HYPERPHAGIA IN OBESITY IS ASSOCIATED WITH A CENTRAL PEPTIDERGIC DYSREGULATION IN RATS
HYPERPHAGIA IN OBESITY IS ASSOCIATED WITH A CENTRAL PEPTIDERGIC DYSREGULATION IN RATS
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DOI：
10.1093/jn/120.7.806
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发表时间：
1990-07-01
影响因子：
4.2
通讯作者：
BURLET, C
中科院分区：
文献类型：
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作者：
BECK, B;BURLET, A;BURLET, C
食欲过盛和肥胖通常是相关的，导致这些综合征的生化修饰的起源可能是在下丘脑。事实上，食物摄入受到各种下丘脑核中的众多神经肽的调节，包括室旁核（PBN）、弓状核（ARC）、腹正中核（VMN）和视交叉上核（SCH）。在这些肽中，神经肽 Y (NPY) 是最有效的食物摄入诱导剂，而神经降压素 (NY) 则可减少食物摄入。我们在肥胖 Zucker 大鼠的下丘脑核显微解剖中测量了这两种肽，这些大鼠比瘦大鼠多吃 30% 的食物。神经肽Y和神经紧张水平呈相反方向变化：在食量过多的肥胖Zucker大鼠中，ARC（+30%）、PVN（+60%）和SCH（+94%）细胞核中的NPY浓度显着高于食量正常的大鼠，而ARC（-40%）、PVN（-31%）、VMN（-66%）和SCH中的NT水平显着较低(-47%) 细胞核。这两种变化都会增加食物摄入量。进食周期也可能会被修改，因为在视交叉上核中测量到两种肽的巨大变化，视交叉上核被认为是进食节律最重要的调节器。这些结果强化了这样的假设：肥胖症的增生与中枢神经系统的生化改变有关，因为肥胖大鼠中 NT 和 NPY 的外周状态没有改变。由于其他下丘脑肽（例如阿片肽和生长抑素）的水平也略有改变，因此可以得出结论，肥胖症中的食欲亢进与中枢肽能失调有关。对与这些肽受体发生特异性反应的药物的研究可能对治疗食欲亢进以及肥胖症产生有趣的影响。
Hyperphagia and obesity are often associated, and the origins of the biochemical modifications leading to these syndromes might be in the hypothalamus. Indeed, food intake is regulated by numerous neuropeptides in various hypothalamuc nuclei, including the paraventricular (PBN), arcuate (ARC), ventromedian (VMN) and suprachiasmatic (SCH) nuclei. Among these peptides, neuropeptide Y (NPY) is the most potent inducer of food intake whereas neurotensin (NY) decreases food intake. We measured these two peptides in microdissected hypothalamic nuclei in obese Zucker rats that ate 30% more food than their lean counterparts. Neuropeptide Y and neurotension levels varied in opposite directions: In the hyperphagic obese Zucker rats, the NPY concentrations were significantly greater than those in the lean normophagic rats in the ARC (+30%), PVN (+60%) and SCH (+94%) nuclei, wherea the NT levels were significantly lower in the ARC (-40%), PVN (-31%), VMN (-66%) and SCH (-47%) nuclei. Both these variations tend to increase food intake. Feeding periodicity might also be modified because large variations of the two peptides have been measured in the suprachiasmatic nucleus, which is considered the most important regulator of feeding rhythm. The results reinforce the hypothesis that hyperplagia in obesity is associated with a biochemical modification in the central nervous system because the peripheral status of NT and NPY was not modified in the obese rats. Because levels of other hypothalamic peptides, such as opioid peptides and somatostatin, are also slightly modified, it can be concluded that hyperphagia in obesity is associated with a central peptidergic dysregulation. Research on drugs reacting specifically with the receptor of these peptides might have interesting implications for the treatment of hyperphagia and, therefore, of obesity.