Influence of weeks of circadian misalignment on leptin levels
Open accessAbstract
The neurobiology of circadian, wakefulness-sleep, and feeding systems interact to influence energy homeostasis. Sleep and circadian disruptions are reported to be associated with increased risk of diabetes and obesity, yet the roles of energy balance hormones in these associations are largely unknown. Therefore, in the current study we aimed to assess the influence of several weeks of circadian misalignment (sleep and wakefulness occurring at an inappropriate biological time) on the anorexigenic adipocyte hormone leptin. We utilized data from a previous study designed to assess physiological and cognitive consequences of changes in day length and light exposure as may occur during space fight, including exploration class space missions and exposure to the Martian Sol (day length). We hypothesized that circadian misalignment during an exploration class spaceflight simulation would reduce leptin levels. Following a three-week ~8 hours per night home sleep schedule, 14 healthy participants lived in the laboratory for more than one month. After baseline data collection, participants were scheduled to either 24.0 or 24.6 hours of wakefulness-sleep schedules for 25 days. Changes in the phase of the circadian melatonin rhythm, sleep, and leptin levels were assessed. Half of participants analyzed exhibited circadian misalignment with an average change in phase angle from baseline of ~4 hours and these participants showed reduced leptin levels, sleep latency, stage 2 and total sleep time (7.3 to 6.6 hours) and increased wakefulness after sleep onset (all P < 0.05). The control group remained synchronized and showed significant increases in sleep latency and leptin levels. Our findings indicate that weeks of circadian misalignment, such as that which occurs in circadian sleep disorders, alters leptin levels and therefore may have implications for appetite and energy balance.
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Sleep displacement and altered meal timing from shift work disturb hormonal balance, including leptin and ghrelin.
“Sleep displacement and altered meal timing due to shift work disturb hormonal balance—including key regulators of satiety and hunger, the hormones leptin and ghrelin, respectively [13].”
From Shift Work: Disrupted Circadian Rhythms and Sleep—Implications for Health and Well-being (2017) · cites this paper as [13]
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Circadian Rhythms in Anesthesia and Critical Care Medicine
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“Numerous cross-sectional and prospective clinical studies have demonstrated that shorter duration and poor-quality sleep predicts the development of obesity and type 2 diabetes, even after age, body mass index, and various other confounding variables are taken into account.(32,36-41) In one study, sleep restriction to…”
BackgroundInfluentialZhang, S., Wang, Y., Wang, Z., Wang, H., Xue, C., Li, Q., Guan, W., & Yuan, J. (2020) · Occupational and Environmental Medicine · doi:10.1136/oemed-2019-106220 · Cited by 57 · see citing works
McHill, A. W., Hull, J. T., & Klerman, E. B. (2022) · Nutrients · doi:10.3390/nu14091800 · Cited by 56 · see citing works
“We have previously reported that fasted leptin and ghrelin are not independently different during CSR across circadian phases [25], and others have shown leptin to be reduced [9,50,51] and ghrelin increased during acute circadian misalignment [52], though these findings may be sex-dependent [53].”
BackgroundPersonality, Chrono-nutrition and Cardiometabolic Health: A Narrative Review of the Evidence
Al-Abdi, T., Andreou, E. P., Papageorgiou, A., Heraclides, A., & Philippou, E. (2020) · Advances in Nutrition · doi:10.1093/advances/nmaa051 · Cited by 43 · see citing works
“Even a few weeks of circadian misalignment, caused by eating and sleeping >12 h out of the habitual time phase, resulted in altered leptin concentrations, increased glucose and insulin concentrations, and appetite and energy imbalance (38, 40).”
BackgroundThe regulation of circadian clock by tumor necrosis factor alpha
Ertosun, M. G., Koçak, G., & Özeş, O. N. (2019) · Cytokine & Growth Factor Reviews · doi:10.1016/j.cytogfr.2019.04.001 · Cited by 40 · see citing works
Circadian clock disruptions and the risk of cancer
Lahti, T. A., Merikanto, I., & Partonen, T. (2012) · Annals of Medicine · doi:10.3109/07853890.2012.727018 · Cited by 35 · see citing works
Associations of Weekday and Weekend Sleep with Children’s Reported Eating in the Absence of Hunger
LeMay‐Russell, S., Tanofsky‐Kraff, M., Schvey, N. A., Kelly, N. R., Shank, L. M., Mi, S. J., Jaramillo, M., Ramirez, S., Altman, D. R., Rubin, A., et al. (2019) · Nutrients · doi:10.3390/nu11071658 · Cited by 38 · see citing works
Metabolic signals in sleep regulation: recent insights
Basheer, R., & Shukla, C. (2016) · Nature and Science of Sleep · doi:10.2147/nss.s62365 · Cited by 39 · see citing works
“10 Another promising evidence has emerged from the epidemiological studies using genome-wide associations revealing close linkage between sleep/circadian and metabolism-related genes.”
Circadian Rhythm of Substrate Oxidation and Hormonal Regulators of Energy Balance
Rynders, C. A., Morton, S. J., Bessesen, D. H., Wright, K. P., & Broussard, J. L. (2020) · Obesity · doi:10.1002/oby.22816 · Cited by 37 · see citing works
“While available evidence has suggested a small circadian component to leptin, the hormone appears to be largely driven by sleep/wake and fasting/food intake (23,35,36).”
BackgroundSleep timing is associated with self-reported dietary patterns in 9- to 15-year-olds
Thellman, K. E., Dmitrieva, J., Miller, A. L., Harsh, J., & LeBourgeois, M. K. (2017) · Sleep Health · doi:10.1016/j.sleh.2017.05.005 · Cited by 36 · see citing works
Markwald, R. R., & Wright, K. P. (2012) · Springer eBooks · doi:10.1007/978-1-4614-3492-4_8 · Cited by 33 · see citing works
Pagano, E. S., Spinedi, E., & Gagliardino, J. J. (2016) · Neuroendocrinology · doi:10.1159/000453317 · Cited by 31 · see citing works
Molzof, H. E., Peterson, C. M., Thomas, S. J., Gloston, G. F., Johnson, R. L., & Gamble, K. L. (2022) · Frontiers in Endocrinology · doi:10.3389/fendo.2022.876752 · Cited by 32 · see citing works
“The few studies that have previously examined the acute effects of circadian misalignment and/or simulated shift work have reported decreases in 24-h mean leptin levels (5, 15, 36).”
BackgroundToktaş, N., Erman, K. A., & Mert, Z. (2018) · Journal of Education and Training Studies · doi:10.11114/jets.v6i3a.3159 · Cited by 28 · see citing works
“…are affected by short sleep duration, short sleep duration causes changes in hormones related to appetite and it especially increases hunger and appetite for foods with high carbohydrate and calories (Kanerva et al., 2012; Nguyen & Wright, 2009; Sato-Mito et al., 2011b; Scheer et al., 2009).”
Yoshizaki, T., Kawano, Y., Tada, Y., Hida, A., Midorikawa, T., Hasegawa, K., Mitani, T., Komatsu, T., & Togo, F. (2013) · Journal of Biological Rhythms · doi:10.1177/0748730413489957 · Cited by 28 · see citing works
Fiore, G., Scapaticci, S., Neri, C. R., Azaryah, H., Escudero-Marín, M., Pascuzzi, M. C., Mendola, A. L., Mameli, C., Chiarelli, F., Campoy, C., et al. (2023) · Nutrition Reviews · doi:10.1093/nutrit/nuad122 · Cited by 27 · see citing works
Circadian Rhythm Disruption as a Contributor to Racial Disparities in Prostate Cancer
Dasari, S. S., Archer, M., Mohamed, N., Tewari, A. K., Figueiro, M. G., & Kyprianou, N. (2022) · Cancers · doi:10.3390/cancers14205116 · Cited by 24 · see citing works
Shift work relationships with same- and subsequent-day empty calorie food and beverage consumption
Lin, T., Park, C., Kapella, M. C., Martyn-Nemeth, P. A., Tussing-Humphreys, L. M., Rospenda, K. M., & Zenk, S. N. (2020) · Scandinavian Journal of Work Environment & Health · doi:10.5271/sjweh.3903 · Cited by 21 · see citing works
“Disrupted circadian rhythm has been linked to desynchronized appetite hormones (eg, decreased leptin) (7), which may increase appetite and food consumption (8).”
BackgroundLiu, Y., Yu, C., Wang, K., Kwan, M., & Tse, L. A. (2023) · Environments · doi:10.3390/environments10030039 · Cited by 21 · see citing works
Barger, L. K., Wright, K. P., Burke, T. M., Chinoy, E. D., Ronda, J. M., Lockley, S. W., & Czeisler, C. A. (2014) · Acta Astronautica · doi:10.1016/j.actaastro.2013.07.002 · Cited by 19 · see citing works
Li, Z., Huang, Q., Gao, X., Chung, V. C., Zhang, P., Shen, D., Zhang, X., Zhong, W.-F., Liu, D., Chen, P., et al. (2021) · Frontiers in Cardiovascular Medicine · doi:10.3389/fcvm.2021.769130 · Cited by 20 · see citing works
“The circadian shift toward evening causes a longer-term circadian misalignment, which strengthens the association with arterial hypertension (44).”
BackgroundWalsh, N. P., KASHI, D. S., Edwards, J. P., Richmond, C., Oliver, S. J., Roberts, R., Izard, R. M., Jackson, S., & Greeves, J. P. (2022) · SLEEP · doi:10.1093/sleep/zsac222 · Cited by 17 · see citing works
Cheng, W., Chen, H., Tian, L., Ma, Z., & Cui, X. (2023) · Frontiers in Physiology · doi:10.3389/fphys.2023.1157270 · Cited by 18 · see citing works
Hao, X., Song, H., Su, X. Y., Li, J., Ye, Y., Wang, C., Xu, X. D., Pang, G., Liu, W., Li, Z., et al. (2025) · Annals of Medicine · doi:10.1080/07853890.2025.2464223 · Cited by 17 · see citing works
Subjective irregular sleep is associated with metabolic syndrome: A cross-sectional study
Ogura, Y., Koyama, T., Ozaki, E., Omichi, C., & Uehara, R. (2022) · Preventive Medicine Reports · doi:10.1016/j.pmedr.2022.101844 · Cited by 15 · see citing works
Yoshizaki, T., Midorikawa, T., Hasegawa, K., Mitani, T., Komatsu, T., & Togo, F. (2014) · PLoS ONE · doi:10.1371/journal.pone.0106643 · Cited by 13 · see citing works
An Introduction to Circadian Endocrine Physiology: Implications for Exercise and Sports Performance
Postolache, T. T., Gulati, A., Okusaga, O. O., & Stiller, J. W. (2020) · Contemporary Endocrinology · doi:10.1007/978-3-030-33376-8_20 · Cited by 12 · see citing works
Bouillon‐Minois, J., Outrey, J., Pereira, B., Adeyemi, O. J., Sapin, V., Bouvier, D., Thivel, D., de Saint-Vincent, S., Ugbolue, U. C., Baker, J. S., et al. (2022) · Nutrients · doi:10.3390/nu14235009 · Cited by 11 · see citing works
Park, J. H., Park, H., Bae, S., & Kang, J. (2023) · International Journal of Environmental Research and Public Health · doi:10.3390/ijerph20021489 · Cited by 8 · see citing works
“Sleep displacement and altered meal timing due to shift work disturb hormonal balance [41] and glucose metabolism [42], and a long-term consequence of altered glucose metabolism shift work is associated with an increased risk of type 2 diabetes [43].”
BackgroundPotes, Y., Díaz-Luis, A., Bermejo-Millo, J. C., Pérez-Martínez, Z., de Luxán-Delgado, B., Rubio-González, A., Menéndez-Valle, I., Gutiérrez-Rodríguez, J., Solano, J. J., Caballero, B., et al. (2023) · Antioxidants · doi:10.3390/antiox12111962 · Cited by 8 · see citing works
Role of circadian clock in female embryo implantation
Zhou, Y., He, X., Chen, Z., Gou, Y., Zhou, K., Huang, J., Chen, M., Hong, J., & Gao, L. (2025) · Frontiers in Cell and Developmental Biology · doi:10.3389/fcell.2025.1607491 · Cited by 7 · see citing works
“Sleep deprivation and circadian misalignment contribute to obesity pathogenesis, primarily through metabolic dysregulation characterized by elevated ghrelin concentrations and suppressed leptin levels, thereby promoting positive energy intake (Wright, 2009; Qian et al., 2019).”
Social jetlag, circadian disruption, and cardiometabolic disease risk
Malone, S. K., Mendoza, M. A., & Patterson, F. (2019) · Elsevier eBooks · doi:10.1016/b978-0-12-815373-4.00018-6 · Cited by 7 · see citing works
Marino, G. M., & Arble, D. M. (2023) · Frontiers in Endocrinology · doi:10.3389/fendo.2023.1182506 · Cited by 7 · see citing works
“Individuals experiencing experimentally-induced circadian misalignment similarly exhibited increased glucose levels as well as reduced leptin and sleep efficiency when meals and sleep time occurred ~12h out-of-phase with their endogenous clock (3, 15, 16).”
BackgroundCampbell, K. J., Jiang, P., Olker, C. J., Lin, X., Kim, S. Y., Lee, C., Song, E. J., Turek, F. W., & Vitaterna, M. H. (2024) · Frontiers in Neurology · doi:10.3389/fneur.2024.1430989 · Cited by 6 · see citing works
Yoshizaki, T., Komatsu, T., Tada, Y., & Togo, F. (2023) · Public Health Nutrition · doi:10.1017/s1368980023000794 · Cited by 5 · see citing works
“Given that the misalignment between the sleep–wake cycle and the circadian rhythm causes physical/mental problems(17,42,43), interventions for having breakfast in the RS breakfast-skippers may also be effective for preventing physical/mental problems via the improvement of the misalignment on the days of the DS.”
BackgroundNourishing the brain on deep space missions: nutritional psychiatry in promoting resilience
Pathare, N. N., Fayet‐Moore, F., Fogarty, J. A., Jacka, F. N., Strandwitz, P., Strangman, G. E., & Donoviel, D. B. (2023) · Frontiers in Neural Circuits · doi:10.3389/fncir.2023.1170395 · Cited by 7 · see citing works
ŞAHİN, T., & Tozcu, D. (2022) · International Journal of Science Letters · doi:10.38058/ijsl.1053393 · Cited by 4 · see citing works
Teng, N. I. M. F., Juliana, N., Nadhra, A., Dalila, A., Nursyafiqa, Nasuha, S. I., & Das, S. (2023) · Chronobiology International · doi:10.1080/07420528.2023.2267679 · Cited by 5 · see citing works
“Further, circadian disruption caused by irregular eating may cause abnormal leptin concentrations, elevated glucose and insulin concentrations, and disruptions in appetite and energy, which then contributed to weight gain (Nguyen and Wright 2010).”
BackgroundAktürk, B. E., Aslan, E., & Kaya, A. E. (2024) · European Journal of Therapeutics · doi:10.58600/eurjther2371 · Cited by 3 · see citing works
“Disruptions in the sleep-wake cycle can lead to metabolic dysfunctions such as a decrease in the appetite-regulating anorexigenic hormone “leptin,” resulting in overeating behaviour and ultimately obesity [12].”
An Introduction to Circadian Endocrine Physiology: Implications for Exercise and Sports Performance
Okusaga, O. O., & Postolache, T. T. (2013) · Humana Press eBooks · doi:10.1007/978-1-62703-314-5_20 · Cited by 3 · see citing works
Circadian Regulation of Sleep: From Genes to Circuits
Hameed, N. A., & Barber, A. F. (2024) · Springer eBooks · doi:10.1007/978-3-031-62723-1_14 · Cited by 2 · see citing works
The Impact of Shift Work-Related Circadian Rhythm Disruption on Inflammatory Biomarkers
Suyagh, M. F., Alefishat, E. A., Farha, R. K. A., Akour, A. A., Kasabri, V. N., & Bulatova, N. (2018) · Jordan Journal of Pharmaceutical Sciences · Cited by 2 · see citing works
Does sleep impact mobility in adults? A scoping reviewPreprint
Siengsukon, C. F., Beheshti, M., Donkers, S. J., Costa, S. L., Vaduvathiriyan, P., Glaser, A., Baber, G., & Williams, J. A. (2025) · medRxiv · doi:10.1101/2025.05.05.25326996 · Cited by 2 · see citing works
Better sleep is associated with improved mobility in adults: a scoping review
Siengsukon, C. F., Beheshti, M., Donkers, S. J., Costa, S. M. L. C., Vaduvathiriyan, P., Glaser, A., Baber, G., & Williams, J. (2026) · Journal of Rehabilitation Medicine · doi:10.2340/jrm.v58.44109 · Cited by 1 · see citing works
“Disruption of circadian rhythms has increasingly been identified as a significant factor contributing to impaired physiological processes and the development of various diseases, particularly metabolic dysregulation (24–26).”
Gubin, D. G., Kolomeichuk, S., Danilenko, K. V., Stefani, O., Markov, A. G., Petrov, I. M., Voronin, K., Mezhakova, M. S., Borisenkov, M. F., Shigabaeva, A., et al. (2026) · Chronobiology International · doi:10.1080/07420528.2026.2693222 · Cited by 1 · see citing works
“The broader literature supports the role of circadian rhythms in metabolic health: leptin exhibits its own rhythm and is influenced by sleep/wake and feeding (Shea et al. 2005) and circadian misalignment reduces leptin (Nguyen and Wright 2009).”
Associations between Serum 25-Hydroxyvitamin D Levels and Metabolic Syndrome in Male Shift Workers
Hee, S. S., Hee, K. N., Hyun, S. S., Hwan, L. Y., Young, M. J., Pyo, H. S., & Jin, C. S. (2023) · Annals of Endocrinology and Metabolism · doi:10.36959/433/571 · Cited by 1 · see citing works
McHill, A. W. (2014) · CU Scholar (University of Colorado Boulder) · Cited by 1 · see citing works
Sleep, exercise, and insulin sensitivity
Porter, J. W. (2020) · doi:10.32469/10355/78088 · Cited by 1 · see citing works
Impact of Circadian and Sleep Disruption on Metabolic Health and Behavior
Stothard, E. R. (2017) · CU Scholar (University of Colorado Boulder)
Medina, A. L. B. (2017) · Universidad San Ignacio de Loyola · doi:10.20511/usil.thesis/2906
Melatonin attenuates mitochondrial and metabolic dysfunction caused by leptin deficiencyPreprint
Potes, Y., Díaz-Luis, A., Bermejo-Millo, J. C., Pérez-Martínez, Z., de Luxán‐Delgado, B., Rubio‐González, A., Menéndez‐Valle, I., Gutiérrez‐Rodríguez, J., Solano, J. J., Caballero, B., et al. (2018) · bioRxiv (Cold Spring Harbor Laboratory) · doi:10.1101/466995
Overview and Understanding of Basic Circadian Physiology
Abbott, S. M., & Zee, P. C. (2019) · Springer eBooks · doi:10.1007/978-3-030-14738-9_3
Henst, R. H. P. (2020) · Open University of Cape Town (University of Cape Town)
Relationships between changes in sex hormones and serum leptin levels during the menstrual cycle
Avcı, B., & Bakan, N. (2021) · Black Sea Journal of Health Science · doi:10.19127/bshealthscience.871623
Circadian Rhythm and Health : Influence of Food Intake Timing and Regular Exercise
Lee, K., & Kim, S. K. (2023) · Korean Journal of Sport Science · doi:10.24985/kjss.2023.34.2.187
Kresna, A., Fuk, L. J., Widyahening, I. S., Soemarko, D. S., & Fitriani, D. Y. (2023) · Occupational and Environmental Medicine Journal of Indonesia · doi:10.7454/oemji.v1i2.1022
- Authors
- Wright
- Affiliations
- University of Colorado Boulder (US)
- Corresponding author
- Wright
- Venue
- Nature and Science of Sleep
- Publisher
- Informa UK Limited
- Published
- 2009-12
- Volume
- 2
- Pages
- 9
- ISSN
- 1179-1608 (ISSN-L)
- PMC
- PMC3603689
- OpenAlex
- W2151963394
- Cited by
- 74
- References
- 48
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 3 · 2023: 12 · 2022: 8 · 2021: 2 · 2020: 7 · 2019: 7 · 2018: 5 · 2017: 5 · 2016: 2 · 2015: 2 · 2014: 7 · 2013: 5 · 2012: 4
- FWCI
- 0.60
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Nature and Science of Sleep (publishedVersion, cc-by-nc)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Dove Medical Press (Taylor and Francis Group) (submittedVersion, cc-by-nc)
- Funders
- National Aeronautics and Space Administration (NCC958)
- Takeda Pharmaceuticals North America
- Deutsches Krebsforschungszentrum
- National Space Biomedical Research Institute (NCC 9‐58)
- National Institutes of Health (NCC9-58, RR‐02635)
- National Heart, Lung, and Blood Institute (R01HL073196)
- National Center for Research Resources (M01 RR 02635, RR 000051, M01RR000051, M01RR002635)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Social Sciences › Psychology › Experimental and Cognitive Psychology › Sleep and Work-Related Fatigue
- Keywords
- circadian misalignment, leptin, sleep timing, circadian rhythm, melatonin rhythm, sleep latency, sleep duration, wake after sleep onset, energy homeostasis, spaceflight simulation, day length, light exposure, appetite
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