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Cited by 632Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

Human Leptin Levels Are Pulsatile and Inversely Related to Pituitary–Ardenal Function

Licinio, Julio, Mantzoros, Christos, Negrão, Anadré B., Cizza, Giovanni, Wong, Ma-Li, Bongiorno, Peter B., Chrousos, George P., Karp, Brian +3 more·1997·Nature Medicine
DOI 10.1038/nm0597-575
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Abstract

Leptin communicates nutritional status to regulatory centers in the brain. Because peripheral leptin influences the activity of the highly pulsatile adrenal and gonadal axes, we sought to determine whether leptin levels in the blood are pulsatile. We measured circulating leptin levels every 7 minutes for 24 hours, in six healthy men, and found that total circulating leptin levels exhibited a pattern indicative of pulsatile release, with 32.0 +/- 1.5 pulses every 24 hours and a pulse duration of 32.8 +/- 1.6 minutes. We also show an inverse relation between rapid fluctuations in plasma levels of leptin and those of adrenocorticotropic hormone (ACTH) and cortisol that could not be accounted for on the basis of glucocorticoid suppression of leptin. As leptin levels are pulsatile, we propose that a key function of the CNS is regulated by a peripheral pulsatile signal. In a separate pilot study we compared leptin pulsatility in 414 plasma samples collected every 7 minutes for 24 hours from one obese woman and one normal-weight woman. We found that high leptin levels in the obese subject were due solely to increased leptin pulse height; all concentration-independent pulsatility parameters were almost identical in the two women. Leptin pulsatility therefore can be preserved in the obese.

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Crossref · 10.1038/nm0597-575

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29 of 29 references verified0 citation errors · 0 not checkable

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  • A significant inverse relationship between fluctuations in leptin, ACTH, and cortisol has been demonstrated in humans, independent of glucocorticoid effects on leptin.

    “A significant inverse relationship between fluctuations in leptin, ACTH, and cortisol has been demonstrated in humans, independent of glucocorticoid effects on leptin (13)”

    From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [13]

  • The synchronous but inverse relationship of cortisol and leptin fluctuations reported previously does not appear to be causal but is probably due to a third factor.

    “Thus, the synchronous but inverse relationship of cortisol and leptin fluctuations reported previously (13) does not appear to be causal but is probably due to a third factor.”

    From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [13]

  • Prior studies suggest a likely average of around 30 leptin pulses per day, with a range between 20 and 40 being possible.

    “These studies give a likely average of around 30 pulses per day of leptin, with a range between 20 to 40 being a possibility.”

    From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [39]

  • The average number of leptin secretory events was found to be 32.0 ± 1.5 per day, within a range of 29 to 39 pulses.

    “The average number of leptin secretory events was found to be 32.0 ± 1.5 per day (39), within a range of 29 to 39 pulses among the subjects.”

    From Sparse System Identification of Leptin Dynamics in Women With Obesity (2022) · cites this paper as [39]

  • Leptin reflects fat stores: its levels increase after meals and during the night and are associated with decreased appetite.

    “Leptin reflects fat stores: its levels increase after meals and during the night and are associated with decreased appetite (Fig. 2).74”

    From Interacting epidemics? Sleep curtailment, insulin resistance, and obesity (2012) · cites this paper as [74]

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Authors
Licinio, J., Mantzoros, C., Negrão, A. B., Cizza, G., Wong, M.-L., Bongiorno, P. B., Chrousos, G. P., Karp, B., Allen, C., Flier, J. S., & Gold, P. W.
Affiliations
  • Beth Israel Deaconess Medical Center (US)
  • National Institutes of Health (US)
ORCID
Venue
Nature Medicine
Publisher
Springer Science and Business Media LLC
Published
1997-05
Volume
3
Issue
5
Pages
575-579
ISSN
  • 1078-8956 (ISSN-L)
  • 1546-170X
DOI
10.1038/nm0597-575
OpenAlex
W2007482590
Cited by
632
References
29
Citations by year
2026: 6 · 2025: 7 · 2024: 7 · 2023: 9 · 2022: 8 · 2021: 11 · 2020: 5 · 2019: 12 · 2018: 10 · 2017: 6 · 2016: 12 · 2015: 13 · 2014: 21 · 2013: 12 · 2012: 23
FWCI
19.97
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Medicine (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
leptin, pulsatile hormone secretion, ACTH, cortisol, hypothalamic-pituitary-adrenal axis, obesity
MeSH terms
Adrenocorticotropic Hormone, Adult, Algorithms, Corticotropin-Releasing Hormone, Cushing Syndrome, Female, Humans, Hydrocortisone, Hypothalamo-Hypophyseal System, Male, Menstruation, Obesity, Pilot Projects, Pituitary-Adrenal System, Proteins, Leptin

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