[D-Trp34] neuropeptide Y is a potent and selective neuropeptide Y Y5 receptor agonist with dramatic effects on food intake☆

Parker, Eric M.; Balasubramaniam, Ambikaipakan; Guzzi, M.; Mullins, Deborra; Salisbury, Brian; Sheriff, Sulaiman; Witten, Melanie; Hwa, Joyce

doi:10.1016/s0196-9781(00)00156-x

Cited by 78 publications

(50 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The importance of the Y5 receptor is indicated by several different lines of evidence, including the injection of Y5 antisense oligonucleotides (Schaffhauser et al 1997;Tang-Christensen et al 1998;Flynn et al 1999;Campbell et al 2001), the injection of specific Y5 agonists (Haynes et al 1998;Wyss et al 1998a,b;Cabrele et al 2000;Parker et al 2000;Lecklin et al 2003) and antagonists (Polidori et al 2000;Kask et al 2001;Yokosuka et al 2001;Daniels et al 2002). In contrast, several studies have suggested a minor role of the Y5 receptor in feeding behaviour.…”

Section: Npy and Normal Feeding Behaviourmentioning

confidence: 99%

Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

Beck

2006

Phil. Trans. R. Soc. B

209

129

View full text Add to dashboard Cite

Neuropeptide Y (NPY) is one the most potent orexigenic peptides found in the brain. It stimulates food intake with a preferential effect on carbohydrate intake. It decreases latency to eat, increases motivation to eat and delays satiety by augmenting meal size. The effects on feeding are mediated through at least two receptors, the Y1 and Y5 receptors. The NPY system for feeding regulation is mostly located in the hypothalamus. It is formed of the arcuate nucleus (ARC), where the peptide is synthesized, and the paraventricular (PVN), dorsomedial (DMN) and ventromedial (VMN) nuclei and perifornical area where it is active. This activity is modulated by the hindbrain and limbic structures. It is dependent on energy availability, e.g. upregulation with food deprivation or restriction, and return to baseline with refeeding. It is also sensitive to diet composition with variable effects of carbohydrates and fats. Leptin signalling and glucose sensing which are directly linked to diet type are the most important factors involved in its regulation. Absence of leptin signalling in obesity models due to gene mutation either at the receptor level, as in the Zucker rat, the Koletsky rat or the db/db mouse, or at the peptide level, as in ob/ob mouse, is associated with increased mRNA abundance, peptide content and/or release in the ARC or PVN. Other genetic obesity models, such as the Otsuka-Long-Evans-Tokushima Fatty rat, the agouti mouse or the tubby mouse, are characterized by a diminution in NPY expression in the ARC nucleus and by a significant increase in the DMN. Further studies are necessary to determine the exact role of NPY in these latter models. Long-term exposure to high-fat or high-energy palatable diets leads to the development of adiposity and is associated with a decrease in hypothalamic NPY content or expression, consistent with the existence of a counter-regulatory mechanism to diminish energy intake and limit obesity development. On the other hand, an overactive NPY system (increased mRNA expression in the ARC associated with an upregulation of the receptors) is characteristic of rats or rodent strains sensitive to dietary-induced obesity. Finally, NPY appears to play an important role in body weight and feeding regulation, and while it does not constitute the only target for drug treatment of obesity, it may nevertheless provide a useful target in conjunction with others.

show abstract

Section: Npy and Normal Feeding Behaviourmentioning

confidence: 99%

Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

Beck

2006

Phil. Trans. R. Soc. B

209

129

View full text Add to dashboard Cite

show abstract

“…NPY Y5 receptor antagonists also inhibit food intake, but surprisingly have no effect on NPY-induced feeding responses, 38 raising questions about the role of Y5 in NPY's feeding effects. However, NPY Y5 receptor selective agonists stimulate feeding 39,40 and NPY Y5-deficient mice do have blunted feeding in response to NPY. 41 Taken together, these data suggest a role for both Y1 and Y5 receptors in the orexigenic actions of NPY.…”

Section: Neuropeptide Ymentioning

confidence: 99%

The NPY/AgRP neuron and energy homeostasis

2001

View full text Add to dashboard Cite

Kennedy hypothesized nearly 50 y ago that negative feedback regulation of body fat stores involves hormones that circulate in proportion to adiposity and enter the brain, where they exert inhibitory effects on food intake and energy balance. Recent studies implicate leptin and insulin as 'adiposity signals' to the brain that promote negative energy balance in two ways: by inhibiting 'anabolic' hypothalamic neuronal circuits that stimulate food intake and promote weight gain, and by activating 'catabolic' pathways that reduce food intake and body weight. Chief among candidate 'anabolic' effector pathways is the NPY=AgRP neuron, found only in the hypothalamic arcuate nucleus. These neurons make peptides that potently stimulate food intake not only by increasing neuropeptide Y (NPY) signaling, but by reducing melanocortin signaling via the release of agoutirelated peptide (AgRP), an endogenous melanocortin 3=4 receptor antagonist. Since NPY=AgRP neurons express receptors for leptin and insulin and are inhibited by these hormones, they are activated by a decrease of leptin or insulin signaling. Fasting, uncontrolled diabetes, and genetic leptin deficiency are examples of conditions in which food intake increases via a mechanism hypothesized to involve NPY=AgRP neurons. Data are reviewed which illustrate the role of these neurons in adaptive and maladaptive states characterized by hyperphagia and weight gain.

show abstract

“…[D-Trp 34 ]-NPY (Parker et al, 2000) potently increased de novo protein synthesis to a similar extent to NPY in SHR cardiomyocytes at 16 weeks. Taken together with lack of antagonism of responses to PYY 3-36 and NPY by BIIE-0246 (Doods et al, 1999;King et al, 2000; Table 2), these data support a role for NPY Y 5 receptors, rather than NPY Y 2 receptors, in enhanced protein synthesis.…”

Section: Discussionmentioning

confidence: 94%

“…[Leu 31 Pro 34 ]-NPY is an agonist with high affinity for NPY Y 1 , Y 4 , and Y 5 receptors but devoid of activity at NPY Y 2 receptors, whereas peptide YY ) is selective for NPY Y 2 and NPY Y 5 receptors relative to other NPY Y receptor subtypes (Michel et al, 1997). ]-NPY (Parker et al, 2000) and [Ala 31 ,Aib 32 ]-NPY are potent and selective NPY Y 5 receptor agonists, whereas WX-143-B is a highly selective agonist at NPY Y 4 receptors (Balasubramaniam et al, 2001). More recently, development of nonpeptide NPY Y receptor antagonists has assisted greatly in receptor classification .…”

mentioning

confidence: 99%

Induction of Hypertrophic Responsiveness of Cardiomyocytes to Neuropeptide Y in Response to Pressure Overload

Bell

Allen²,

Kelso³

et al. 2002

J Pharmacol Exp Ther

Self Cite

View full text Add to dashboard Cite

To determine whether neuropeptide Y (NPY)-related mechanisms become activated with progression of cardiac hypertrophy in vivo, protein mass and de novo protein synthesis (incorporation of [14 C]Phe, 0.1 Ci ml Ϫ1 ) were assessed in cardiomyocytes, obtained from spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (8, 12, 16, 20, and 24 weeks of age), and cultured for 24 h. NPY (10 Ϫ8 M) increased protein mass of cardiomyocytes from 16-week-old SHRs by 9.2 Ϯ 2.1% (n ϭ 8, P Ͻ 0.05). De novo protein synthesis was increased maximally in SHRs at 12, 16, and 20 weeks (P Ͻ 0.05, n ϭ 8) in response to NPY by 12.6 Ϯ 2.1% (10 Ϫ6 M), 20.1 Ϯ 4.2% (10 Ϫ8 M), and 9.4 Ϯ 1.8% (10 Ϫ7 M), respectively. Peptide YY 3-36 ,

show abstract

[D-Trp34] neuropeptide Y is a potent and selective neuropeptide Y Y5 receptor agonist with dramatic effects on food intake☆

Cited by 78 publications

References 22 publications

Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

Neuropeptide Y in normal eating and in genetic and dietary-induced obesity

The NPY/AgRP neuron and energy homeostasis

Induction of Hypertrophic Responsiveness of Cardiomyocytes to Neuropeptide Y in Response to Pressure Overload

Contact Info

Product

Resources

About