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

Lancet. 1996 Jul 20;348(9021):159-61. doi: 10.1016/s0140-6736(96)03173-x.


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.

Publication types

  • Comparative Study
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Biological Transport
  • Blood-Brain Barrier
  • Blotting, Western
  • Body Mass Index
  • Carrier Proteins / metabolism
  • Female
  • Humans
  • Leptin
  • Male
  • Middle Aged
  • Obesity / metabolism*
  • Proteins / metabolism*
  • Proteins / physiology
  • Radioimmunoassay
  • Receptors, Cell Surface*
  • Receptors, Cytokine / metabolism
  • Receptors, Leptin


  • Carrier Proteins
  • LEPR protein, human
  • Leptin
  • Proteins
  • Receptors, Cell Surface
  • Receptors, Cytokine
  • Receptors, Leptin