Analysis of neuropeptide Y-induced feeding: Dissociation of Y 1 and Y 2 receptor effects on natural meal patterns

Abstract

To differentiate NPY receptor subtypes, Y 1 and Y 2, in terms of their impact on feeding behavior, the intact molecule NPY(1–36) and the 3 fragments, NPY(2–36), the Y 1 agonist [Leu 31,Pro 34]NPY, and the Y 2 agonist NPY(13–36), were injected (100 pmol/0.3 μl) into the hypothalamic paraventricular nucleus (PVN) of freely feeding rats. A computer-automated data acquisition system was employed in these experiments to permit a detailed analysis of feeding over the 12-h nocturnal cycle, in animals maintained on pure macronutrient diets. The results demonstrate that: 1) NPY(1–36) potentiates feeding behavior, primarily carbohydrate ingestion, by increasing the size and duration of the first meal after injection, rather than by affecting meal number or feeding rate, suggesting that NPY acts through mechanisms of satiety. The potentiation of carbohydrate intake occurs in association with a suppression of protein intake, which is strongest during the second meal after injection and which further increases the proportion of carbohydrate in the diet. No changes in fat ingestion are seen. 2) NPY(2–36), with the N-terminal tyrosine residue deleted, is equally potent to NPY(1–36) in potentiating carbohydrate intake and increasing meal size; however, it is less selective than NPY(1–36), producing an additional, smaller increase in consumption of protein. 3) The stimulatory effect of these peptides on carbohydrate intake and meal size is similarly observed, with somewhat reduced potency, after PVN injection of the selective Y 1 agonist [Leu 31,Pro 34]NPY which, like NPY(1–36), also reduces protein intake. 4) The Y 2 receptor agonist, NPY(13–36), causes a decrease in the ingestion of carbohydrate, a smaller decline in protein intake, and a reduction in meal size. It is proposed that hypothalamic Y 1 receptors mediate the stimulatory effect of NPY on carbohydrate intake and meal size, while Y 2 receptors have the opposite effect of suppressing carbohydrate intake, possibly by altering presynaptic release of monoamines known to influence nutrient ingestion.