CEREBROSPINAL-FLUID LEPTIN LEVELS - RELATIONSHIP TO PLASMA-LEVELS ANDTO ADIPOSITY IN HUMANS

The adipocyte hormone, leptin (OB protein), is proposed to be an ''adi posity signal'' that acts in the brain to lower food intake and adipos ity(1-5). As plasma leptin levels are elevated in most overweight indi viduals, obesity may be associated with leptin resistance(6,7). To inv estigate the mechanisms underlying brain leptin uptake and to determin e whether reduced uptake may contribute to leptin resistance, we measu red immunoreactive leptin levels in plasma and cerebrospinal fluid (CS F) of 53 human subjects. Leptin concentrations in CSF were strongly co rrelated to the plasma level in a nonlinear manner (r = 0.92; P = 0.00 01). Like levels in plasma, CSF leptin levels were correlated to body mass index (r = 0.43; P = 0.001), demonstrating that plasma leptin ent ers human cerebrospinal fluid in proportion to body adiposity. However , the efficiency of this uptake (measured as the CSF:plasma leptin rat io) was lower among those in the highest as compared with the lowest p lasma leptin quintile (5.4-fold difference). We hypothesize that a sat urable mechanism mediates CSF leptin transport, and that reduced effic iency of brain leptin delivery among obese individuals with high plasm a leptin levels results in apparent leptin resistance.