Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect

doi:10.1016/0196-9781(92)90093-I

Peptides

Volume 13, Issue 3, May–June 1992, Pages 581-587

https://doi.org/10.1016/0196-9781(92)90093-I Get rights and content

Abstract

Neuropeptide Y (NPY) elicits eating when injected directly into the paraventricular nucleus (PVN) or perifornical hypothalamus (PFH). To identify the essential regions of the NPY molecule and the relative contributions of Y₁ and Y₂ receptors, the eating stimulatory potency of NPY was compared to that of its fragments, analogues, and agonists when injected into the PVN or PFH of satiated rats. Additionally, antisera to NPY was injected into the cerebral ventricles (ICV) to determine whether passive immunization suppresses the eating produced by mild food deprivation. Tests with NPY fragments revealed that NPY(2–36) was surprisingly potent, nearly three times more so than intact NPY. In contrast, fragments with further $N- terminal$ deletions were progressively less effective or ineffective, as was the free acid form of NPY. Collectively, this suggests that both $N$ - and $C- terminal$ regions of NPY participate in the stimulation of eating. Tests with agonists revealed that the putative Y₁ agonist [Pro³⁴]NPY elicited a strong dose-dependent feeding response, while the putative Y₂ agonist, C2-NPY, had only a small effect at the highest doses. Although this suggests mediation by Y₁ receptors, the uncharacteristically high potency of NPY(2–36) may additionally suggest that the receptor subtype underlying feeding is distinct from that mediating other responses. Additional results revealed that ICV injection of antisera to NPY, which should inactivate endogenous NPY, produced a concentration-dependent suppression of eating induced by mild food deprivation. This finding, along with published work demonstrating enhanced levels of hypothalamic NPY in food-deprived rats, suggests that endogenous NPY mediates the eating produced by deprivation.

References (49)

B. Beck et al.
Rapid and localized alterations of neuropeptide Y (NPY) in discrete hypothalamic nuclei with feeding status
Brain Res.
(1990)
R.S.L. Chang et al.
Specific [³H]propionyl-neuropeptide Y (NPY) binding in rabbit aortic membranes: Comparisons with binding in rat brain and biological responses in rat vas deferens
Biochem. Biophys. Res. Commun.
(1988)
J.T. Clark et al.
Neuropeptide Y (NPY)-induced feeding behavior in female rats: Comparison with human NPY ([Met17]NPY), NPY analog ([norLeu4]NPY) and peptide YY
Regul. Pept.
(1987)
H.M. Cox et al.
The effects of selective amino acid substitution upon neuropeptide Y antisecretory potency in rat jejunum mucosa
Peptides
(1991)
V. Donoso et al.
Neuropeptide Y (NPY), an endogenous presynaptic modulator of adrenergic neurotransmission in the rat vas deferens: Structural and functional studies
Peptides
(1988)
J.F. Flood et al.
Dissociation of the effects of neuropeptide Y on feeding and memory: Evidence for pre- and postsynaptic mediation
Peptides
(1989)
F.B. Jolicoeur et al.
In vivo structure activity study supports the existence of heterogeneous neuropeptide Y receptors
Brain Res. Bull.
(1991)
S.P. Kalra et al.
Structure-function analysis of stimulation of food intake by neuropeptide Y: Effects of receptor agonists
Physiol. Behav.
(1991)
S.F. Leibowitz et al.
Analysis of neuropeptide Y-induced feeding: Dissociation of Y₁ and Y₂ receptor effects on natural meal patterns
Peptides
(1991)
J.C. Martel et al.
Neuropeptide Y receptors in rat brain: Autoradiographic localization
Peptides
(1986)

I.S. McGregor et al.

Metabolic effects of neuropeptide Y injected into the sulcal prefrontal cortex

Brain Res. Bull.

(1990)

C.L. McLaughlin et al.

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

Physiol. Behav.

(1991)

J.E. Morley et al.

Peptide YY (PYY), a potent orexigenic agent

Brain Res.

(1985)

X. Paez et al.

Differential feeding responses evoked in the rat by NPY and NPY_1–27 injected intracerebroventricularly

Pharmacol. Biochem. Behav.

(1991)

F. Rioux et al.

The vasoconstrictor effect of neuropeptide Y and related peptides in the guinea pig isolated heart

Peptides

(1986)

A. Sahu et al.

Food deprivation and ingestion induce reciprocal changes in neuropeptide Y concentrations in the paraventricular nucleus

Peptides

(1988)

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.

Feeding and drinking elicited by central injection of neuropeptide Y: Evidence for a hypothalamic site(s) of action

Brain Res. Bull.

(1985)

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.

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

Life Sci.

(1984)

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)

B.D. White et al.

Adrenalectomy decreases neuropeptide Y mRNA levels in arcuate nucleus

Brain Res. Bull.

(1990)

J. Abens et al.

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

Cited by (270)

NPY and NPY receptors in the central control of feeding and interactions with CART and MC4R in Siberian sturgeon
2019, General and Comparative Endocrinology
Citation Excerpt :
NPY13-36 is a Y2 receptor agonist that gives it has a high affinity to NPY C-terminal fragments such as NPY3–36 and NPY13–36 (Zhang et al., 2014). In the present study, found that, food intake of Siberian sturgeon was significantly improved after injected injection of [Leu 31, Pro 34] NPY, this observation was similar to those observed in rat (Stanley et al., 1992) and goldfish (De Pedro et al., 2000). Interestingly, the injection of [Phe7, Pro34] pNPY (Y1 receptor agonist), in rats, inhibited the rat hypothalamus-pituitary–thyroid (HPT) axis and reduced thyrotropin-releasing hormone (TRH) expression in the paraventricular nucleus (PVN) (Fekete et al., 2002).
Neuropeptide Y (NPY) is the most powerful central neuropeptide implicated in feeding regulation via its receptors. Understanding the role of NPY system is critical to elucidate animal feeding regulation. Unlike mammal, the possible mechanisms of NPY system in the food intake of teleost fish are mostly unknown. Therefore, we investigated the regulatory mechanism of NPY and NPY receptors in Siberian sturgeon. In this study, we cloned the cDNA encoding NPY, and assessed the effects of different energy status on npy mRNAs abundance. The expression of npy was decreased in the brain after feeding 1 and 3 h. Besides, the expression of npy was increased after fasting within 15 days, while exhibiting significant decrease after refeeding. In order to further characterize the role of NPY receptor in fish, we performed acute intraperitoneal (i.p.) injection of NPY Y1 and Y2 receptor agonists, which is [Leu 31, Pro 34] NPY and NPY13-36 respectively. The results showed that the food intake of Siberian sturgeon was increased within 30 mins after injection of both Y1 and Y2 receptor agonist. To explore the relationship between NPY, NPY receptors and another appetite peptides, we examined the level of npy, cocaine- and amphetamine-regulated transcript (cart) and melanocortin-4 receptor (mc4r) by injected Y1 and Y2 receptor agonist. The results suggested that cart expression was regulated by NPY which acts on Y1 receptor or Y2 receptor. While mc4r expression just was mediated by NPY and Y1 receptor.
Mechanisms for AgRP neuron-mediated regulation of appetitive behaviors in rodents
2018, Physiology and Behavior
The obesity epidemic is a major health and economic burden facing both developed and developing countries worldwide. Interrogation of the central and peripheral mechanisms regulating ingestive behaviors have primarily focused on food intake, and in the process uncovered a detailed neuroanatomical framework controlling this behavior. However, these studies have largely ignored the behaviors that bring animals, including humans, in contact with food. It is therefore useful to dichotomize ingestive behaviors as appetitive (motivation to find and store food) and consummatory (consumption of food once found), and utilize an animal model that naturally displays these behaviors. Recent advances in genetics have facilitated the identification of several neuronal populations critical for regulating ingestive behaviors in mice, and novel functions of these neurons and neuropeptides in regulating appetitive behaviors in Siberian hamsters, a natural model of food foraging and food hoarding, have been identified. To this end, hypothalamic agouti-related protein/neuropeptide Y expressing neurons (AgRP neurons) have emerged as a critical regulator of ingestive behaviors. Recent studies by Dr. Timothy Bartness and others have identified several discrete mechanisms through which peripheral endocrine signals regulate AgRP neurons to control food foraging, food hoarding, and food intake. We review here recent advances in our understanding of the neuroendocrine control of ingestive behaviors in Siberian hamsters and other laboratory rodents, and identify novel mechanisms through which AgRP neurons mediate appetitive and consummatory behaviors.
Migraine: A disorder of metabolism?
2016, Medical Hypotheses
The treatment and prevention of migraine within the last decade has become largely pharmacological. While there is little doubt that the advent of drugs (e.g. triptans) has helped many migraine sufferers to lead a normal life, there is still little knowledge with respect to the factors responsible for precipitating a migraine attack. Evidence from biochemical and behavioural studies from a number of disciplines is integrated to put forward the proposal that migraine is part of a cascade of events, which together act to protect the organism when confronted by a metabolic challenge.
Degradation behavior of biocomposites based on cassava starch buried under indoor soil conditions
2014, Carbohydrate Polymers
Degradation of cassava (tapioca) starch based composite films during indoor soil burial experiments was analyzed using five factors, three levels Box–Behnken response surface design. From the results, it was observed that, increased water sorption promotes the entry of soil microorganism and it utilizes the starch films as a source of energy for their growth. The reduction in weight and mechanical property was associated with preferential loss of matrix components of the films. The microorganisms associated with the degradation of films were quantified and identified. Scanning electron microscopy (SEM) analysis showed the formation of patterns and cracks on the surface of the materials aged in the soils. From the results, second order polynomial models were developed for the responses. The results of the study demonstrated that, the tapioca starch based composites were showed a limited lifetime in biotic environment which make them suitable for being disposed in landfills after their use.
PYY<inf>(3-36)</inf> into the arcuate nucleus inhibits food deprivation-induced increases in food hoarding and intake
2013, Peptides
Citation Excerpt :
These results suggest a possible inhibitory role of PYY(3-36) in food hoarding. Antagonism of the Y2-R in the Arc using BIIE0246 causes short term increases in food intake by laboratory rats [1], effects similar to those of NPY Y1-R and Y5-R agonism [e.g., [24,45]]. NPY-Rs have a dual role in the control of food intake, where Y2-R and Y4-R agonism is anorexigenic and Y1-R and Y5-R agonism is orexigenic in other rodents [3,21,32].
Central administration of neuropeptide Y (NPY) increases food intake in laboratory rats and mice, as well as food foraging and hoarding in Siberian hamsters. The NPY-Y1 and Y5 receptors (Rs) within the hypothalamus appear sufficient to account for these increases in ingestive behaviors. Stimulation of NPY-Y2Rs in the Arcuate nucleus (Arc) has an anorexigenic effect as shown by central or peripheral administration of its natural ligand peptide YY (3-36) and pharmacological NPY-Y2R antagonism by BIIE0246 increases food intake. Both effects on food intake by NPY-Y2R agonism and antagonism are relatively short-lived lasting ∼4 h. The role of NPY-Y2Rs in appetitive ingestive behaviors (food foraging/hoarding) is untested, however. Therefore, Siberians hamsters, a natural food hoarder, were housed in a semi-natural burrow/foraging system that had (a) foraging requirement (10 revolutions/pellet), no free food (true foraging group), (b) no running wheel access, free food (general malaise control) or (c) running wheel access, free food (exercise control). We microinjected BIIE0246 (antagonist) and PYY_(3-36) (agonist) into the Arc to test the role of NPY-Y2Rs there on ingestive behaviors. Food foraging, hoarding, and intake were not affected by Arc BIIE0246 microinjection in fed hamsters 1, 2, 4, and 24 h post injection. Stimulation of NPY-Y2Rs by PYY_(3-36) inhibited food intake at 0–1 and 1–2 h and food hoarding at 1–2 h without causing general malaise or affecting foraging. Collectively, these results implicate a sufficiency, but not necessity, of the Arc NPY-Y2R in the inhibition of food intake and food hoarding by Siberian hamsters.
Effect of neuropeptide y on food intake in bullfrog larvae
2013, Peptides
Citation Excerpt :
NPY, NPY-related peptides and their receptor systems are involved in the control of many biological processes such as cardiovascular activity, sexual behavior, feeding, neuroendocrine activity and psychophysiological functions [2,36,48,50]. In particular, NPY has been considered the most potent orexigenic peptide acting via the NPY Y1 receptor-signaling pathway in the mammalian brain [13,16,22,26,49,53]. On the other hand, it has been demonstrated that the NPY Y2 and Y4 receptors play an important role in the regulation of psychomotor activity in mice [12,46,47,55].
Neuropeptide Y (NPY) is a potent orexigenic neuropeptide implicated in appetite regulation in mammals. However, except for teleost fish such as the goldfish and zebrafish, the involvement of NPY in the regulation of feeding in non-mammalian vertebrates has not been well studied. Anuran amphibian larvae feed and grow during the pre- and pro-metamorphic stages, but, thereafter they stop feeding as the metamorphic climax approaches. Therefore, orexigenic factors seem to play important roles in pre- and pro-metamorphic larvae. We investigated the role of NPY in food intake using bullfrog larvae including pre- and pro-metamorphic stages, and examined the effect of feeding status on the expression level of the NPY transcript in the hypothalamus. NPY mRNA levels in hypothalamus specimens obtained from larvae that had been fasted for 3 days were higher than those in larvae that had been fed normally. We then investigated the effect of intracerebroventricular (ICV) administration of NPY on food intake in the larvae. Cumulative food intake was significantly increased by ICV administration of NPY (5 and 10 pmol/g body weight, BW) during a 15-min observation period. The NPY-induced orexigenic action (10 pmol/g BW) was blocked by treatment with a NPY Y1 receptor antagonist, BIBP-3226 (100 pmol/g BW). These results indicate that NPY acts as an orexigenic factor in bullfrog larvae.

View all citing articles on Scopus

View full text

ArticleEvidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y1 receptor mediating this peptide's effect

Abstract

Brain Res.

Biochem. Biophys. Res. Commun.

Regul. Pept.

Peptides

Peptides

Peptides

Brain Res. Bull.

Physiol. Behav.

Peptides

Peptides

Brain Res. Bull.

Physiol. Behav.

Brain Res.

Pharmacol. Biochem. Behav.

Peptides

Peptides

Physiol. Behav.

Brain Res. Bull.

Peptides

Life Sci.

Brain Res.

Regul. Pept.

Brain Res. Bull.

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

Article
Evidence for neuropeptide Y mediation of eating produced by food deprivation and for a variant of the Y₁ receptor mediating this peptide's effect