Neuropeptide Y

Last updated
NPY
3D represantation of human Neuropeptide Y.png
Available structures
PDB Ortholog search: PDBe RCSB
Identifiers
Aliases NPY , PYY4, Neuropeptid Y gene, neuropeptide Y
External IDs OMIM: 162640 MGI: 97374 HomoloGene: 697 GeneCards: NPY
Orthologs
SpeciesHumanMouse
Entrez

4852

109648

Ensembl

ENSG00000122585

ENSMUSG00000029819

UniProt

P01303

P57774

RefSeq (mRNA)

NM_000905

NM_023456

RefSeq (protein)

NP_000896

NP_075945

Location (UCSC) Chr 7: 24.28 – 24.29 Mb Chr 6: 49.8 – 49.81 Mb
PubMed search [3] [4]
Wikidata
View/Edit Human View/Edit Mouse
Neuropeptide Y
Identifiers
CAS Number
ChemSpider
  • none
UNII
ChEMBL
CompTox Dashboard (EPA)
Chemical and physical data
Formula C190H287N55O57
Molar mass 4253.714 g·mol−1
 X mark.svgNYes check.svgY  (what is this?)    (verify)

Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glutamate. [5] [6] [7] [8]  

Contents

In the autonomic system it is produced mainly by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue. [9] In the brain, it is produced in various locations including the hypothalamus, and is thought to have several functions, including: increasing food intake and storage of energy as fat, reducing anxiety and stress, reducing pain perception, affecting the circadian rhythm, reducing voluntary alcohol intake, lowering blood pressure, and controlling epileptic seizures. [8] [10]

Function

Neuropeptide Y has been identified as being synthesized in GABAergic neurons and to act as a neurotransmitter during cellular communication. Neuropeptide Y is expressed in interneurons. [11] NPY exerts most of its effects through Neuropeptide Y receptors, mainly Y1, Y2, Y4, and Y6. [7] [8] All receptors have been indicated as participants in post-synaptic transmission activity, but the Y2 receptor has also been found to be involved in pre-synaptic processing. [6]

The receptor protein that NPY operates on is a G protein-coupled receptor in the rhodopsin like 7-transmembrane GPCR family. Five subtypes of the NPY receptor have been identified in mammals, four of which are functional in humans. [12] Subtypes Y1 and Y5 have known roles in the stimulation of feeding while Y2 and Y4 seem to have roles in appetite inhibition (satiety). Some of these receptors are among the most highly conserved neuropeptide receptors [ citation needed ].

High concentrations of neuropeptide Y synthesis and action have been found in the hypothalamus and hippocampus, specifically in the arcuate nucleus (ARC) and dentate gyrus. The arcuate nucleus has been found to have one of the highest concentrations of NPY. This allows NPY to regulate neuroendocrine release of various hypothalamic hormones such as luteinizing hormone. [13] Neuropeptide Y1 receptors have been found in highest density in the dentate gyrus along with a variety of other brain areas. [14]

NPY is able to modulate the mitochondrial network by affecting the expression of many genes involved in mitochondrial functions and dynamics. It has been found that in breast muscle, ATP production genes (uncoupling protein, UCP; nuclear factor erythroid 2 like 2, NFE2L2) and a dynamics gene (mitofusin 1, MFN1) were upregulated (P < 0.05) at a low dose of NPY, while a high dose decreased (P < 0.05) markers of mitochondrial dynamics (mitofusin 2, MFN2; OPA1 mitochondrial dynamin-like GTPase, OPA1) and increased (P < 0.05) genes involved in mitochondrial biogenesis (D-loop, peroxisome proliferator-activated receptor gamma, PPARG). [15]

Cell growth

Neuropeptide Y has been indicated as playing an important role in neurogenesis in various parts of the brain. Two particular brain areas where NPY affects neurogenesis are the sub-ventricular zone and the dentate gyrus of the hippocampus. These areas are where cell growth and proliferation occur into adulthood. [16]

Dentate gyrus

The dentate gyrus is significantly involved in cell proliferation, a process modulated by various internal factors including neuropeptide Y. Reduction or elimination of NPY released by interneurons decreased cell growth in this brain area. NPY affects neurogenesis by interacting with ERK kinase signaling pathways. [17] Additionally, NPY acting on and stimulating Y1 receptors present on progenitor cell membranes in order to increase cell proliferation. [16]

Sub-ventricular zone

Similar to the dentate gyrus, NPY has been found to increase cellular proliferation and differentiation in the sub-ventricular zone by specifically activating Y1 receptors in the ERK1/2 pathway. Additionally, NPY was found in neuronal fibers that pass through the sub-ventricular zone and extend to other brain areas. A variety of other effects and physiological processes involving NPY in the sub-ventricular zone have been discovered, many of which involve neuron migration patterns. [18]

Olfactory bulb

It was found that after blocking NPY expression in mouse olfactory epithelium, the amount of olfactory precursor cells decreased by half. This in turn caused the mice to develop a lower amount of olfactory cells overall. This study exemplified NPY's influence on precursor cells. [19]

Discovery

Following the isolation of neuropeptide Y (NPY) from the porcine hypothalamus in 1982, researchers began to speculate about the involvement of NPY in hypothalamic-mediated functions. In a 1983 study, NPY-ergic axon terminals were located in the paraventricular nucleus (PVN) of the hypothalamus, and the highest levels of NPY immunoreactivity was found within the PVN of the hypothalamus. [20]

Six years later, in 1989, Morris et al. homed in on the location of NPYergic nuclei in the brain. Furthermore, in situ hybridization results from the study showed the highest cellular levels of NPY mRNA in the arcuate nucleus (ARC) of the hypothalamus. [21]

In 1989, Haas & George reported that local injection of NPY into the PVN resulted in an acute release of corticotropin-releasing hormone (CRH) in the rat brain, proving that NPYergic activity directly stimulates the release and synthesis of CRH. [22]

The latter became a hallmark paper in NPY studies. A significant amount of work had already been done in the 1970s on CRH and its involvement in stress and eating disorders such as obesity. [23] These studies, collectively, marked the beginning for understanding the role of NPY in orexigenesis or food intake.

Connection to food intake

Behavioral assays in orexigenic studies, in which rats are the model organism, have been done collectively with immunoassays and in situ hybridization studies to confirm that elevating NPY-ergic activity does indeed increase food intake. In these studies, exogenous NPY, [24] the glucocorticoid dexamethasone (which activates NPY in the basomedial hypothalamus), [25] or N-acetyl [Leu 28, Leu31] NPY (24-36) [26] are injected into the third ventricle [24] or at the level of the hypothalamus with a cannula. [25] [27]

Furthermore, these studies unanimously demonstrate that the stimulation of NPYergic activity via the administration of certain NPY agonists increases food intake compared to baseline data in rats. The effects of NPYergic activity on food intake is also demonstrated by the blockade of certain NPY receptors (Y1 and Y5 receptors), which, as was expected, inhibited NPYergic activity; thus, decreases food intake. However, a 1999 study by King et al. demonstrated the effects of the activation of the NPY autoreceptor Y2, which has been shown to inhibit the release of NPY and thus acts to regulate food intake upon its activation. [28] In this study a highly selective Y2 antagonist, BIIE0246 was administered locally into the ARC. Radioimmunoassay data, following the injection of BIIE0246, shows a significant increase in NPY release compared to the control group. Though the pharmacological half-life of exogenous NPY, other agonists, and antagonist is still obscure, the effects are not long lasting and the rat body employs an excellent ability to regulate and normalize abnormal NPY levels and therefore food consumption. [24]

Connection to obesity

A study in genetically obese rats demonstrated the role of NPY in obesity. [29] Four underlying factors that contribute to obesity in rats are:

In obesity chronically elevated levels of NPY can be seen, this has been seen in rats fed on a high fat diet for 22 weeks and resulted in a hormonal derangement that increased NPY release, due to a defective leptin signal compared to control rats. In humans increased levels of free NPY were found in obese women and not in their leaner counterparts, analysing human hypothalamus' for NPY concentration however is more difficult than rats. [31] During weaning in rats there is an early expression of gene mutations that increase hypothalamic release of NPY in rats, however in humans multiple genes are commonly associated with the results of obesity and metabolic syndrome. [31] In most obesity cases the increased secretion of NPY is a central / hypothalamic resistance to energy excess hormone signals such as leptin, that can be a result of a variety of reasons in the CNS. In rodents resistant to obesity when fed on an obesogenic diet they had a significantly lower amount of NPY receptor in the hypothalamus suggesting an increased activity of NPY neurons in obese rats meaning that the reduction in the release of NPY may be beneficial to the reduction of obesity incidence alongside the consumption of a healthy diet and exercise. This would need to be seen in human research before looking at this avenue of weight loss although currently there is some evidence that suggests NPY is a significant predictor in weight regain after weight loss to maintain old levels of energy storage. [31]

Furthermore, these factors correlate with each other. The sustained high levels of glucocorticosteroids stimulate gluconeogenesis, which subsequently causes an increase of blood glucose that activates the release of insulin to regulate glucose levels by causing its reuptake and storage as glycogen in the tissues in the body. In the case of obesity, which researchers speculate to have a strong genetic and a dietary basis, insulin resistance prevents high blood glucose regulation, resulting in morbid levels of glucose and diabetes mellitus. [32] In addition, high levels of glucocorticosteroids causes an increase of NPY by directly activating type II glucocorticosteroids receptors (which are activated only by relatively high levels of glucocorticosteroids) and, indirectly, by abolishing the negative feedback of corticotropin-releasing factor (CRF) on NPY synthesis and release. Meanwhile, obesity-induced insulin resistance and the mutation of the leptin receptor (ObRb) results in the abolition of inhibition of NPYergic activity and ultimately food intake via other negative feedback mechanisms to regulate them. Obesity in rats was significantly reduced by adrenalectomy [33] or hypophysectomy. [34]

A study showed that neuropeptide Y can be used as a biosensor in early detection of childhood obesity [35]

Clinical significance

Alcoholism

The role of neuropeptide Y has gained substantial attention for its involvement with alcoholism due to its diverse range of physiological effects. [36] NPY neurons have been shown to interact with dopaminergic reward and emotion pathways in the nucleus accumbens and amygdala, respectively. NPY expression levels and alcohol preference have been shown to exhibit an inverse relationship. Expression levels are dependent on the brain area of interest. This indicates that baseline NPY levels could possibly influence innate alcohol preferences. [7]

Previous studies have identified NPY's anxiolytic effects to a possible therapeutic drug target for alcoholism. [37] As stated before, NPY levels and ethanol intake show an inverse relationship, therefore, increasing NPY availability could decrease alcohol intake. By creating a chemical antagonist for a Y2 receptor that would indirectly act as an agonist and stimulate Y1 receptors, alcohol consumption was successfully decreased in rats. [36] Additionally, another similar study identified that NPY expression may be connected to behavioral regulation in relation to alcohol dependence. Administration of neuropeptide Y was found to reduce binge-drinking behavior. [38] Although, it has been shown that NPY gene expression, mRNA or neuropeptide levels are not influenced by long-term alcohol consumption, but changes do occur during withdrawal from alcohol. These findings show that neuropeptide Y has varying effects on alcohol consumption. [36]

Two results suggest that NPY might protect against alcoholism:

Stress and anxiety

Neuropeptide Y is considered to be an anxiolytic endogenous peptide and its levels can be modulated by stress. NPY has connections to the HPA axis and is believed to be necessary for stress modulation. [41] It has been shown that higher levels of the Y1 and Y5 receptors in the amygdala result in reduced level of anxiety. [42] Additionally, the Y1 receptor has been linked to anxiolytic effects in the forebrain while Y2 has been associated with the pons. [11]

Conversely, higher levels of NPY may be associated with resilience against and recovery from posttraumatic stress disorder [43] and with dampening the fear response, allowing individuals to perform better under extreme stress. [44]

Studies of mice and monkeys show that repeated stress—and a high-fat, high-sugar diet—stimulate the release of neuropeptide Y, causing fat to build up in the abdomen. Researchers believe that by manipulating levels of NPY, they could eliminate fat from areas where it was not desired and accumulate at sites where it is needed. [9] [45]

See also

Related Research Articles

<span class="mw-page-title-main">Hypothalamus</span> Area of the brain below the thalamus

The hypothalamus is a part of the brain that contains a number of small nuclei with a variety of functions. One of the most important functions is to link the nervous system to the endocrine system via the pituitary gland. The hypothalamus is located below the thalamus and is part of the limbic system. In the terminology of neuroanatomy, it forms the ventral part of the diencephalon. All vertebrate brains contain a hypothalamus. In humans, it is the size of an almond.

<span class="mw-page-title-main">Leptin</span> Hormone that inhibits hunger

Leptin is a hormone predominantly made by adipose cells and its primary role is likely to regulate long-term energy balance.

<span class="mw-page-title-main">Orexin</span> Neuropeptide that regulates arousal, wakefulness, and appetite.

Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, type 1, in which the individual experiences brief losses of muscle tone, is caused by a lack of orexin in the brain due to destruction of the cells that produce it. It exists in the forms of orexin-A and orexin-B.

<span class="mw-page-title-main">Paraventricular nucleus of hypothalamus</span>

The paraventricular nucleus is a nucleus in the hypothalamus. Anatomically, it is adjacent to the third ventricle and many of its neurons project to the posterior pituitary. These projecting neurons secrete oxytocin and a smaller amount of vasopressin, otherwise the nucleus also secretes corticotropin-releasing hormone (CRH) and thyrotropin-releasing hormone (TRH). CRH and TRH are secreted into the hypophyseal portal system and act on different targets neurons in the anterior pituitary. PVN is thought to mediate many diverse functions through these different hormones, including osmoregulation, appetite, and the response of the body to stress.

Dynorphins (Dyn) are a class of opioid peptides that arise from the precursor protein prodynorphin. When prodynorphin is cleaved during processing by proprotein convertase 2 (PC2), multiple active peptides are released: dynorphin A, dynorphin B, and α/β-neo-endorphin. Depolarization of a neuron containing prodynorphin stimulates PC2 processing, which occurs within synaptic vesicles in the presynaptic terminal. Occasionally, prodynorphin is not fully processed, leading to the release of “big dynorphin.” “Big Dynorphin” is a 32-amino acid molecule consisting of both dynorphin A and dynorphin B.

<span class="mw-page-title-main">Arcuate nucleus</span>

The arcuate nucleus of the hypothalamus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. These neurons, generated from the ventral part of the periventricular epithelium during embryonic development, locate dorsally in the hypothalamus, becoming part of the ventromedial hypothalamic region. The function of the arcuate nucleus relies on its diversity of neurons, but its central role is involved in homeostasis. The arcuate nucleus provides many physiological roles involved in feeding, metabolism, fertility, and cardiovascular regulation.

<span class="mw-page-title-main">Ghrelin</span> Peptide hormone involved in appetite regulation

Ghrelin is a hormone produced by enteroendocrine cells of the gastrointestinal tract, especially the stomach, and is often called a "hunger hormone" because it increases the drive to eat. Blood levels of ghrelin are highest before meals when hungry, returning to lower levels after mealtimes. Ghrelin may help prepare for food intake by increasing gastric motility and stimulating the secretion of gastric acid.

<span class="mw-page-title-main">Agouti-related peptide</span> Mammalian protein found in Homo sapiens

Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. In humans, the agouti-related peptide is encoded by the AGRP gene.

<span class="mw-page-title-main">Ventromedial nucleus of the hypothalamus</span> Nucleus of the hypothalamus

The ventromedial nucleus of the hypothalamus is a nucleus of the hypothalamus. In 2007, Kurrasch et al. found that the ventromedial hypothalamus is a distinct morphological nucleus involved in terminating hunger, fear, thermoregulation, and sexual activity. This nuclear region is involved in the recognition of the feeling of fullness.

The periventricular nucleus is a thin sheet of small neurons located in the wall of the third ventricle, a composite structure of the hypothalamus. It functions in analgesia.

Nesfatin-1 is a neuropeptide produced in the hypothalamus of mammals. It participates in the regulation of hunger and fat storage. Increased nesfatin-1 in the hypothalamus contributes to diminished hunger, a 'sense of fullness', and a potential loss of body fat and weight.

<span class="mw-page-title-main">Growth hormone secretagogue receptor</span> Protein-coding gene in the species Homo sapiens

Growth hormone secretagogue receptor(GHS-R), also known as ghrelin receptor, is a G protein-coupled receptor that binds growth hormone secretagogues (GHSs), such as ghrelin, the "hunger hormone". The role of GHS-R is thought to be in regulating energy homeostasis and body weight. In the brain, they are most highly expressed in the hypothalamus, specifically the ventromedial nucleus and arcuate nucleus. GSH-Rs are also expressed in other areas of the brain, including the ventral tegmental area, hippocampus, and substantia nigra. Outside the central nervous system, too, GSH-Rs are also found in the liver, in skeletal muscle, and even in the heart.

Neuromedin U is a neuropeptide found in the brain of humans and other mammals, which has a number of diverse functions including contraction of smooth muscle, regulation of blood pressure, pain perception, appetite, bone growth, and hormone release. It was first isolated from the spinal cord in 1985, and named after its ability to cause smooth muscle contraction in the uterus.

<span class="mw-page-title-main">Neuropeptide Y receptor Y5</span> Protein-coding gene in the species Homo sapiens

Neuropeptide Y receptor type 5 is a protein that in humans is encoded by the NPY5R gene.

The central melanocortin system is defined anatomically as a collection of central nervous system circuits which include:

Galanin-like peptide (GALP) is a neuropeptide present in humans and other mammals. It is a 60-amino acid polypeptide produced in the arcuate nucleus of the hypothalamus and the posterior pituitary gland. It is involved in the regulation of appetite and may also have other roles such as in inflammation, sex behavior, and stress.

Hunger is a sensation that motivates the consumption of food. The sensation of hunger typically manifests after only a few hours without eating and is generally considered to be unpleasant. Satiety occurs between 5 and 20 minutes after eating. There are several theories about how the feeling of hunger arises. The desire to eat food, or appetite, is another sensation experienced with regards to eating.

Ingestive behaviors encompass all eating and drinking behaviors. These actions are influenced by physiological regulatory mechanisms; these mechanisms exist to control and establish homeostasis within the human body. Disruptions in these ingestive regulatory mechanisms can result in eating disorders such as obesity, anorexia, and bulimia.

<span class="mw-page-title-main">Central nucleus of the amygdala</span> Nucleus within the amygdala

The central nucleus of the amygdala is a nucleus within the amygdala. It "serves as the major output nucleus of the amygdala and participates in receiving and processing pain information."

<span class="mw-page-title-main">Jessica Barson</span> American neuroscientist

Jessica Barson is an American neuroscientist and associate professor at Drexel University College of Medicine. Barson investigates neuropeptide signalling in the paraventricular nucleus of the thalamus as well as the nucleus accumbens to understand the neurobiological basis of addiction and elucidate targets for therapy.

References

  1. 1 2 3 GRCh38: Ensembl release 89: ENSG00000122585 - Ensembl, May 2017
  2. 1 2 3 GRCm38: Ensembl release 89: ENSMUSG00000029819 - Ensembl, May 2017
  3. ↑ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  4. ↑ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
  5. ↑ Heilig M, Widerlöv E (1995). "Neurobiology and clinical aspects of neuropeptide Y". Critical Reviews in Neurobiology. 9 (2–3): 115–136. PMID   8581979.
  6. 1 2 Decressac M, Barker RA (December 2012). "Neuropeptide Y and its role in CNS disease and repair". Experimental Neurology. 238 (2): 265–272. doi:10.1016/j.expneurol.2012.09.004. PMID   23022456. S2CID   15088613.
  7. 1 2 3 Robinson SL, Thiele TE (2017). "The Role of Neuropeptide Y (NPY) in Alcohol and Drug Abuse Disorders". The Role of Neuropeptides in Addiction and Disorders of Excessive Consumption. International Review of Neurobiology. Vol. 136. pp. 177–197. doi:10.1016/bs.irn.2017.06.005. ISBN   9780128124734. PMID   29056151.
  8. 1 2 3 Tatemoto K (2004). "Neuropeptide Y and Related Peptides". In Michel MC (ed.). Neuropeptide Y: History and Overview. Handbook of Experimental Pharmacology. Vol. 162. Springer. pp. 2–15. ISBN   9783540405818.
  9. 1 2 Kuo LE, Kitlinska JB, Tilan JU, Li L, Baker SB, Johnson MD, et al. (July 2007). "Neuropeptide Y acts directly in the periphery on fat tissue and mediates stress-induced obesity and metabolic syndrome". Nature Medicine. 13 (7): 803–811. doi:10.1038/nm1611. PMID   17603492. S2CID   25675166.
  10. ↑ Colmers WF, El Bahh B (March 2003). "Neuropeptide Y and Epilepsy". Epilepsy Currents. 3 (2): 53–58. doi:10.1046/j.1535-7597.2003.03208.x. PMC   321170 . PMID   15309085.
  11. 1 2 Kask A, Harro J, von Hörsten S, Redrobe JP, Dumont Y, Quirion R (May 2002). "The neurocircuitry and receptor subtypes mediating anxiolytic-like effects of neuropeptide Y". Neuroscience and Biobehavioral Reviews. 26 (3): 259–283. doi:10.1016/s0149-7634(01)00066-5. PMID   12034130. S2CID   34688422.
  12. ↑ Michel MC, Beck-Sickinger A, Cox H, Doods HN, Herzog H, Larhammar D, et al. (March 1998). "XVI. International Union of Pharmacology recommendations for the nomenclature of neuropeptide Y, peptide YY, and pancreatic polypeptide receptors". Pharmacological Reviews. 50 (1): 143–150. PMID   9549761.
  13. ↑ Acuna-Goycolea C, Tamamaki N, Yanagawa Y, Obata K, van den Pol AN (August 2005). "Mechanisms of neuropeptide Y, peptide YY, and pancreatic polypeptide inhibition of identified green fluorescent protein-expressing GABA neurons in the hypothalamic neuroendocrine arcuate nucleus". The Journal of Neuroscience. 25 (32): 7406–7419. doi: 10.1523/jneurosci.1008-05.2005 . PMC   6725307 . PMID   16093392.
  14. ↑ Kautz M, Charney DS, Murrough JW (May 2017). "Neuropeptide Y, resilience, and PTSD therapeutics". Neuroscience Letters. 649: 164–169. doi:10.1016/j.neulet.2016.11.061. PMID   27913193. S2CID   3821043.
  15. ↑ Dhamad A, Zampiga M, Greene ES, Sirri F, Dridi S (September 2021). "Neuropeptide Y and its receptors are expressed in chicken skeletal muscle and regulate mitochondrial function". General and Comparative Endocrinology. 310: 113798. doi:10.1016/j.ygcen.2021.113798. PMID   33961876.
  16. 1 2 Decressac M, Wright B, David B, Tyers P, Jaber M, Barker RA, Gaillard A (March 2011). "Exogenous neuropeptide Y promotes in vivo hippocampal neurogenesis". Hippocampus. 21 (3): 233–238. doi:10.1002/hipo.20765. PMID   20095007. S2CID   4014094.
  17. ↑ Howell OW, Doyle K, Goodman JH, Scharfman HE, Herzog H, Pringle A, et al. (May 2005). "Neuropeptide Y stimulates neuronal precursor proliferation in the post-natal and adult dentate gyrus". Journal of Neurochemistry. 93 (3): 560–570. doi: 10.1111/j.1471-4159.2005.03057.x . PMID   15836615. S2CID   1531546.
  18. ↑ Malva JO, Xapelli S, Baptista S, Valero J, Agasse F, Ferreira R, Silva AP (December 2012). "Multifaces of neuropeptide Y in the brain--neuroprotection, neurogenesis and neuroinflammation". Neuropeptides. 46 (6): 299–308. doi:10.1016/j.npep.2012.09.001. PMID   23116540. S2CID   9366746.
  19. ↑ Hansel DE, Eipper BA, Ronnett GV (April 2001). "Neuropeptide Y functions as a neuroproliferative factor". Nature. 410 (6831): 940–944. Bibcode:2001Natur.410..940H. doi:10.1038/35073601. PMID   11309620. S2CID   4421740.
  20. ↑ Allen YS, Adrian TE, Allen JM, Tatemoto K, Crow TJ, Bloom SR, Polak JM (August 1983). "Neuropeptide Y distribution in the rat brain". Science. 221 (4613): 877–879. Bibcode:1983Sci...221..877A. doi:10.1126/science.6136091. PMID   6136091.
  21. ↑ Morris BJ (December 1989). "Neuronal localisation of neuropeptide Y gene expression in rat brain". The Journal of Comparative Neurology. 290 (3): 358–368. doi:10.1002/cne.902900305. PMID   2592617. S2CID   36876107.
  22. ↑ Haas DA, George SR (October 1989). "Neuropeptide Y-induced effects on hypothalamic corticotropin-releasing factor content and release are dependent on noradrenergic/adrenergic neurotransmission". Brain Research. 498 (2): 333–338. doi:10.1016/0006-8993(89)91112-8. PMID   2551461. S2CID   36802464.
  23. ↑ Edwardson JA, Hough CA (April 1975). "The pituitary-adrenal system of the genetically obese (ob/ob) mouse". The Journal of Endocrinology. 65 (1): 99–107. doi:10.1677/joe.0.0650099. PMID   167093.
  24. 1 2 3 Hanson ES, Dallman MF (April 1995). "Neuropeptide Y (NPY) may integrate responses of hypothalamic feeding systems and the hypothalamo-pituitary-adrenal axis". Journal of Neuroendocrinology. 7 (4): 273–279. doi:10.1111/j.1365-2826.1995.tb00757.x. PMID   7647769. S2CID   25471741.
  25. 1 2 White BD, Dean RG, Edwards GL, Martin RJ (May 1994). "Type II corticosteroid receptor stimulation increases NPY gene expression in basomedial hypothalamus of rats". The American Journal of Physiology. 266 (5 Pt 2): R1523–R1529. doi:10.1152/ajpregu.1994.266.5.R1523. PMID   8203629.
  26. ↑ King PJ, Widdowson PS, Doods HN, Williams G (August 1999). "Regulation of neuropeptide Y release by neuropeptide Y receptor ligands and calcium channel antagonists in hypothalamic slices". Journal of Neurochemistry. 73 (2): 641–646. doi: 10.1046/j.1471-4159.1999.0730641.x . PMID   10428060. S2CID   8022493.
  27. ↑ Pomonis JD, Levine AS, Billington CJ (July 1997). "Interaction of the hypothalamic paraventricular nucleus and central nucleus of the amygdala in naloxone blockade of neuropeptide Y-induced feeding revealed by c-fos expression". The Journal of Neuroscience. 17 (13): 5175–5182. doi: 10.1523/JNEUROSCI.17-13-05175.1997 . PMC   6573318 . PMID   9185555.
  28. ↑ King PJ, Williams G, Doods H, Widdowson PS (May 2000). "Effect of a selective neuropeptide Y Y(2) receptor antagonist, BIIE0246 on neuropeptide Y release". European Journal of Pharmacology. 396 (1): R1–R3. doi:10.1016/S0014-2999(00)00230-2. PMID   10822055.
  29. ↑ Beck B (July 2006). "Neuropeptide Y in normal eating and in genetic and dietary-induced obesity". Philosophical Transactions of the Royal Society of London. Series B, Biological Sciences. 361 (1471): 1159–1185. doi:10.1098/rstb.2006.1855. PMC   1642692 . PMID   16874931.
  30. ↑ Dryden S, Pickavance L, Frankish HM, Williams G (September 1995). "Increased neuropeptide Y secretion in the hypothalamic paraventricular nucleus of obese (fa/fa) Zucker rats". Brain Research. 690 (2): 185–188. doi:10.1016/0006-8993(95)00628-4. PMID   8535835. S2CID   1857168.
  31. 1 2 3 Minor RK, Chang JW, de Cabo R (February 2009). "Hungry for life: How the arcuate nucleus and neuropeptide Y may play a critical role in mediating the benefits of calorie restriction". Molecular and Cellular Endocrinology. 299 (1): 79–88. doi:10.1016/j.mce.2008.10.044. PMC   2668104 . PMID   19041366.
  32. ↑ Wilcox G (May 2005). "Insulin and insulin resistance". The Clinical Biochemist. Reviews. 26 (2): 19–39. PMC   1204764 . PMID   16278749.
  33. ↑ Yukimura Y, Bray GA (1978). "Effects of adrenalectomy on body weight and the size and number of fat cells in the Zucker (fatty) rat". Endocrine Research Communications. 5 (3): 189–198. doi:10.1080/07435807809083752. PMID   747998.
  34. ↑ Powley TL, Morton SA (April 1976). "Hypophysectomy and regulation of body weight in the genetically obese Zucker rat". The American Journal of Physiology. 230 (4): 982–987. doi:10.1152/ajplegacy.1976.230.4.982. PMID   1267030.
  35. ↑ Özcan B, Sezgintürk MK (December 2022). "Fabrication of an ultrasensitive and single-use graphite paper based immunosensor for Neuropeptide Y detection: A promising biosensing system for early detection of childhood obesity". Materials Today Communications. 33: 104797. doi:10.1016/j.mtcomm.2022.104797. S2CID   253229487.
  36. 1 2 3 Ciccocioppo R, Gehlert DR, Ryabinin A, Kaur S, Cippitelli A, Thorsell A, et al. (November 2009). "Stress-related neuropeptides and alcoholism: CRH, NPY, and beyond". Alcohol. 43 (7): 491–498. doi:10.1016/j.alcohol.2009.08.003. PMC   2804869 . PMID   19913192.
  37. ↑ Thorsell A, Mathé AA (2017). "Neuropeptide Y in Alcohol Addiction and Affective Disorders". Frontiers in Endocrinology. 8: 178. doi: 10.3389/fendo.2017.00178 . PMC   5534438 . PMID   28824541.
  38. ↑ Sparrow AM, Lowery-Gionta EG, Pleil KE, Li C, Sprow GM, Cox BR, et al. (May 2012). "Central neuropeptide Y modulates binge-like ethanol drinking in C57BL/6J mice via Y1 and Y2 receptors". Neuropsychopharmacology. 37 (6): 1409–1421. doi:10.1038/npp.2011.327. PMC   3327846 . PMID   22218088.
  39. ↑ Thiele TE, Koh MT, Pedrazzini T (February 2002). "Voluntary alcohol consumption is controlled via the neuropeptide Y Y1 receptor". The Journal of Neuroscience. 22 (3): RC208. doi: 10.1523/JNEUROSCI.22-03-j0006.2002 . PMC   6758511 . PMID   11826154.
  40. ↑ "Deprived of Sex, Jilted Flies Drink More Alcohol". UCSF News Center. March 15, 2012.
  41. ↑ Reichmann F, Holzer P (February 2016). "Neuropeptide Y: A stressful review". Neuropeptides. 55: 99–109. doi:10.1016/j.npep.2015.09.008. PMC   4830398 . PMID   26441327.
  42. ↑ Dumont Y, Quirion R (December 2014). "Neuropeptide Y pathways in anxiety-related disorders". Biological Psychiatry. 76 (11): 834–835. doi:10.1016/j.biopsych.2014.09.015. PMID   25439997. S2CID   38147315.
  43. ↑ Yehuda R, Brand S, Yang RK (April 2006). "Plasma neuropeptide Y concentrations in combat exposed veterans: relationship to trauma exposure, recovery from PTSD, and coping". Biological Psychiatry. 59 (7): 660–663. doi:10.1016/j.biopsych.2005.08.027. PMID   16325152. S2CID   33677746.
  44. ↑ Steenhuysen J (February 16, 2009). "Research shows why some soldiers are cool under fire". Archived from the original on February 19, 2009. Retrieved February 17, 2009.
  45. ↑ Maugh TH (July 2, 2007). "Research points to way to eliminate belly fat". Chicago Tribune .
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