Circulating leptin has saturable transport into intrathecal space in humans

Background Leptin is an adipocyte-derived hormone that is thought to provid e a negative feedback signal to control body fat mass by interacting with i ts hypothalamic receptor. The present study was undertaken to examine the u ptake of leptin in cerebrospinal fluid (CSF) space in humans and whether th e transport of leptin into CSF space is an active phenomenon or due to free access through the blood-CSF barrier. Methods We determined serum and CSF leptin concentrations by radioimmunoass ay in 17 men [42 +/- 4 years, mean +/- SE; body mass index (BMI) 27.3 +/- 1 .8 kg m(-2)] and 22 women (40 +/- 3 years, BMI 25.1 +/- 1.0 kg m(-2)). The function of the blood-CSF barrier was evaluated by determining the CSF/seru m albumin ratio. Results Serum leptin concentration was lower in male (5.8 +/- 1.6 mu g L-1) than in female subjects (13.1 +/- 1.7 mu g L-1, P = 0.001), whereas the co ncentrations of leptin in CSF were virtually identical in male (0.34 +/- 0. 03 mu g L-1) and female (0.36 +/- 0.03 mu g L-1) subjects. Serum leptin was correlated positively with BMI both in men (r = 0.89, P < 0.01, n = 10) an d in women (r=0.61, P<0.05, n=14), whereas no correlation between CSF lepti n concentration and BMI was found in either group. The CSF/serum leptin rat io correlated negatively with serum leptin concentration both in men (r=-0. 93, P<0.001) and in women (r = -0.77, P < 0.001) and with BMI both in men ( r = -0.75, P = 0.02, n = 10) and in women (r = -0.64, P < 0.02, n = 14). Th e CSF/serum albumin ratio was not correlated with the CSF/serum leptin rati o in either group. CSF leptin concentrations and the CSF/serum leptin ratio were Virtually identical in subjects with impaired and normal blood-CSF ba rrier function. Conclusion Thus, our data support the presence of a saturable and active tr ansporter of leptin from circulation into intrathecal space.