Observations on the Orexigenic Hypothalamic Neuropeptide Y‐System in Neonatally Overfed Weanling Rats
Observations on the Orexigenic Hypothalamic Neuropeptide Y‐System in Neonatally Overfed Weanling Rats
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DOI：
10.1046/j.1365-2826.1999.00357.x
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发表时间：
1999-07
影响因子：
3.2
通讯作者：
Plagemann;Harder;Rake;Waas;Melchior;Ziska;Rohde;Dörner
中科院分区：
文献类型：
--
作者：
Plagemann;Harder;Rake;Waas;Melchior;Ziska;Rohde;Dörner
产后早期营养过剩是青少年和成人肥胖的危险因素。潜在的病理生理机制仍不清楚。下丘脑神经肽决定性地参与体重和食物摄入的调节。在这项研究中，我们研究了与正常营养和营养不良相比，产后早期营养过剩对弓状核和室旁核 (PVN) 内 NPY 的影响。 Wistar 大鼠的正常产仔数在出生第三天从 10 只幼仔（正常窝数，NL；营养正常）调整为仅 3 只新生儿（小窝数，SL；营养过剩）或每只母亲 18 只幼仔（大窝数，LL；营养不良）。 SL大鼠直到出生后第21天出现明显超重（P<0.0001），以及高瘦素血症（P<0.001）和高胰岛素血症（P<0.01）。 LL 大鼠体重不足，瘦素和胰岛素浓度降低。使用放射免疫测定法，在下丘脑微孔中测定 NPY 含量，并在出生后第 21 天对连续下丘脑切片进行 NPY 免疫细胞化学分析。在体重不足、低瘦素血症和低胰岛素血症的 LL 大鼠中，观察到弓状核和 PVN 中 NPY 浓度增加，但在超重、高瘦素血症和高胰岛素血症的 SL 大鼠中，未发现 NPY 含量降低。此外，NPY 免疫阳性神经元占神经元总数的百分比不仅在 LL 大鼠中增加，而且在 SL 大鼠中也增加。由于 NPY 系统在这个年龄已经功能成熟，这些发现可能表明下丘脑 NPY 系统对出生后早期过度喂养的 SL 大鼠中胰岛素和/或瘦素水平升高产生了获得性抵抗。
Early postnatal overnutrition is a risk factor for obesity in juvenile and adult life. Underlying pathophysiological mechanisms are still unclear. Hypothalamic neuropeptides are decisively involved in the regulation of body weight and food intake. In this study, we investigated consequences of early postnatal overnutrition, as compared to normo‐and undernutrition, on NPY within the arcuate nucleus and paraventricular nucleus (PVN). The normal litter size of Wistar rats was adjusted on the third day of life from 10 pups (normal litters, NL; normonutrition) to only three newborns (small litters, SL; overnutrition) or 18 pups per mother (large litters, LL; undernutrition). SL rats developed clear overweight until the day 21 of life (P<0.0001), as well as hyperleptinaemia (P<0.001), and hyperinsulinaemia (P<0.01). LL rats were underweight and had decreased leptin and insulin concentrations. Using radioimmunoassay, NPY contents were determined in hypothalamic micropunches, and immunocytochemistry for NPY was performed in serial hypothalamic sections on day 21 of life. While in the underweight, hypoleptinaemic, and hypoinsulinaemic LL rats increased concentrations of NPY in the arcuate nucleus and PVN were observed, no decrease in NPY content was found in the overweight, hyperleptinaemic, and hyperinsulinaemic SL rats. Moreover, the percentage of NPY‐immunopositive neurones per total number of neurones was increased not only in the LL rats, but also in the SL rats. Since the NPY system is functionally mature already at this age, these findings might indicate an acquired resistance of the hypothalamic NPY system to increased levels of insulin and/or leptin in early postnatally overfed SL rats.