Cerebrospinal fluid and plasma concentrations of leptin, NPY, and alpha-MSH in obese women and their relationship to negative energy balance

Leptin and its principal mediators, NPY and alpha -MSH are postulated to pl ay a pivotal role in energy balance. To determine the possibility of the di sturbance in neuropeptides in human obesity and their consequent changes in response to negative energy balance, we evaluated plasma and cerebrospinal fluid (CSF) leptin, NPY, and alpha -MSH levels in obese women before and a fter weight loss in comparison with normal control women. Subjects included 16 obese women [mean body mass index (BMI), 35.6 kg/m(2)] before and after weight loss induced by a 2-wk very low caloric diet (800 kcal/d) and 14 no rmal weight women (mean BM, 20.4 kg/m(2)). The CSF to plasma leptin ratio i n normal weight subjects was 2.3-fold higher than that in obese subjects. A fter weight loss in obese subjects, plasma leptin levels decreased by 40% a nd CSF levels decreased by 51%. There was a positive linear correlation be. tween CSF and plasma leptin levels at baseline in obese subjects (r = 0.74 , P < 0.05) and a positive logarithmic correlation in normal weight subject s (r 0.89, P < 0.05) and in obese subjects after weight loss (r = 0.64, P < 0.05). The BAH was negatively correlated with the CSF to plasma leptin rat io (r = -0.86, P < 0.05) in all subjects. Neither the baseline plasma level s nor the baseline CSF levels of NPY were different between normal weight s ubjects and obese subjects. After weight loss, the CSF NPY level decreased significantly compared with baseline values in obese subjects. The alpha -M SH levels in plasma and CSF did not differ significantly from controls in o bese subjects at baseline or after weight loss. Baseline CSF leptin level c orrelated with neither the baseline CSF NPY level nor the baseline CSF alph a -MSH level. In conclusion, this study demonstrated that the efficiency of brain leptin delivery is reduced in human obesity and central nervous system leptin upta ke involves a combination of a saturable and an unsaturabIe mechanism. CSF NPY and alpha -MSH did not differ from controls in human obesity, and the C SF NPY level decreased significantly whereas alpha -MSH did not differ afte r weight loss in obese subjects compared with baseline. There was no signif icant correlation between CSF leptin and CSF NPY or alpha -MSH. This could be the result of leptin resistance present in human obesity and/or the more complex mechanisms involved in modulating appetite and regulating energy b alance in human obesity.