Journal of Korean Endocrine Society 2001;16(2):199-209.
Published online April 1, 2001.
Effect of weight loss on cerebrospinal Fluid and Plasma Concentrations of NPY, alpha -MSH and leptin in Obese Women.
Su Youn Nam, Kyung Wook Kim, Jun Hee Lee, Soo Jee Lee, Kyung Rae Kim, Young Duck Song, Sung Kil Lim, Hyun Chul Lee, Kap Bum Huh
Division of Endocrinology, Department of Internal Medicine, Yonsei University, College of Medicine, Seoul, Korea.
Abstract
BACKGROUND
Although leptin and its principal mediators, neuropeptide Y (NPY) and -melanocyte stimulating hormone (MSH) are postulated to play a pivotal role in the energy balance in experimental animals, the physiologic roles of leptin and its molecular targets are not fully identified in cases of human obesity. METHODS: The subjects consisted of 16 obese women (mean BMI 35.6 kg/m2) before and after weight loss that was induced by a 2 week-very low caloric diet (800 kcal/day) and 14 normal weight women (who had a mean BMI of 20.4 kg/m2). We evaluated the plasma and cerebrospinal fluid (CSF) leptin, NPY and alpha -MSH levels and their relationship in normal weight and obese women. Additionally, changes of these peptides during a negative energy balance (800 kcal/day) were assessed in causes of human obesity. RESULTS: Obese subjects exhibited a 6.3-fold higher plasma leptin level (21.9+/-1.2 vs 3.5+/-0.4 ng/mL, p<0.05) and a 2.8-fold higher CSF leptin level (0.29+/-0.02 vs 0.10+/-0.01 ng/mL, p<0.05) compared to control subjects. The CSF/plasma leptin ratio in normal weight subjects was 2.3-fold higher than that in obese subjects. After a weight loss in obese subjects, the plasma leptin level decreased by 40% and the CSF level decreased by 51%. The CSF/plasma leptin ratio was slightly lower than the baseline level. There was a positive linear correlation between CSF and plasma leptin level at the baseline in obese subjects (r= 0.74, p<0.05) and a positive logarithmic correlation in normal weight subjects and in obese subjects after a weight loss (r= 0.66, p<0.05). The BMI negatively correlated with the CSF/plasma leptin ratio (r=-0.86, p<0.05) in any subjects. Neither the baseline plasma levels nor the baseline CSF levels of NPY were different between the normal weight subjects and obese subjects. After a weight loss the CSF NPY level decreased significantly compared to the baseline values in obese subjects. The alpha -MSH levels in plasma and CSF did not differ significantly from controls in obese subjects at the baseline or after a weight loss. The baseline CSF leptin level neither correlated with the baseline CSF NPY level nor the baseline CSF alpha -MSH level. CONCLUSION: These results demonstrated that the efficiency of leptin delivery to the CNS is reduced in human obesity and that the CNS leptin uptake involves the combination of saturable and unsaturable mechanisms. A marked reduction in the CSF leptin levels compared to the plasma level after a weight loss in obese subjects can be a potent stimulus for the body to regain weight. In contrast to the results that were observed in experimental animals, the CSF NPY and alpha -MSH did not differ from the controls in human obesity and there was no significant correlation between the CSF leptin and CSF of these neuropeptides. This could have resulted from leptin resistance in cases of human obesity although the mechanisms for this resistance remain to be determined.
Key Words: CSF, Leptin, NPY, alpha-MSH, Human, Obesity


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