Department of Medicine, Division of Endocrinology and Metabolism, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. Department of Physiology and Biophysics, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. Department of Neurobiology and Behavior, State University of New York at Stony Brook, Stony Brook, New York 11794, USA. Department of Anatomy, Northeastern Ohio Universities College of Medicine, Rootstown, Ohio 44272, USA.
J Neuroendocrinol. 1992 Jun;4(3):353-7. doi: 10.1111/j.1365-2826.1992.tb00179.x.
The genetically obese Zucker rat is a well characterized model of early onset human obesity. Many of the endocrine and metabolic abnormalities of obese animals are common to other strains of genetically obese animals as well as morbidly obese humans. Neuropeptide Y (NPY), a potent orexigenic agent, was recently found to be elevated in adult obese animals compared to their lean littermates. In this study we first examined hypothalamic expression of preproNPY mRNA, using solution hybridization/ nuclease protection analysis, in phenotypically-matched, i.e. lean or obese, immature (5-week-old) and mature (33-week-old) animals. Although changes were not statistically different, a trend toward decreased hypothalamic preproNPY mRNA levels was detected in both lean and obese mature animals. We next compared hypothalamic preproNPY mRNA levels between age-matched lean and obese animals at 5, 14 and 33 weeks of age and found elevated preproNPY mRNA levels in obese rats at all three ages. These data suggest that increased levels of hypothalamic NPY are an early manifestation of the obese phenotype and may, therefore, contribute to hyperphagia and increased weight gain in obese Zucker rats.
遗传性肥胖 Zucker 大鼠是一种具有典型特征的人类早期肥胖症模型。肥胖动物的许多内分泌和代谢异常与其他遗传性肥胖动物以及病态肥胖人类的异常情况相同。神经肽 Y（NPY）是一种有效的食欲刺激剂，最近发现在成年肥胖动物中的含量高于其瘦型同窝仔。在这项研究中，我们首先使用溶液杂交/核酸酶保护分析，在表型匹配的即瘦型或肥胖型、不成熟（5 周龄）和成熟（33 周龄）动物中，检查下丘脑前蛋白 NPY mRNA 的表达。尽管变化没有统计学差异，但在瘦型和肥胖型成熟动物中均检测到下丘脑前蛋白 NPY mRNA 水平呈下降趋势。接下来，我们比较了 5、14 和 33 周龄时年龄匹配的瘦型和肥胖型动物的下丘脑前蛋白 NPY mRNA 水平，发现肥胖大鼠在所有三个年龄段的前蛋白 NPY mRNA 水平均升高。这些数据表明，下丘脑 NPY 水平升高是肥胖表型的早期表现，因此可能导致肥胖 Zucker 大鼠的过度进食和体重增加。
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