Allman-Farinelli, M. A., Davies, A. J., Wellard‐Cole, L., & Rangan, A. (2022) · Nutrients · doi:10.3390/nu14204349 · Cited by 6
“These systems are involved in nutritionally-related metabolic processes such as glycolysis and gluconeogenesis, cholesterol and lipid metabolism, oxidative phosphorylation and detoxification [64,65].”
Huang, C., Yu, S., Yu, H.-S., Tu, H., Yeh, Y., & Yu, H. (2024) · Frontiers in Cellular and Infection Microbiology · doi:10.3389/fcimb.2023.1320713 · Cited by 5
“Circadian rhythm (CR) refers to an endogenous process that regulates the repeated timing of physiological function (Green et al., 2008; Asher and Schibler, 2011; Eckel-Mahan and Sassone-Corsi, 2013), and also ensures that one ’ s internal physiology is synchronized with external environment (Gachon…”
Dietary restriction modulates ultradian rhythms and autocorrelation properties in mice behavior
Kembro, J. M., Flesia, A. G., Acosta-Rodríguez, V. A., Takahashi, J. S., & Nieto, P. S. (2024) · Communications Biology · doi:10.1038/s42003-024-05991-3 · Cited by 6
Self-citationLiu, A. C., Shen, Y., Serbinski, C. R., He, H., Roman, D., Endale, M., Aschbacher‐Smith, L., King, K. A., Granadillo, J. L., López, I., et al. (2024) · Human Genetics and Genomics Advances · doi:10.1016/j.xhgg.2024.100333 · Cited by 9
“24 The circadian system in mammals consists of the central clock in the suprachiasmatic nuclei (SCN) of the hypothalamus and various cell and tissue clocks in the periphery.”
Resilience to Chronic Stress Is Characterized by Circadian Brain-Liver Coordination
Savva, C., Vlassakev, I., Bunney, B. G., Bunney, W. E., Massier, L., Seldin, M. M., Sassone‐Corsi, P., Petrus, P., & Sato, S. (2024) · Biological Psychiatry Global Open Science · doi:10.1016/j.bpsgos.2024.100385 · Cited by 5
“Thus, circadian disruption of neural rhythms could in fl uence peripheral metabolic oscillations and vice versa (8,14,15).”
The effect of l-carnosine on the circadian resetting of clock genes in the heart of rats
Wu, T., Tao, Y., Tsang, F., Abe, K., Xu, L., Jiang, Q., Xu, L., Fu, H., & Fu, Z. (2014) · Molecular Biology Reports · doi:10.1007/s11033-014-3745-x · Cited by 5
“tive effect on the circadian resynchronization of heart, which may be helpful for shift workers, as a lot of epidemiological reports have demonstrated that shift work is closely connected with a rising of cardiovascular disease and metabolic syndromes [25, 26].”
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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