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Leptin Levels Are Dependent on Sleep Duration: Relationships with Sympathovagal Balance, Carbohydrate Regulation, Cortisol, and Thyrotropin
Open accessAbstract
Sleep plays an important role in energy homeostasis. The present study tests the hypothesis that circulating levels of leptin, a hormone that signals energy balance to the brain, are influenced by sleep duration. We also analyzed associations between leptin and sympathovagal balance, cortisol, TSH, glucose, and insulin under different bedtime conditions. Twenty-four-hour hormonal and glucose profiles were sampled at frequent intervals, and sympathovagal balance was estimated from heart rate variability in 11 subjects studied after 6 d of 4-h bedtimes (mean +/- sem of sleep duration during last 2 d: 3 h and 49 +/- 2 min) and after 6 d of 12-h bedtimes (sleep: 9 h and 03 +/- 15 min). A study with 8-h bedtimes was performed 1 yr later (sleep: 6 h and 52 +/- 10 min). Caloric intake and activity levels were carefully controlled in all studies. Mean levels, maximal levels, and rhythm amplitude of leptin were decreased (-19%, -26%, and -20%, respectively) during sleep restriction compared with sleep extension. The decrease in leptin levels was concomitant with an elevation of sympathovagal balance. The effects of sleep duration on leptin were quantitatively associated with alterations of the cortisol and TSH profiles and were accompanied by an elevation of postbreakfast homeostasis model assessment values. Measures of perceived stress were not increased during sleep restriction. During the study with 8-h bedtimes, hormonal and metabolic parameters were intermediate between those observed with 4-h and 12-h bedtimes. In conclusion, sleep modulates a major component of the neuroendocrine control of appetite.
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In the citing paper
“sleep loss, resulting from either acute total sleep deprivation or severe recurrent sleep restriction (≤5, 5 h/ night) resulted in elevated evening cortisol levels, often associated with a slower decline of cortisol concentrations across the day.[8][9][10][11][12][13][14][15][16][17]”
From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [10]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“These data implicate reduced leptin as a hormonal mechanism by which sleep restriction can worsen insulin sensitivity, increase circulating lipids, and lead to obesity and abdominal obesity via disruption of energy balance and increased cravings for carbohydrate rich foods.”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“This prompted the hypothesis that sleep restriction is linked with obesity via disruption of leptin and increased cravings for carbohydrate rich foods [17].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [17]
Experimental — accuracy not yet measuredThe source backs part of the claim, not all of it — or backs it for a different population, condition or comparison.
In the citing paper
“Both these pathways also have been proposed as possible mediators of the impairments in glucose tolerance associated with sleep restriction (22,44–48).”
From Sleep Restriction for 1 Week Reduces Insulin Sensitivity in Healthy Men (2010) · cites this paper as [47]
Experimental — accuracy not yet measuredThe cited source says what the claim attributes to it.
In the citing paper
“Severe sleep restriction results in elevated evening cortisol levels.”
From Effects of Insufficient Sleep on Pituitary–Adrenocortical Response to CRH Stimulation in Healthy Men (2017) · cites this paper as [10]
The cited source says what the claim attributes to it.
In the citing paper
“Some studies showed that sleep restriction significantly increases plasma cortisol levels during the late afternoon to early evening hours [17], [18], whereas others showed little to no changes [16], [21], [23], [27].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Early studies investigating the relationship between sleep restriction and leptin showed that sleep restriction decreased leptin levels [17], [19], and increased self-reported appetite and hunger [19].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“Early experimental studies exploring the relationship between sleep restriction and the adipose-derived hormone leptin found decreases after both two [19] and six [17] nights of sleep restriction to 4 h TIB.”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“several others have found elevated cortisol in the latter part of the day instead of the usual diurnal decline [17], [18], [54].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [17]
The cited source says what the claim attributes to it.
In the citing paper
“other published findings in the field which have previously documented decreases in leptin and increases in hunger and appetite following sleep restriction [17], [19].”
From Impact of Five Nights of Sleep Restriction on Glucose Metabolism, Leptin and Testosterone in Young Adult Men (2012) · cites this paper as [17]
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In the citing paper
“The approximate 30% reduction in cellular insulin signaling in adipocytes induced by 4 nights of sleep restriction lies within the range of the difference in insulin sensitivity in adipocytes from obese versus lean participants (30) and from diabetic patients versus nondiabetic participants (31).”
From Impaired Insulin Signaling in Human Adipocytes After Experimental Sleep Restriction: A Randomized, Crossover Study (2012) · cites this paper as [31]
Experimental — accuracy not yet measuredIn the citing paper
“Multiple studies have observed that sleep loss, either from acute partial or total sleep deprivation or from recurrent sleep curtailment or insomnia, results in elevated evening cortisol levels (12–19).”
From Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men (2014) · cites this paper as [15]
In the citing paper
“Consistent with our previous study of 6 nights of sleep restriction (15), we found that levels of perceived stress in the present study remained low and were not affected by sleep loss.”
From Adverse effects of two nights of sleep restriction on the hypothalamic-pituitary-adrenal axis in healthy men (2014) · cites this paper as [15]
In the citing paper
“Three studies assessed leptin at more than 2 time points in a rested sleep condition and in a sleep restriction condition in normal-weight men after similar food intake had been enforced in both conditions. All found decreased levels of anorexigenic leptin after sleep loss [62, 161, 162].”
From Sleep and metabolic function (2012) · cites this paper as [161]
In the citing paper
“In a study that assessed the 24-h leptin profiles after 6 days of 4-, 8-, and 12-h bedtimes in healthy lean young men under conditions of stable caloric intake and activity levels, all characteristics of the 24-h leptin profile (overall mean, nocturnal maximum, and amplitude) gradually increased from the 4- to the 12-h bedtime condition [161].”
From Sleep and metabolic function (2012) · cites this paper as [161]
In the citing paper
“Interestingly, cortisol evening levels observed under 8-hour bedtime condition were intermediate between those measured under 4-hour and 12-hour bedtime conditions [84] (Figure 5).”
From Impact of Sleep and Its Disturbances on Hypothalamo-Pituitary-Adrenal Axis Activity (2010) · cites this paper as [84]
In the citing paper
“short sleep duration (6 hours or less), and especially very short sleep duration (less than 5 hours) is associated with increased cardiometabolic morbidity and mortality, including weight gain and obesity, hypertension, hyperlipidemia, and diabetes.”
From Sleep: important considerations for the prevention of cardiovascular disease (2016) · cites this paper as [30]
In the citing paper
“insufficient sleep has been linked to lower energy expenditure, altered glucose homeostasis and alterations in hormones that mediate hunger(24, 25, 27-31).”
From Sleep: important considerations for the prevention of cardiovascular disease (2016) · cites this paper as [30]
In the citing paper
“SG was 30% lower in the state of sleep debt.”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [19]
In the citing paper
“AIRg was reduced by more than 30% after sleep restriction despite a trend for decreased SI.”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [19]
In the citing paper
“Glucose tolerance, assessed during an intravenous glucose tolerance test (ivGTT) and a high-carbohydrate breakfast, was lower in the sleep-debt condition than in the fully rested condition.”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [19]
In the citing paper
“For all these variables, clear changes are observed in a dose-response relationship with sleep duration.”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [19]
In the citing paper
“For instance, Panels D of Figure 2 show that all characteristics of the 24-h leptin profile (overall mean, nocturnal maximum, amplitude) gradually increased from the 4h to the 12h bedtime, signaling the brain an unnecessary need for extra caloric intake in a state of sleep debt.”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [19]
In the citing paper
“In a study that assessed the 24-h leptin profiles after 6 days of 4-h, 8-h, and 12-h bedtimes in healthy lean young men under conditions of stable caloric intake and activity levels, all characteristics of the 24-h leptin profile (overall mean, nocturnal maximum, amplitude) gradually increased from the 4-h to the 12-h bedtime condition [19] (Figure 2; panels D).”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [19]
In the citing paper
“HOMA levels post-breakfast increased from the 12-h to the 4-h in bed condition indicating a decrease in glucose tolerance and/or a decrease in SI proportional to the severity of sleep loss (Figure 2; panels A).”
From Role of sleep duration in the regulation of glucose metabolism and appetite (2010) · cites this paper as [19]
In the citing paper
“Following partial sleep deprivation, mean daytime values of leptin were approximately 18% lower compared to the rested state.104,105”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [105]
In the citing paper
“After two 4-h nights, there was a 24% increase in daytime appetite ratings;105 in addition, sleep deprivation specifically increased appetite for sweet and salty foods.”
From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [105]
In the citing paper
“Similarly, 4 hours in bed per night for 6 days significantly decreased leptin’s amplitude by 20% when compared with 12 hours in bed per night for 6 nights in 11 lean men [39].”
From Association between sleep deficiency and cardiometabolic disease: implications for health disparities (2016) · cites this paper as [39]
In the citing paper
“obstructive sleep apnea, which stimulates the SNS; 41,43,44”
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- Buxton OM, Spiegel K, Van Cauter E 2002 Chapter 8: Modulation of endocrine function and metabolism by sleep and sleep loss. In: Lee-Chiong TL, Sateia MJ, Carskadon MA, eds. Sleep Medicine. Handley, Philadelphia: Belfus, Inc.; 59 -69
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Sorted by citations
Obesity and Metabolic Syndrome in Circadian Clock Mutant Mice
Turek, F. W., Joshu, C., Kohsaka, A., Lin, E., Ivanova, G., McDearmon, E., Laposky, A., Losee-Olson, S., Easton, A., Jensen, D. R., et al. (2005) · Science · doi:10.1126/science.1108750 · Cited by 2,485
Adverse metabolic and cardiovascular consequences of circadian misalignment
Scheer, F. A. J. L., Hilton, M. F., Mantzoros, C. S., & Shea, S. A. (2009) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0808180106 · Cited by 2,351
Meta-Analysis of Short Sleep Duration and Obesity in Children and Adults
Cappuccio, F. P., Taggart, F. M., Kandala, N.-B., Currie, A., Peile, E., Stranges, S., & Miller, M. A. (2008) · Sleep · doi:10.1093/sleep/31.5.619 · Cited by 2,076
Pathophysiology of migraine: a disorder of sensory processing
Goadsby, P. J., Holland, P. R., Martins-Oliveira, M., Hoffmann, J., Schankin, C., & Akerman, S. (2017) · Physiological Reviews · doi:10.1152/physrev.00034.2015 · Cited by 1,998
Quantity and Quality of Sleep and Incidence of Type 2 Diabetes
Cappuccio, F. P., D'Elia, L., Strazzullo, P., & Miller, M. A. (2010) · Diabetes Care · doi:10.2337/dc09-1124 · Cited by 1,670
Metadata
- Authors
- Spiegel, K., Leproult, R., L’Hermite-Balériaux, M., Copinschi, G., Penev, P. D., & Van Cauter, E.
- Affiliations
- Université Libre de Bruxelles (BE)
- University of Chicago (US)
- Venue
- The Journal of Clinical Endocrinology & Metabolism
- Publisher
- The Endocrine Society
- Published
- 2004-11
- Volume
- 89
- Issue
- 11
- Pages
- 5762-5771
- ISSN
- 0021-972X (ISSN-L)
- 1945-7197
- OpenAlex
- W2115505164
- Cited by
- 1,006
- References
- 69
- Citations by year
- 2026: 18 · 2025: 29 · 2024: 28 · 2023: 52 · 2022: 48 · 2021: 40 · 2020: 50 · 2019: 30 · 2018: 42 · 2017: 41 · 2016: 57 · 2015: 57 · 2014: 61 · 2013: 78 · 2012: 74
- FWCI
- 9.76
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- The Journal of Clinical Endocrinology & Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion, other-oa)
- Dépôt institutionnel de l'Université libre de Bruxelles (Université Libre de Bruxelles) (submittedVersion)
- Funders
- University of Chicago
- National Institutes of Health
- National Institute on Aging (P01AG011412, AG-11412)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK 20595, DK-41814, R01DK041814)
- National Center for Research Resources (M01-RR 00055, M01RR000055)
- Topics
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Life Sciences › Neuroscience › Cognitive Neuroscience › Sleep and Wakefulness Research
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
- Keywords
- leptin, sleep duration, sleep restriction, sleep extension, sympathovagal balance, heart rate variability, cortisol, thyroid-stimulating hormone, glucose, insulin, HOMA, carbohydrate regulation, energy homeostasis, appetite regulation, neuroendocrine regulation, perceived stress
- MeSH terms
- Adult, Homeostasis, Humans, Hydrocortisone, Male, Sleep, Sympathetic Nervous System, Thyrotropin, Time Factors, Vagus Nerve, Leptin, Carbohydrate Metabolism
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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