Regulation of homeostasis by neuropeptide Y: involvement in food intake

2021 ◽  
Vol 28 ◽  
Author(s):  
Pilar Marcos Rabal ◽  
Rafael Coveñas
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Combination Therapies ◽  
Npy Receptor ◽  
Single Target ◽  
Orexigenic Peptide ◽  
Other Substances ◽  
Treatment Of Obesity ◽  
Obesity Drugs ◽  
Obesity Treatments

: Obesity leads to several metabolic disorders and, unfortunately, current pharmacological treatments for obesity are not very effective. In feeding mechanisms, the hypothalamus and some neuropeptides play an important role. Many data show that neuropeptide Y (NPY) is involved in these mechanisms. The aim of this review is to update the physiological actions mediated by the orexigenic peptide NPY, via its receptors, in the control of food intake and to review its involvement in food intake disorders. The relationships between NPY and other substances involved in food intake mechanisms, hypothalamic and extra-hypothalamic pathways involved in feeding and the potential pharmacological strategies to treat obesity will be discussed. Some research lines, focused on NPY, to be developed in the future are suggested. Neuropeptide systems are associated with redundancy and then therapies directed against a single target are generally ineffective. For this reason, other targets for the treatment of obesity are mentioned. It seems that combination therapies are the best option for successful anti-obesity treatments: new and more specific NPY receptor antagonists must be tested as anti-obesity drugs alone and in combination therapies.

scholarly journals Involvement of the Orexinergic System in Feeding

2021 ◽  
Vol 12 (1) ◽  
pp. 86
Author(s):  
Pilar Marcos ◽  
Rafael Coveñas
Keyword(s):  
Receptor Interaction ◽  
Combination Therapies ◽  
Receptor Antagonists ◽  
Differential Function ◽  
Unique Role ◽  
Beneficial Effects ◽  
Single Target ◽  
Other Substances ◽  
Treatment Of Obesity ◽  
Obesity Treatments

To know the processes involved in feeding, the dysregulation of hypothalamic neuropeptides promoting anorexigenic/orexigenic mechanisms must be investigated. Many neuropeptides are involved in this behavior and in overweight/obesity. Current pharmacological strategies for the treatment of obesity are unfortunately not very effective and, hence, new therapeutic strategies must be investigated and developed. Due to the crucial role played by orexins in feeding behavior, the aim of this review is to update the involvement of the orexinergic system in this behavior. The studies performed in experimental animal models and humans and the relationships between the orexinergic system and other substances are mentioned and discussed. Promising research lines on the orexinergic system are highlighted (signaling pathways, heterogeneity of the hypothalamic orexinergic neurons, receptor-receptor interaction, and sex differences). Each of the orexin 1 and 2 receptors plays a unique role in energy metabolism, exerting a differential function in obesity. Additional preclinical/clinical studies must be carried out to demonstrate the beneficial effects mediated by orexin receptor antagonists. Because therapies applied are in general ineffective when they are directed against a single target, the best option for successful anti-obesity treatments is the development of combination therapies as well as the development of new and more specific orexin receptor antagonists.

Food intake regulation in rodents: Y5 or Y1 NPY receptors or both?

2000 ◽  
Vol 78 (2) ◽  
pp. 173-185 ◽  
Author(s):  
Jacques Duhault ◽  
Michèle Boulanger ◽  
Susana Chamorro ◽  
Jean A Boutin ◽  
Odile Della Zuana ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Inhibitory Effect ◽  
Receptor Subtype ◽  
Pharmacological Characterization ◽  
Npy Receptor ◽  
Obesity Drugs ◽  
Npy Receptors

Neuropeptide Y (NPY), one of the most abundant peptides in rat and human brains, appears to act in the hypothalamus to stimulate feeding. It was first suggested that the NPY Y1 receptor (Y1R) was involved in feeding stimulated by NPY. More recently a novel NPY receptor subtype (Y5R) was identified in rat and human as the NPY feeding receptor subtype. There is, however, no absolute consensus since selective Y1R antagonists also antagonize NPY-induced hyperphagia. Nevertheless, new anti-obesity drugs may emerge from further pharmacological characterization of the NPY receptors and their antagonists. A large panel of Y1R and Y5R antagonists (such as CGP71683A, BIBO3304, BIBP3226, 1229U91, and SYNAPTIC and BANYU derivatives but also patentable in-house-synthesized compounds) have been evaluated through in vitro and in vivo tests in an attempt to establish a predictive relationship between the binding selectivity for human receptors, the potency in isolated organs assays, and the inhibitory effect on food intake in both normal and obese hyperphagic rodents. Although these results do not allow one to conclude on the implication of a single receptor subtype at the molecular level, this approach is crucial for the design of novel NPY receptor antagonists with potential use as anti-obesity drugs and for evaluation of their possible adverse peripheral side effects, such as hypotension.Key words: obesity, weight reduction, food intake, neuropeptide Y, rodents.

scholarly journals Central administration of Y5 receptor antisense decreases spontaneous food intake and attenuates feeding in response to exogenous neuropeptide Y

1998 ◽  
Vol 159 (2) ◽  
pp. 307-312 ◽  
Author(s):  
M Tang-Christensen ◽  
P Kristensen ◽  
CE Stidsen ◽  
CL Brand ◽  
PJ Larsen
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Receptor Subtypes ◽  
Central Administration ◽  
Feeding Response ◽  
Significant Weight Loss ◽  
Npy Receptor ◽  
Pre Treatment ◽  
Treatment Of Obesity ◽  
Stimulation Of

A number of neuropeptide Y (NPY) receptor subtypes, including the recently cloned Y5 receptor, have been implicated in the stimulation of food intake. In the present study, Y5 receptor antisense oligodeoxynucleotides (ODNs) were used to assess the potential involvement of the Y5 receptor in the regulation of spontaneous as well as NPY-induced food intake. Repeated central administration of Y5 antisense ODN significantly decreased spontaneous food intake and subsequently resulted in a significant weight loss. Furthermore, Y5 antisense ODN pre-treatment significantly inhibited the robust feeding response elicited by central administration of NPY (5.3+/-0. 8 vs 1.08+/-0.28 g, vehicle+/-s.e.m. vs Y5 ODN+/-s.e.m.). The present results provide evidence that central Y5 receptors are involved in both spontaneous as well as NPY-induced food intake, which may prove to be a new therapeutic route in the treatment of obesity and other disorders of appetite.

Neuropeptide Y inhibits estrous behavior and stimulates feeding via separate receptors in Syrian hamsters

2001 ◽  
Vol 280 (4) ◽  
pp. R1061-R1068 ◽  
Author(s):  
Eric S. Corp ◽  
Beatrice Gréco ◽  
J. Bradley Powers ◽  
Carrie L. Marín Bivens ◽  
George N. Wade
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Feeding Behavior ◽  
Sexual Behaviors ◽  
Peptide Yy ◽  
Receptor Subtypes ◽  
Syrian Hamsters ◽  
Total Food Intake ◽  
Npy Receptor ◽  
Estrous Behavior

Central injections of neuropeptide Y (NPY) increase food intake in Syrian hamsters; however, the effect of NPY on sexual behavior in hamsters is not known nor are the receptor subtypes involved in feeding and sexual behaviors. We demonstrate that NPY inhibits lordosis duration in a dose-related fashion after lateral ventricular injection in ovariectomized, steroid-primed Syrian hamsters. Under the same conditions, we compared the effect of two receptor-differentiating agonists derived from peptide YY (PYY), PYY-(3–36) and [Leu31,Pro34]PYY, on lordosis duration and food intake. PYY-(3–36) produced a 91% reduction in lordosis duration at 0.24 nmol. [Leu31,Pro34]PYY was less potent, producing a reduction in lordosis duration (66%) only at 2.4 nmol. These results suggest NPY effects on estrous behavior are principally mediated by Y2 receptors. PYY-(3–36) and [Leu31,Pro34]PYY stimulated comparable dose-related increases in total food intake (2 h), suggesting Y5 receptors are involved in feeding. The significance of different NPY receptor subtypes controlling estrous and feeding behavior is highlighted by results on expression of Fos immunoreactivity (Fos-IR) elicited by either PYY-(3–36) or [Leu31,Pro34]PYY at a dose of each that differentiated between the two behaviors. Some differences were seen in the distribution of Fos-IR produced by the two peptides. Overall, however, the patterns of expression were similar. Our behavioral and anatomic results suggest that NPY-containing pathways controlling estrous and feeding behavior innervate similar nuclei, with the divergence in pathways controlling the separate behaviors characterized by linkage to different NPY receptor subtypes.

scholarly journals A potent Neuropeptide Y (NPY) receptor antagonist 1229U91 suppresses spontaneous food intake in Zucker fatty rats

1997 ◽  
Vol 73 ◽  
pp. 180
Author(s):  
A. Ishihara ◽  
A. Kanatani ◽  
S. Asahi ◽  
T. Tanaka ◽  
M. Hidaka ◽  
...  
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Receptor Antagonist ◽  
Npy Receptor

NPY-leptin: opposing effects on appetitive and consummatory ingestive behavior and sexual behavior

2000 ◽  
Vol 278 (6) ◽  
pp. R1627-R1633 ◽  
Author(s):  
A. A. Ammar ◽  
F. Sederholm ◽  
T. R. Saito ◽  
A. J. W. Scheurink ◽  
A. E. Johnson ◽  
...  
Keyword(s):  
Sexual Behavior ◽  
Food Intake ◽  
Neuropeptide Y ◽  
Sucrose Solution ◽  
Ingestive Behavior ◽  
Female Rats ◽  
Male Rats ◽  
Intracerebroventricular Injection ◽  
Orexigenic Peptide ◽  
Opposing Effects

Many studies have indicated that neuropeptide Y (NPY) stimulates and leptin inhibits food intake. In line with this, intracerebroventricular injection of NPY (10 μg) stimulated and leptin (10 μg) inhibited intake of a sucrose solution when female rats were required to obtain the solution from a bottle. However, NPY inhibited and leptin stimulated intake if the solution was infused intraorally. Thus NPY stimulates the responses used to obtain food but inhibits those used to consume food, and leptin has the opposite effects. To test the specificity of these responses the sexual behavior of male rats was examined. NPY-treated males showed minor deficits in sexual behavior but chose to ingest a sucrose solution rather than copulate with a female if offered the choice. By contrast, leptin-treated males ingested little sucrose and displayed an increase in ejaculatory frequency if given the same choice. It is suggested that NPY is not merely an orexigenic peptide, but one that directs attention toward food. Similarly, leptin may not be an anorexic peptide, but one that diverts attention away from food toward alternate stimuli.

scholarly journals Ghrelin Interacts with Neuropeptide Y Y1 and Opioid Receptors to Increase Food Reward

Endocrinology ◽  
2012 ◽  
Vol 153 (3) ◽  
pp. 1194-1205 ◽  
Author(s):  
Karolina P. Skibicka ◽  
Rozita H. Shirazi ◽  
Caroline Hansson ◽  
Suzanne L. Dickson
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Opioid Receptor ◽  
Food Reward ◽  
Progressive Ratio ◽  
Receptor Expression ◽  
Food Motivation ◽  
Motivated Behavior ◽  
Orexigenic Peptide ◽  
Reward Motivation

Ghrelin, a stomach-derived hormone, is an orexigenic peptide that was recently shown to potently increase food reward behavior. The neurochemical circuitry that links ghrelin to the mesolimbic system and food reward behavior remains unclear. Here we examined the contribution of neuropeptide Y (NPY) and opioids to ghrelin's effects on food motivation and intake. Both systems have well-established links to the mesolimbic ventral tegmental area (VTA) and reward/motivation control. NPY mediates the effect of ghrelin on food intake via activation of NPY-Y1 receptor (NPY-Y1R); their connection with respect to motivated behavior is unexplored. The role of opioids in any aspect of ghrelin's action on food-oriented behaviors is unknown. Rats were trained in a progressive ratio sucrose-induced operant schedule to measure food reward/motivation behavior. Chow intake was measured immediately after the operant test. In separate experiments, we explored the suppressive effects of a selective NPY-Y1R antagonist or opioid receptor antagonist naltrexone, injected either intracerebroventricularly or intra-VTA, on ghrelin-induced food reward behavior. The ventricular ghrelin-induced increase in sucrose-motivated behavior and chow intake were completely blocked by intracerebroventricular pretreatment with either an NPY-Y1R antagonist or naltrexone. The intra-VTA ghrelin-induced sucrose-motivated behavior was blocked only by intra-VTA naltrexone. In contrast, the intra-VTA ghrelin-stimulated chow intake was attenuated only by intra-VTA NPY-Y1 blockade. Finally, ghrelin infusion was associated with an elevated VTA μ-opioid receptor expression. Thus, we identify central NPY and opioid signaling as the necessary mediators of food intake and reward effects of ghrelin and localize these interactions to the mesolimbic VTA.

scholarly journals The role of ghrelin in the regulation of food intake in patients with obesity and anorexia nervosa

2009 ◽  
pp. 159-170
Author(s):  
I Dostálová ◽  
M Haluzík
Keyword(s):  
Anorexia Nervosa ◽  
Food Intake ◽  
Current Knowledge ◽  
Gastrointestinal Hormones ◽  
Morbidly Obese ◽  
Potential Contribution ◽  
Weight Losses ◽  
Orexigenic Peptide ◽  
Treatment Of Obesity ◽  
Ghrelin Secretion

Gastrointestinal hormones play an important role in the neuroendocrine regulation of food intake and postprandial satiety. Ghrelin is a 28-amino acid orexigenic peptide produced mainly by the stomach that is involved in both the long-term regulation of body weight and the short-term regulation of postprandial satiety. Impairments in ghrelin secretion may in concert with other factors play an important role in the development of both obesity and anorexia nervosa. Despite an intensive research the critical factors regulating physiological postprandial ghrelin response in healthy individuals and its modification by the presence of obesity and anorexia nervosa are only partially understood. The potential contribution of ghrelin to the differences of diet- vs. surgical-induced weight losses in morbidly obese patients is now also being recognized. The aim of this review is to summarize the current knowledge about the physiology and pathophysiology of ghrelin and to discuss its potential in the prevention and/or treatment of obesity and anorexia nervosa.

Orexigenic effect of the melanocortin MC4 receptor antagonist HS014 is inhibited only partially by neuropeptide Y Y1 receptor selective antagonists

2000 ◽  
Vol 78 (2) ◽  
pp. 143-149 ◽  
Author(s):  
Ants Kask ◽  
Helgi B Schiöth ◽  
Jaanus Harro ◽  
Jarl ES Wikberg ◽  
Lembit Rägo
Keyword(s):  
Food Intake ◽  
Neuropeptide Y ◽  
Receptor Antagonist ◽  
Male Rats ◽  
Receptor Antagonists ◽  
Y1 Receptor ◽  
Npy Receptor ◽  
Inhibit Food Intake ◽  
In Vitro Data

Neuropeptide Y (NPY) and melanocortin (MC) peptides have opposite effects on food intake: NPY-like peptides and MC receptor antagonists stimulate feeding and increase body weight, whereas melanocortins and NPY antagonists inhibit food intake. In this study we tested whether the orexigenic effect of the selective MC4 receptor antagonist HS014 (1 nmol) could be inhibited by three different NPY antagonists, (R)-N2-(diphenylacetyl)-N-[(4-hydroxy-phenyl)methyl]- D-argininamide (BIBP3226), (R)-N-[[4-(aminocarbonylaminomethyl)-phenyl]methyl]-N2-(diphenylacetyl)-argininamide-trifluoroacetate (BIBO3304), and decapeptide [D-Tyr27,36D-Thr32]NPY27-36, after icv administration in freely feeding male rats. All three NPY receptor antagonists inhibited the orexigenic effects of HS014 partially and with markedly different potency. [D-Tyr27,36D-Thr32]NPY27-36 was active only in subconvulsive dose. The NPY Y1 selective antagonist BIBP3226 was more effective in inhibiting the effect of HS014 than BIBO3304 despite in vitro data indicating that BIBP3226 is about 10 times less potent than BIBO3304 at NPY Y1 receptor. An enantiomer of BIBO3304, BIBO3457, failed to inhibit HS014-induced feeding, indicating that the effects of BIBO3304 were stereoselective. These results suggest that stimulation of food intake caused by weakening of melanocortinergic tone at the MC4 receptor is partially but not exclusively related to NPY Y1 receptor activation.Key words: neuropeptide Y, NPY Y1 receptor antagonist, BIBO3304, BIBP3226, [D-Tyr27,36D-Thr32]NPY(27-36), 1229U91, food intake, MC4 receptor antagonist, HS014.

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