Structure-function analysis of stimulation of food intake by neuropeptide Y: Effects of receptor agonists

Kalra, Satya P.; Dube, Michael G.; Fournier, Alain; Kalra, Pushpa S.

doi:10.1016/0031-9384(91)90490-f

Cited by 132 publications

(51 citation statements)

References 23 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Several studies revealed that the Y1R subtype plays a prominent role in mediating feeding induced by NPY (22,23,47). Because gastric relaxation was also achieved by the Y1R in the present study, this gastric relaxation might be closely associated with food intake.…”

Section: Discussionsupporting

confidence: 64%

“…Kalra et al (24), citing a large number of studies, described NPY as the only messenger molecule for a physiological appetite transducer in the brain. Several studies revealed that the Y1 receptor subtype (Y1R) is the most prominent factor in mediating feeding induced by NPY (22,23,47). Feeding responses induced by melanin-concentrating hormone was attenuated by the antagonistic effects of Y1R (5).…”

mentioning

confidence: 99%

See 1 more Smart Citation

Central neuropeptide Y induces proximal stomach relaxation via Y1 receptors in the dorsal vagal complex of the rat

Kobashi¹,

Shimatani²,

Shirota³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

feeding; vagus; fundus; gastric; medulla NEUROPEPTIDE Y (NPY) is a peptide of 36 amino acids isolated from porcine brain (46). Potent appetite-stimulating effects of NPY are well known (8, 9). NPYergic transmissions are considered to be an essential component of the common final pathway in the hypothalamic integration of energy homeostasis. Kalra et al. (24), citing a large number of studies, described NPY as the only messenger molecule for a physiological appetite transducer in the brain. Several studies revealed that the Y1 receptor subtype (Y1R) is the most prominent factor in mediating feeding induced by NPY (22,23,47). Feeding responses induced by melanin-concentrating hormone was attenuated by the antagonistic effects of Y1R (5). Neurons containing other appetite-stimulating peptides, such as orexin or ghrelin, send information to NPY-containing neurons (12), and NPY is a key peptide in the regulation of body energy homeostasis.Besides the role of NPY in feeding behavior, NPY is involved in several abdominal functions. Centrally administered NPY regulated gastric acid secretion (14,17,34,38) and stimulated bile secretion via the Y1R (48). Microinjection of NPY into the dorsal vagal complex (DVC) enhanced basal motility of the antrum via Y1Rs (7). Centrally administered NPY delayed gastric emptying via Y2 receptors (Y2R) (18) and inhibited gastric distension-induced pyloric relaxation via Y1Rs (19). Thus NPY contributes to the control of digestion via upper abdominal functions. Gastric contractile activities that occur in the distal stomach are particularly important for digestion. In addition, accommodation of food is important for a smooth digestion. Tack et al. (45) described impaired accommodation related to functional dyspepsia symptoms. Gastric relaxation in the proximal stomach to accommodate ingested food is achieved by the intramural nervous system and extrinsic nervous system. Receptive relaxation is a well-known response achieved by the extrinsic nervous system (4), which arises from neurons in the dorsal motor nucleus of the vagus (DMV) (42). Thus the hindbrain is involved in the control of gastric motor activities. However, the relationship between NPY and gastric relaxation of the proximal stomach, which serves as a reservoir, has never been clarified. Recently, we suggested that administration of orexin-A, which is one of the appetite-stimulating peptides produced in the hypothalamus, into the fourth ventricle induced relaxation of the proximal stomach as well as an enhancement of distal stomach contractility (26). Because NPY affects DVC neurons that receive afferent information from the stomach (44) and send efferent information through axons to the gastrointestinal tract (3), it is possible that NPY induces gastric relaxation to accommodate ingested food.The present study was undertaken to demonstrate the role of NPY in gastric relaxation of the proximal stomach to accommodate food intake. The contribution of Y1Rs in the dorsal medulla to the relaxation of the proximal stomach induced by N...

show abstract

Section: Discussionsupporting

confidence: 64%

mentioning

confidence: 99%

Central neuropeptide Y induces proximal stomach relaxation via Y1 receptors in the dorsal vagal complex of the rat

Kobashi¹,

Shimatani²,

Shirota³

et al. 2006

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

show abstract

“…Injection of NPY or NPY-related peptides intracranially (either into the hypothalamus or cerebral ventricles) stimulates robust feeding (1)(2)(3)(4)(5)(6); conditions of energy deprivation (starvation) or increased energy demand (lactation) induce NPY expression in the hypothalamus (7,8); most genetic models of obesity exhibit hyperphagia and an increase in hypothalamic NPY levels (9)(10)(11)(12)(13); and various pharmacological treatments that enhance feeding are accompanied by an increase in NPY (14). In addition, various methods (antisense oligonucleotides, antibodies, or receptor antagonists) aimed at blocking NPY actions in the hypothalamus have been shown to inhibit feeding (15)(16)(17)(18)(19)(20)(21)(22).…”

mentioning

confidence: 99%

Modulation of neuropeptide Y expression in adult mice does not affect feeding

Marie

Luquet²,

Cole³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Despite numerous experiments showing that administration of neuropeptide Y (NPY) to rodents stimulates feeding and obesity, whereas acute interference with NPY signaling disrupts feeding and promotes weight loss, NPY-null mice have essentially normal body weight regulation. These conflicting observations suggest that chronic lack of NPY during development may lead to compensatory changes that normalize regulation of food intake and energy expenditure in the absence of NPY. To test this idea, we used gene targeting to introduce a doxycycline (Dox)-regulated cassette into the Npy locus, such that NPY would be expressed until the mice were given Dox, which blocks transcription. Compared with wild-type mice, adult mice bearing this construct expressed Ϸ4-fold more Npy mRNA, which fell to Ϸ20% of control values within 3 days after treatment with Dox. NPY protein also fell Ϸ20-fold, but the half-life of Ϸ5 days was surprisingly long. The biological effectiveness of these manipulations was demonstrated by showing that overexpression of NPY protected against kainateinduced seizures. Mice chronically overexpressing NPY had normal body weight, and administration of Dox to these mice did not suppress feeding. Furthermore, the refeeding response of these mice after a fast was normal. We conclude that, if there is compensation for changes in NPY levels, then it occurs within the time it takes for Dox treatment to deplete NPY levels. These observations suggest that pharmacological inhibition of NPY signaling is unlikely to have long-lasting effects on body weight. body weight regulation ͉ conditional knockout ͉ feeding behavior N umerous studies using a variety of approaches have implicated neuropeptide Y (NPY) in the regulation of body weight. Injection of NPY or NPY-related peptides intracranially (either into the hypothalamus or cerebral ventricles) stimulates robust feeding (1-6); conditions of energy deprivation (starvation) or increased energy demand (lactation) induce NPY expression in the hypothalamus (7,8); most genetic models of obesity exhibit hyperphagia and an increase in hypothalamic NPY levels (9-13); and various pharmacological treatments that enhance feeding are accompanied by an increase in NPY (14). In addition, various methods (antisense oligonucleotides, antibodies, or receptor antagonists) aimed at blocking NPY actions in the hypothalamus have been shown to inhibit feeding (15)(16)(17)(18)(19)(20)(21)(22). Moreover, there is anatomical and electrophysiological evidence that NPY neurons in the arcuate (ARC) region of the hypothalamus have direct inhibitory inputs onto proopiomelanocortin (POMC) cells that form part of the melanocortin-signaling pathway, which suppresses feeding (23). Thus, current models for hypothalamic control of energy balance suggest that activation of POMC cell signaling to cells bearing melanocortin-4 receptors (MC4R) suppresses feeding, whereas NPY and various other hormones and neurotransmitters stimulate feeding by antagonizing this melanocortin-signaling pathway. NPYexpressing n...

show abstract

“…Structure-function analyses of these peptides' feeding stimulatory effects reveal pharmacological specificity in terms of the amino acid sequence required for efficacy. These studies show the critical amino acid sequence for NPY to be theN-terminalamino acids 1-12 (79,165). For GAL,theyare the first 16 N-terminal amino acids (48).…”

Section: Physiological and Behavioral Effects Of Brain Peptidesmentioning

confidence: 96%

Brain Peptides and Obesity: Pharmacologic Treatment

Leibowitz

1995

Obesity Research

104

View full text Add to dashboard Cite

LEIBOWITZ, SARAH F. Brain peptides and obesity: pharmacologic treatment. ObesRes. 1995;3(Supp14):573S-5893. Obesity results from an imbalance between nutrient ingestion andmetabolism,withmore calories being ingested than utilized. Thebrain plays animportant roleincoordinating these complex behavioral and physiologicalfunctions, operating through multiple neurochemical systems with distinct properties. This review focuses on two hypothalamicpeptide systems, neuropeptide Y (NPY) and galanin (GAL), that illustrate how the brain operates through different mechanisms to control the body's nutrient stores, in different states o r conditions. These peptides have different behavioralandphysiologicaleffects andare,themselves,differentially responsive to feedback signals from circulating steroids,peptides,and nutrients. They canbedistinguishedby their relation to natural feeding patterns and endogenous hormones and by their specificity of action in relation to natural biological rhythms.Theneuroanatomicalsubstrates involved in these actionsaf NPY and GAL are also distinct. The neurocircuit mediating NPY's actions originates in the arcuatenucleus and terminates in the medial portion of the paraventricular nucleus; the GAGcontaining neurons, in contrast, are concentrated in the lateral portion of the paraventricular nucleus, in addition to the medial preoptic area, which contribute to 1ocalGALinnervation as wellas projections to the median eminence. Regarding their distinct functions, the evidence suggests that the NPY system is more closely related to patterns of carbohydrate ingestion andcarbohydrate utilization, channeling nutrients towards the synthesisoffat. Itismost strongly activatedatthestartoftheactive feeding cycle or afterweaning,in close association with the adrenal steroid,corticosterone. The GAL system,in contrast, is more closely associated with patterns of fat consumption and signals related to fat oxidation. This peptide systemis most active duringthemiddleof the feeding cycle or immediately afterpuberty,in close associationwith the gonadal steroids. The gene expression and synthesis of these peptides in their respective neuronal cell groups is inhibited by circulating insulin and altered by dietary nutriFrom the Rockefeller University, New York, NY

show abstract

Structure-function analysis of stimulation of food intake by neuropeptide Y: Effects of receptor agonists

Cited by 132 publications

References 23 publications

Central neuropeptide Y induces proximal stomach relaxation via Y1 receptors in the dorsal vagal complex of the rat

Central neuropeptide Y induces proximal stomach relaxation via Y1 receptors in the dorsal vagal complex of the rat

Modulation of neuropeptide Y expression in adult mice does not affect feeding

Brain Peptides and Obesity: Pharmacologic Treatment

Contact Info

Product

Resources

About