Increased hypothalamic content of preproneuropeptide Y messenger ribonucleic acid in genetically obese Zucker rats and its regulation by food deprivation.

Neuropeptide Y (NPY) is a potent orexigenic agent capable of producing hyperphagia and obesity. NPY-containing neurons project from the hypothalmic arcuate nucleus to the paraventricular nucleus, an area known to be sensitive to the orexigenic effects of NPY. In this study we investigated the possibility that preproNPY messenger RNA (mRNA) content may be altered in obese Zucker rats compared to that of their lean littermates. Total RNA was isolated from hypothalamic dissections from male and female, obese and lean Zucker rats. RNA was also isolated from dissections of: olfactory bulb, entorhinal cortex, hippocampus, and striatum of female obese and lean rats. PreproNPY mRNA content was determined by solution hybridization-RNase protection analysis. The results revealed a 2- to 3-fold increase in preproNPY mRNA levels in the hypothalamus of obese animals compared to lean. The increase was observed in both sexes and was specific to the hypothalamus. In situ hybridization localized this increase to the arcuate nucleus. An additional RNase protection study was pursued to investigate the effects of 72 h food deprivation on hypothalamic preproNPY mRNA levels in lean and obese animals. Lean animals displayed an approximate 2-fold increase in preproNPY mRNA content, whereas obese animals showed no significant increase after food deprivation. These data are consistent with the hypothesis that NPY projections within the hypothalamus are involved in regulating feeding behavior and weight gain, and that disturbed regulation of hypothalamic NPY expression may play a role in the etiology of obesity in the genetically obese Zucker rat.