Elsevier

Peptides

Volume 12, Issue 6, November–December 1991, Pages 1251-1260
Peptides

Analysis of neuropeptide Y-induced feeding: Dissociation of Y1 and Y2 receptor effects on natural meal patterns

https://doi.org/10.1016/0196-9781(91)90203-2Get rights and content

Abstract

To differentiate NPY receptor subtypes, Y1 and Y2, in terms of their impact on feeding behavior, the intact molecule NPY(1–36) and the 3 fragments, NPY(2–36), the Y1 agonist [Leu31,Pro34]NPY, and the Y2 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 Y1 agonist [Leu31,Pro34]NPY which, like NPY(1–36), also reduces protein intake. 4) The Y2 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 Y1 receptors mediate the stimulatory effect of NPY on carbohydrate intake and meal size, while Y2 receptors have the opposite effect of suppressing carbohydrate intake, possibly by altering presynaptic release of monoamines known to influence nutrient ingestion.

References (44)

  • C.L. McLaughlin et al.

    Full amino acid sequence of centrally administered NPY required for maximal food intake response

    Physiol. Behav.

    (1991)
  • P.J. Rogers et al.

    Meal patterns and food selection during the development of obesity in rats fed a cafeteria diet

    Neurosci. Biobehav. Rev.

    (1984)
  • S.P. Sheikh et al.

    Y1 and Y2 receptors for neuropeptide Y and related peptides

    FEBS Lett.

    (1989)
  • B.G. Stanley et al.

    Repeated hypothalamic stimulation with neuropeptide Y increases daily carbohydrate and fat intake and body weight gain in female rats

    Physiol. Behav.

    (1989)
  • B.G. Stanley et al.

    Paraventricular nucleus injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion

    Peptides

    (1985)
  • B.G. Stanley et al.

    Suppression of neuropeptide Y-elicited eating by adrenalectomy or hypophysectomy: Reversal with corticosterone

    Brain Res.

    (1989)
  • B.G. Stanley et al.

    Neuropeptide Y: Stimulation of feeding and drinking by injection into the paraventricular nucleus

    Life Sci.

    (1984)
  • D.L. Tempel et al.

    Diurnal variations in the feeding responses to norepinephrine, neuropeptide Y and galanin in the PVN

    Brain Res. Bull.

    (1990)
  • C. Wahlestedt et al.

    Neuropeptide Y (NPY) in the area of the hypothalamic paraventricular nucleus activates the pituitary adrenocortical axis in the rat

    Brain Res.

    (1987)
  • C. Wahlestedt et al.

    Evidence for different pre- and post-junctional receptors for neuropeptide Y and related peptides

    Regul. Pept.

    (1986)
  • H. Yokoo et al.

    The effect of neuropeptide Y (NPY) on stimulation-evoked release of [3H]norepinephrine (NE) from rat hypothalamic and cerebral cortical slices

    Eur. J. Pharmacol.

    (1987)
  • J. Abens et al.

    Synthetic fragments and analogs of NPY are ligands at NPY receptors in the rat cerebral cortex

  • Cited by (142)

    • Meal pattern alterations associated with intermittent fasting for weight loss are normalized after high-fat diet re-feeding

      2017, Physiology and Behavior
      Citation Excerpt :

      Not only is daily caloric intake dependent on meal size, but the number of meals and interaction between meal size and number are influenced by GI-derived peptides, such as cholecystokinin (CCK), amylin, and glucagon-like peptide-1 (GLP-1), and vagal-mediated signaling [32–34]. Previous studies from our laboratory have indicated that IMF for weight loss increases NPY in the hypothalamic arcuate nucleus (ARC) and norepinephrine (NE) in the medial hypothalamus [24], which could also influence meal patterns [35,36]. Therefore, understanding how dietary conditions, such as prolonged CR or IMF, alter meal patterns and microstructure can provide insight into the long-term effects of these types of dietary approaches.

    • Genetics of satiety

      2013, Satiation, Satiety and the Control of Food Intake
    • Peptide regulators of peripheral taste function

      2013, Seminars in Cell and Developmental Biology
    • Overexpression of neuropeptide Y in the dorsomedial hypothalamus increases trial initiation but does not significantly alter concentration-dependent licking to sucrose in a brief-access taste test

      2013, Physiology and Behavior
      Citation Excerpt :

      In contrast, prior behavioral training and stimulus exposure have been shown to interact with the effects of NPY so that, for example, ICV NPY administration can elicit increases in intraoral sucrose intake [6]. Furthermore, ICV NPY administration has been shown to increase the size of meal, which can be regarded as a measure of consummatory behavior with little or no significant change in meal frequency, which can be thought of as a measure of appetitive behavior [22,27]. Meal pattern analysis revealed that the decrease in chow intake observed in OLETF rats with knockdown of NPY expression in the DMH, was primarily attributed to a decrease in meal size compared to OLETF controls [42].

    View all citing articles on Scopus
    View full text