Rizk N M, Liu L S, Eckel J
Mansoura University, Department of Physiology, Egypt.
Int J Obes Relat Metab Disord. 1998 Dec;22(12):1172-7. doi: 10.1038/sj.ijo.0800742.
Increased levels of hypothalamic neuropeptide-Y (NPY) are thought to contribute to the manifestation of the obese phenotype. The aim of this study was to characterize the interactions between leptin, insulin and NPY in the pathogenesis of polygenic obesity.
A polygenic obese animal model, the New Zealand obese mouse (NZO) and its age-matched control, was used to assess the hypothalamic mRNA expression of NPY, the insulin receptor (IR) and the leptin receptor (Ob-Rb), by semiquantitative polymerase chain reaction. Experiments were performed early (at eight weeks old) and late (at 40 weeks old) in the life of these animals.
Serum glucose was significantly elevated in obese mice. Serum insulin levels were not different between obese and lean mice, whereas serum leptin levels were significantly elevated in obese mice and increased continuously during life [reaching extremely high values at 40 weeks (41.5+/-4.1 vs 3.4+/-0.25 ng/ml for obese and lean, respectively). The hypothalamic expression of NPY mRNA was significantly higher in NZO mice compared to controls at both eight weeks (2.3-fold) and 40 weeks (1.9-fold), respectively, whereas expression of IR and Ob-Rb remained unaffected.
Increased hypothalamic expression of NPY due to leptin resistance, may be involved in the development of polygenic obesity. Unchanged Ob-Rb expression suggests that either a defective hypothalamic uptake or defects in Ob-Rb signalling underly this process.
下丘脑神经肽Y（NPY）水平升高被认为与肥胖表型的表现有关。本研究的目的是确定瘦素、胰岛素和NPY在多基因肥胖发病机制中的相互作用。
使用多基因肥胖动物模型——新西兰肥胖小鼠（NZO）及其年龄匹配的对照，通过半定量聚合酶链反应评估下丘脑NPY、胰岛素受体（IR）和瘦素受体（Ob-Rb）的mRNA表达。在这些动物生命的早期（8周龄）和晚期（40周龄）进行实验。
肥胖小鼠的血清葡萄糖显著升高。肥胖小鼠和瘦小鼠的血清胰岛素水平无差异，而肥胖小鼠的血清瘦素水平显著升高，并在生命过程中持续增加[在40周时达到极高值（肥胖小鼠和瘦小鼠分别为41.5±4.1和3.4±0.25 ng/ml）]。与对照组相比，NZO小鼠在8周龄（2.3倍）和40周龄（1.9倍）时下丘脑NPY mRNA的表达均显著更高，而IR和Ob-Rb的表达未受影响。
由于瘦素抵抗导致下丘脑NPY表达增加，可能参与了多基因肥胖的发生发展。Ob-Rb表达未改变表明，下丘脑摄取缺陷或Ob-Rb信号传导缺陷是这一过程的基础。
