Pesonen U, Huupponen R, Rouru J, Koulu M
Department of Pharmacology, University of Turku, Finland.
Brain Res Mol Brain Res. 1992 Dec;16(3-4):255-60. doi: 10.1016/0169-328x(92)90233-2.
The Obese Zucker rat is a model of genetic obesity characterized by hyperphagia, hyperinsulinemia and other endocrine abnormalities. In order to elucidate pathogenetic mechanisms contributing to disturbed feeding behavior in these animals, the effect of food restriction on three hypothalamic neuropeptides involved in the control of food intake was studied. Eighteen male obese and 18 lean Zucker rats were randomly divided into two groups: half of the animals were food-restricted for 2 weeks, while the other half served as controls and were fed ad libitum. The levels of preproneuropeptide Y (preproNPY), preprocorticotropin releasing factor (preproCRF) and preprosomatostatin (preproSOM) mRNAs were determined using in situ hybridization technique. In addition, plasma insulin and corticosterone concentrations were analyzed. Food restriction significantly increased the expression of preproNPY mRNA in the arcuate nucleus in both Zucker phenotypes, while the expressions of preproCRF mRNA in the paraventricular nucleus (PVN) and preproSOM mRNA in the periventricular nucleus (PeV) were not altered. The expression of preproNPY mRNA was significantly greater in control obese animals compared to control lean animals. Food restriction lowered plasma insulin levels, but did not change plasma corticosterone levels. It is concluded that food restriction specifically activates NPY gene transcription in the arcuate nucleus the response being similar in both Zucker phenotypes. The results suggest that orexigenic NPY plays a role in the adaptation to altered feeding status.
肥胖型 Zucker 大鼠是一种遗传性肥胖模型，其特征为食欲亢进、高胰岛素血症及其他内分泌异常。为了阐明导致这些动物摄食行为紊乱的发病机制，研究了食物限制对三种参与食物摄入控制的下丘脑神经肽的影响。将 18 只雄性肥胖 Zucker 大鼠和 18 只瘦 Zucker 大鼠随机分为两组：一半动物进行 2 周的食物限制，另一半作为对照，自由进食。使用原位杂交技术测定前神经肽 Y（preproNPY）、前促肾上腺皮质激素释放因子（preproCRF）和前生长抑素（preproSOM）mRNA 的水平。此外，分析了血浆胰岛素和皮质酮浓度。食物限制显著增加了两种 Zucker 表型大鼠弓状核中 preproNPY mRNA 的表达，而室旁核（PVN）中 preproCRF mRNA 和室周核（PeV）中 preproSOM mRNA 的表达未改变。与对照瘦大鼠相比，对照肥胖动物中 preproNPY mRNA 的表达显著更高。食物限制降低了血浆胰岛素水平，但未改变血浆皮质酮水平。结论是食物限制特异性地激活了弓状核中的 NPY 基因转录，两种 Zucker 表型的反应相似。结果表明，促食欲的 NPY 在适应改变的摄食状态中起作用。
