Cited by 1,175Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance

Caro, José F, Kolaczynski, Jerzy W, Nyce, Mark R, Ohannesian, Joanna P, Opentanova, Irina, Goldman, Warren H, Lynn, Richard B, Zhang, Pei-Li +2 more·1996·The Lancet

Abstract

Background A receptor for leptin has been cloned from the choroid plexus, the site of cerebrospinal-fluid (CSF) production and the location of the blood/cerebrospinal-fluid barrier. Thus, this receptor might serve as a transporter for leptin. We have studied leptin concentrations in serum and (CSF).Methods and findings We demonstrated by radioimmunoassay and western blot the presence of leptin in human CSF. We then measured leptin in CSF and serum in 31 individuals with a wide range of bodyweight. Mean serum leptin was 318% higher in 8 obese (40.2 [SE 8.6] ng/mL) than in 23 lean individuals (9.6 [1.5] ng/mL, p < 0.0005). However, the CSF leptin concentration in obese individuals (0.337 [0.04] ng/mL) was only 30% higher than in lean people (0.259 [0.26] ng/mL, p < 0.1). Consequently, the leptin CSF/serum ratio in lean individuals (0.047 [0.010]) was 4.3-fold higher than that in obese individuals (0.011 [0.002], p < 0.05). The relation between CSF leptin and serum leptin was best described by a logarithmic function (r = 0 x 52, p < 0.01).Interpretation Our data suggest that leptin enters the brain by a saturable transport system. The capacity of leptin transport is lower in obese individuals, and may provide a mechanism for leptin resistance.

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Crossref · 10.1016/s0140-6736(96)03173-x

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  • Obesity causes resistance to leptin signaling, likely related to a post-receptor defect.

    “However, obese subjects have higher cerebrospinal fluid (CSF) leptin levels compared to lean subjects102 suggesting that obesity also causes resistance to leptin signaling, likely related to a post-receptor defect103.”

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Authors
Caro, J. F., Kolaczynski, J. W., Nyce, M. R., Ohannesian, J. P., Opentanova, I., Goldman, W. H., Lynn, R. B., Zhang, P.-L., Sinha, M. K., & Considine, R. V.
Affiliations
Thomas Jefferson University (US)
Corresponding author
Caro, José F
Venue
The Lancet
Publisher
Elsevier BV
Published
1996-07
Volume
348
Issue
9021
Pages
159-161
ISSN
  • 0099-5355 (ISSN-L)
  • 0140-6736
OpenAlex
W2147788805
Cited by
1,175
References
18
Citations by year
2026: 10 · 2025: 11 · 2024: 21 · 2023: 8 · 2022: 16 · 2021: 24 · 2020: 29 · 2019: 19 · 2018: 34 · 2017: 34 · 2016: 37 · 2015: 43 · 2014: 45 · 2013: 30 · 2012: 38
FWCI
19.06
Type
journal article
Language
en
Open access
closed
Locations
  • The Lancet (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (5r01dk045592-05)
  • National Institute of Diabetes and Digestive and Kidney Diseases (R01 DK 45592, R29DK051140, R29 DK51140)
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, serum leptin, obesity, leptin resistance, choroid plexus, leptin receptor, blood-brain barrier, saturable transport
MeSH terms
Biological Transport, Blood-Brain Barrier, Carrier Proteins, Female, Humans, Male, Middle Aged, Obesity, Proteins, Radioimmunoassay, Receptors, Cell Surface, Blotting, Western, Body Mass Index, Receptors, Cytokine, Leptin, Receptors, Leptin

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