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The Cerebrospinal Fluid/Serum Leptin Ratio during Pharmacological Therapy for Obesity

SEMPR, Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná (A.M.R., R.B.R., H.D.L.S., C.L.B.), Curitiba, Brazil; Neurology Division (S.M.D.A.), Department of Internal Medicine, Hospital de Clinicas da Universidade Federal do Paraná, Curitiba, Brazil; and Laboratório Frischmann Aisengart (P.A.N.), Curitiba, Brazil

Address all correspondence and requests for reprints to: Cesar Luiz Boguszewski, M.D., Ph.D., Serviço de Endocrinologia e Metabologia do Hospital de Clínicas da Universidade Federal do Paraná, Rua Padre Camargo, 262, Curitiba, PR, Brazil, CEP: 80060-240. E-mail: . cesarlui{at}hc.ufpr.br

Abstract

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/m²; 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.

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