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

Nature Medicine volume 2, pages 589–593 (1996)Cite this article

Abstract

The adipocyte hormone, leptin (OB protein), is proposed to be an “adiposity signal” that acts in the brain to lower food intake and adiposity1–5. As plasma leptin levels are elevated in most overweight individuals, obesity may be associated with leptin resistance6,7. 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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Affiliations

  1. Department of Medicine, Education and Clinical Center, University of Washington School of Medicine, Seattle, Washington, 98105, USA

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

  2. Departments of Psychiatry and Behavioral Sciences and Geriatric Research, Education and Clinical Center, University of Washington School of Medicine, Seattle, Washington, 98105, USA

    Elaine Peskind & Murray Raskind

  3. Veterans Affairs Puget Sound Health Care System, 1660 South Columbian Way, Seattle, Washington, 98108, USA

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

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  1. Michael W. Schwartz
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  2. Elaine Peskind
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  3. Murray Raskind
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  4. Edward J. Boyko
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  5. Daniel Porte Jr.
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Schwartz, M., Peskind, E., Raskind, M. et al. Cerebrospinal fluid leptin levels: Relationship to plasma levels and to adiposity in humans. Nat Med 2, 589–593 (1996). https://doi.org/10.1038/nm0596-589

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  • DOI: https://doi.org/10.1038/nm0596-589

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