RECIPROCAL REGIONAL CHANGES IN BRAIN NPY RECEPTOR DENSITY DURING DIETARY RESTRICTION AND DIETARY-INDUCED OBESITY IN THE RAT

Neuropeptide Y (NPY) potently induces feeding, reduces thermogenesis a nd induces obesity in rats when injected into the cerebral ventricles, Groups of male Wistar rats were either restricted to 60% of their nor mal daily food intake over 10 days or made obese by presenting them wi th a high-calorie diet rich in sugars and fat over 6 weeks. Food restr icted rats lost up to 20% of their body weight, compared with control rats and had large reductions in their body fat mass. By contrast, rat s with dietary-induced obesity weighed 26% more than controls due main ly to increased body fat mass, Quantitative receptor autoradiography d emonstrated reduced [I-125]PYY binding in the hypothalamic lateral (pe rifornical) and dorsal areas, hypothalamic ventromedial, arcuate and d orsomedial nuclei, hippocampal CA3 region, centromedial amygdaloid nuc leus and thalamic paraventricular and reuniens nuclei in dietary restr icted rats compared with controls. By contrast, regional [I-125]PYY bi nding was significantly increased in hypothalamic lateral and dorsal a reas, hypothalamic arcuate and dorsomedial nuclei, amygdaloid medial a nd centromedial nuclei, thalamic centromedial and paraventricular nucl ei of dietary obese rats versus controls. Masking NPY Y1 receptors wit h 1 mu M BIBP3226, a selective Y1 receptor antagonist, revealed that t he changes in [I-125]PYY binding in brains of food-restricted and diet ary-obese rats were due to changes in BIBP3226-insensitive binding sit es, presumably Y2 or Y5 NPY receptors. These data suggest that dietary -restriction stimulates NPY release resulting in down-regulation of NP Y Y5 'feeding' and/or Y2 receptors and reduced BAT thermogenesis there by providing an increased drive to eat to restore normal caloric intak e whilst reducing thermogenesis in order to conserve fat reserves. By contrast, the up-regulation of NPY Y5 and/or Y2 receptors in dietary-i nduced obesity is consistent with inhibition of NPY release in the hyp othalamus, amygdala and thalamus. Overall, we suggest that there is a regional increase in NPY release during negative energy balance, such as during food-restriction and a reduced regional release of NPY in po sitive energy balance, such as during hyperphagia associated with the development of obesity. (C) 1997 Elsevier Science B.V.