The aim of the present study was to evaluate the cerebrospinal fluid (CSF)/serum
leptin ratio during pharmacological
therapy for
obesity with centrally and peripherally acting drugs. Thirty-one obese women (mean age, 32.3 +/- 10 yr; body mass index, 38.2 +/- 5.2 kg/m(2); body fat, 43.3 +/- 5.4%) were studied before and 2 months after a weight loss program consisting of a balanced diet (1200 kcal/d) plus
drug therapy. The patients were randomly assigned into three study groups: group I,
fenproporex 25 mg/d (n = 10); group II,
sibutramine 10 mg/d (n = 10); and group III,
orlistat 120 mg tid (n = 11). Body fat, measured by dual-energy x-ray absorptiometry, and serum and CSF concentrations of
leptin were examined at baseline and 2 months after
therapy. At baseline, clinical and biochemical characteristics of the groups were similar. All of the women lost weight, approximately 7.0% of their initial
body weight, and the reduction was not different among the groups. Serum
leptin fell significantly after 2 months in all groups, and the decline was proportional to the reduction in body fat, because
leptin levels adjusted for body fat did not change
after treatment. CSF
leptin levels showed a significant decrease after 2 months in all groups, and this decline was higher on group III compared with group I (P = 0.006). After
therapy, the CSF/serum
leptin ratio did not change in group I (1.57 +/- 0.3 to 1.72 +/- 0.62%) and group II (1.78 +/- 1.01 to 1.69 +/- 1.27%), whereas it declined significantly in group III (1.65 +/- 0.43 to 1.09 +/- 0.47%; P < 0.01), corresponding to a decrease of 33.3 +/- 22.5% for the CSF/serum
leptin ratio. The percentage change in group III was significantly different from the positive variation on group I (11.9 +/- 42.1%; P = 0.006) and close to the statistical significance compared with the negative variation seen in group II (-7.6 +/- 27.8%; P = 0.06). Our results showed that the CSF/serum
leptin ratio decreased after
weight loss in obese women treated during 2 months with
orlistat, whereas this ratio did not change in this period of time in obese women treated with
fenproporex and
sibutramine.