Decreased cerebrospinal-fluid/serum leptin ratio in obesity: a possible mechanism for leptin resistance
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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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.”
From Obesity-Induced Hypertension: Interaction of Neurohumoral and Renal Mechanisms (2015) · cites this paper as [102]
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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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