Nam S Y, Kratzsch J, Kim K W, Kim K R, Lim S K, Marcus C
Division of Endocrinology, Department of Internal Medicine, Yonsei University, College of Medicine, 135-170 Seoul, Korea.
J Clin Endocrinol Metab. 2001 Oct;86(10):4849-53. doi: 10.1210/jcem.86.10.7939.
Leptin and its principal mediators, NPY and alpha-MSH are postulated to play a pivotal role in energy balance. To determine the possibility of the disturbance 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 after 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 normal weight women (mean BMI, 20.4 kg/m(2)). The CSF to plasma leptin ratio in normal weight subjects was 2.3-fold higher than that in obese subjects. After weight loss in obese subjects, plasma leptin levels decreased by 40% and CSF levels decreased by 51%. There was a positive linear correlation between CSF and plasma leptin levels at baseline in obese subjects (r = 0.74, P < 0.05) and a positive logarithmic correlation in normal weight subjects (r = 0.89, P < 0.05) and in obese subjects after weight loss (r = 0.64, P < 0.05). The BMI was negatively correlated with the CSF to plasma leptin ratio (r = -0.86, P < 0.05) in all subjects. Neither the baseline plasma levels nor the baseline CSF levels of NPY were different between normal weight subjects and obese subjects. After weight loss, the CSF NPY level decreased significantly compared with baseline values in obese subjects. The alpha-MSH levels in plasma and CSF did not differ significantly from controls in obese subjects at baseline or after weight loss. Baseline CSF leptin level correlated with neither the baseline CSF NPY level nor the baseline CSF alpha-MSH level. In conclusion, this study demonstrated that the efficiency of brain leptin delivery is reduced in human obesity and central nervous system leptin uptake involves a combination of a saturable and an unsaturable mechanism. CSF NPY and alpha-MSH did not differ from controls in human obesity, and the CSF NPY level decreased significantly whereas alpha-MSH did not differ after weight loss in obese subjects compared with baseline. There was no significant 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 balance in human obesity.
瘦素及其主要介质神经肽Y（NPY）和α-促黑素（α-MSH）被认为在能量平衡中起关键作用。为了确定人类肥胖中神经肽紊乱的可能性及其在负能量平衡下的相应变化，我们评估了肥胖女性在体重减轻前后血浆和脑脊液（CSF）中瘦素、NPY和α-MSH的水平，并与正常对照女性进行比较。研究对象包括16名肥胖女性[平均体重指数（BMI）为35.6kg/m²]，她们在接受为期2周的极低热量饮食（800千卡/天）诱导体重减轻前后，以及14名正常体重女性（平均BMI为20.4kg/m²）。正常体重受试者的脑脊液与血浆瘦素比值比肥胖受试者高2.3倍。肥胖受试者体重减轻后，血浆瘦素水平下降40%，脑脊液水平下降51%。肥胖受试者基线时脑脊液和血浆瘦素水平呈正线性相关（r = 0.74，P < 0.05），正常体重受试者以及肥胖受试者体重减轻后呈正对数相关（r = 0.89，P < 0.05；r = 0.64，P < 0.05）。所有受试者的BMI与脑脊液与血浆瘦素比值呈负相关（r = -0.86，P < 0.05）。正常体重受试者和肥胖受试者的NPY基线血浆水平和基线脑脊液水平均无差异。体重减轻后，肥胖受试者的脑脊液NPY水平与基线值相比显著降低。肥胖受试者在基线或体重减轻后，血浆和脑脊液中的α-MSH水平与对照组相比无显著差异。基线脑脊液瘦素水平与基线脑脊液NPY水平和基线脑脊液α-MSH水平均无相关性。总之，本研究表明，人类肥胖中脑内瘦素传递效率降低，中枢神经系统瘦素摄取涉及饱和和不饱和机制的组合。人类肥胖中脑脊液NPY和α-MSH与对照组无差异，肥胖受试者体重减轻后，脑脊液NPY水平显著降低，而α-MSH与基线相比无差异。脑脊液瘦素与脑脊液NPY或α-MSH之间无显著相关性。这可能是人类肥胖中存在瘦素抵抗和/或人类肥胖中调节食欲和能量平衡涉及更复杂机制的结果。
