Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans

Schwartz, Michael W.; Peskind, Elaine; Raskind, Murray; Boyko, Edward J.; Porte, Daniel

doi:10.1038/nm0596-589

Cited by 1,014Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans

Schwartz, Michael W., Peskind, Elaine, Raskind, Murray, Boyko, Edward J., Porte, Daniel·1996·Nature Medicine

DOI 10.1038/nm0596-589

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Abstract

The adipocyte hormone, leptin (OB protein), is proposed to be an "adiposity signal" that acts in the brain to lower food intake and adiposity. As plasma leptin levels are elevated in most overweight individuals, obesity may be associated with leptin resistance. To investigate the mechanisms underlying brain leptin uptake and to determine whether reduced uptake may contribute to leptin resistance, we measured immunoreactive leptin levels in plasma and cerebrospinal fluid (CSF) of 53 human subjects. Leptin concentrations in CSF were strongly correlated to the plasma level in a nonlinear manner (r = 0.92; p = 0.0001). Like levels in plasma, CSF leptin levels were correlated to body mass index (r = 0.43; p = 0.001), demonstrating that plasma leptin enters human cerebrospinal fluid in proportion to body adiposity. However, the efficiency of this uptake (measured as the CSF:plasma leptin ratio) was lower among those in the highest as compared with the lowest plasma leptin quintile (5.4-fold difference). We hypothesize that a saturable mechanism mediates CSF leptin transport, and that reduced efficiency of brain leptin delivery among obese individuals with high plasma leptin levels results in apparent leptin resistance.

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Leptin and insulin enter the CNS in proportion to their plasma levels.
“both enter the CNS in proportion to their plasma level (160)”
From Leptin and the Central Nervous System Control of Glucose Metabolism (2011) · cites this paper as [160]

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Authors: Schwartz, M. W., Peskind, E., Raskind, M., Boyko, E. J., & Porte, D.
Affiliations: University of Washington (US)
ORCID: Schwartz, Michael W.
Peskind, Elaine
Raskind, Murray
Boyko, Edward J.
Venue: Nature Medicine
Publisher: Springer Science and Business Media LLC
Published: 1996-05
Volume: 2
Issue: 5
Pages: 589-593
ISSN: 1078-8956 (ISSN-L)
1546-170X
DOI: 10.1038/nm0596-589
OpenAlex: W2027427622
Cited by: 1,014
References: 19
Citations by year: 2026: 6 · 2025: 25 · 2024: 16 · 2023: 11 · 2022: 11 · 2021: 31 · 2020: 19 · 2019: 28 · 2018: 25 · 2017: 35 · 2016: 26 · 2015: 27 · 2014: 39 · 2013: 31 · 2012: 28
FWCI: 21.07
Type: journal article
Language: en
Open access: closed
Licence: www.springer.com/tdm (tdm)
Locations: Nature Medicine (publishedVersion)
PubMed (publishedVersion)
Funders: National Institutes of Health (2r01dk012829-36)
National Institute on Aging (AG 05136, P50AG005136)
National Institute of Diabetes and Digestive and Kidney Diseases (DK 12829)
National Institute of Neurological Disorders and Stroke (NS-32273)
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, cerebrospinal fluid, plasma leptin, adiposity, obesity, leptin resistance, body mass index, CSF/plasma ratio, saturable transport, appetite regulation
MeSH terms: Adult, Aged, Biological Transport, Blood, Cerebrospinal Fluid, Female, Humans, Male, Obesity, Proteins, Regression Analysis, Body Mass Index, Leptin

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Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans

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