Neuropeptide Y
Structure of Neuropeptide Y. From PDB 1ron. The Protein Data Bank ( PDB) is a repository for 3-D structural data of Proteins and Nucleic acids These data typically obtained by X-ray crystallography
Available structures: 1f8p, 1fvn, 1icy, 1ron
Identifiers
Symbol(s)	NPY; PYY4
External IDs	OMIM: 162640 MGI: 97374 HomoloGene: 697
RNA expression pattern
More reference expression data
Orthologs
	Human	Mouse
Entrez	4852	109648
Ensembl	ENSG00000122585	ENSMUSG00000029819
Uniprot	P01303	P57774
Refseq	NM_000905 (mRNA) NP_000896 (protein)	NM_023456 (mRNA) NP_075945 (protein)
Location	Chr 7: 24.29 - 24.3 Mb	Chr 6: 49.75 - 49.76 Mb
Pubmed search	[1]	[2]

Neuropeptide Y (NPY) is a 36 amino acid peptide neurotransmitter found in the brain and autonomic nervous system. The Human Genome Organisation (HUGO is an organization involved in the Human Genome Project, a project about mapping the human genome The Mouse Genome Informatics (MGI website is run by The Jackson Laboratory. HomoloGene, a tool of the National Center for Biotechnology Information (NCBI is a system for automated detection of homologs (similarity attributable to descent The Entrez Global Query Cross-Database Search System is a powerful Federated search engine or Web portal that allows users to search many discrete Health sciences Ensembl is a joint scientific project between the European Bioinformatics Institute and the Wellcome Trust Sanger Institute, which was launched in 1999 in response to the imminent UniProt is the uni versal prot ein resource a central repository of Protein data created by combining Swiss-Prot, TrEMBL PubMed is a free search engine for accessing the MEDLINE database of citations and abstracts of biomedical research articles In Chemistry, an amino acid is a Molecule containing both Amine and Carboxyl Functional groups In Biochemistry, this See Chemical synapse for an introduction to concepts and terminology used in this article The brain is the center of the Nervous system in animals All Vertebrates and the majority of Invertebrates have a brain &trade The autonomic nervous system ( ANS) (or visceral nervous system) is the part of the Peripheral nervous system that acts as a Control

NPY has been associated with a number of physiologic processes in the brain, including the regulation of energy balance, memory and learning, and epilepsy. ^[1] The main effect is increased food intake and decreased physical activity.

NPY is secreted by the hypothalamus, and in addition to increasing food intake, it increases the proportion of energy stored as fat and blocks nociceptive signals to the brain^[2]. The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis Nociception (synonym nociperception is defined as "the neural processes of encoding and processing Noxious stimuli.

NPY also augments the vasoconstrictor effects of noradrenergic neurons. Neurons (ˈnjuːɹɒn also known as neurones and nerve cells) are responsive cells in the Nervous system that process and transmit information

Contents 1 History 2 The role of NPY in food intake 3 The role of NPY in obesity 4 The role of NPY in anorexia nervosa 5 Correlation with stress and diet 6 Receptors 7 See also 8 References 9 External links

History

Following the isolation of neuropeptide-y (NPY) from the hypothalamus of porcine in 1982, researchers began to speculate the involvement of NPY in hypothalamic-mediated functions. The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis As more studies on the mysterious polypeptide began, the more of the big picture began to come into focus. Among these hallmark studies was a study done by Allen et al in 1983. One of the major findings in this study, appropriately entitled Neuropeptide Y distribution in the rat brain (1983), was the location of NPYergic axon terminals in the paraventricular nucleus (PVN) of the hypothalamus. The paraventricular nucleus (PVN is an aggregation of neurons in the Hypothalamus which produces many Hormones. The hypothalamus links the Nervous system to the Endocrine system via the Pituitary gland (hypophysis Moreover, Allen et al discovered the highest levels of NPY immunoreactivity within the PVN of the hypothalamus. ^[3].

Six years later, in 1989, Morris et al honed 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. In situ hybridization (ISH is a type of hybridization that uses a labeled Complementary DNA or RNA strand (i Messenger ribonucleic acid ( mRNA) is a molecule of RNA encoding a chemical "blueprint" for a Protein product The arcuate nucleus (or infundibular nucleus is an aggregation of Neurons in the mediobasal Hypothalamus, adjacent to the Third ventricle and the Median ^[4].

However, just two years earlier, in 1987, Haas & George conducted a study that involved injecting NPY locally and discovered an interesting result. Haas & George found that following a 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 CRF. Corticotropin-releasing hormone ( CRH) originally named corticotropin-releasing factor ( CRF) and also called corticoliberin, is a Polypeptide ^[5].

The latter became major hallmark study in NPY studies, because a significant amount of work had already been done around CRH in the 1970s, and its involvement in stress and eating disorders such as obesity^[6]. Obesity is a condition in which excess Body fat has accumulated to such an extent that health may be negatively affected These studies, collectively, marked the beginning of the role of NPY in orexigenesis or food intake.

The role of NPY in food intake

Behaviorial 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 NPYergic activity does indeed increase food intake. Rats are various medium sized long-tailed Rodents of the superfamily Muroidea In situ hybridization (ISH is a type of hybridization that uses a labeled Complementary DNA or RNA strand (i In these studies, exogenous NPY, ^[7] an NPY agonist such as dexamethasone ^[8], or N-acetyl [Leu 28, Leu31] NPY (24-36) ^[9] are injected into the third ventricle ^[10] or at the level of the hypothalamus with a cannula ^[11][12].

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. An agonist is a term used to describe a type of ligand or drug that binds and alters the activity of a receptor. The effects of NPYergic activity on food intake is also demonstrated by the blockade of certain NPY receptors (Y1 and Y5 receptors), which expectedly 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 ^[13]. 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 ^[14].

The role of NPY in obesity

Dryden et al, conducted a study in 1995 using genetically obese rats to demonstrate the in role of NPY in eating disorders such as obesity. Obesity is a condition in which excess Body fat has accumulated to such an extent that health may be negatively affected The study revealed four underlying factors that contributed to obesity in rats: 1. ) an increase in glucocorticosteriod concentrations in plasma; 2. ) insensitivity or resistance to insulin; 3. Insulin is a Hormone with intensive effects on both metabolism and several other body systems (eg vascular compliance ) mutation of leptin receptor; and, 4. In biology mutations are changes to the Nucleotide sequence of the Genetic material of an organism Leptin (Greek leptos meaning thin is a 16 kDa ) an increase in NPY mRNA and NPY release ^[15]. Furthermore, these factors are also correlates to each other. The sustained high levels of glucocorticosteriods stimulates 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 various tissues in the body. Gluconeogenesis (abreviated GNG) is a Metabolic pathway that results in the generation of Glucose from non- Carbohydrate carbon substrates such Glycogen is a Polysaccharide of Glucose (Glc which functions as the secondary short term energy storage in Animal cells 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, diabetes mellitus ^[16]. Diabetes mellitus (ˌdaɪəˈbiːtiːz or /ˌdaɪəˈbiːtəs/ /məˈlaɪtəs/ or /ˈmɛlətəs/ often referred to simply as diabetes ( Ancient Greek: grc Furthermore, high levels of glucocorticosteriods causes an increase of NPY by directly activating type II glucocorticosteriods receptors (which are only activated by relatively high levels of glucocorticosteriods) and indirectly, by abolishing the negative feedback of CRF on NPY synthesis and release. Meanwhile, obesity-induced insulin resistance and the mutation of the leptin receptor (ObRb) results in the abolishment of other negative feedback mechanisms to regulate NPYergic activity and ultimately food intake. Furthermore, obesity in rats was significantly reduced by adrenalectomy ^[17] and a hypophysectomy ^[18]

The role of NPY in anorexia nervosa

Kaye et al conducted a study in 1990 to demonstrate the role of NPY in anorexia nervosa. Anorexia Nervosa is a psychiatric Diagnosis that describes an Eating disorder characterized by low Body weight and Body image distortion In this post mortem study, high levels of NPY were found in the cerebrospinal fluid of patients with anorexia nervosa. An autopsy, also known as a post-mortem examination, necropsy, or obduction, is a Medical procedure that consists of a thorough Examination Cerebrospinal fluid ( CSF) Liquor cerebrospinalis, is a clear Bodily fluid that occupies the Subarachnoid space and the Ventricular system Subsequently, high concentrations of adrenacorticotropin hormone (ACTH) and cortisol in the plasma were also found in patients with anorexia nervosa ^[19]. Another study conducted seven years later revealed low levels of leptin, the hormone that inhibits NPY release at relatively high levels, were found to correlate with the extremely low levels of adipocytes in these patients; hence, the anxeriogenic nature of leptin^[20]. Leptin (Greek leptos meaning thin is a 16 kDa Furthermore, while the high levels of NPY increased food intake or hunger in patients with anorexia nervosa, the emotional discomfort associated with eating may explain the resistance to the orexigenic effects of NPY—suggesting a strong limbic system influence on food intake in eating disorder such as anorexia nervosa and bulimia nervosa ^[21]. The limbic system, or Paleomammalian brain is a term for a set of brain structures including the Hippocampus and Amygdala and anterior thalamic nuclei and a limbic Bulimia nervosa is an Eating disorder characterized by recurrent Binge eating, followed by compensatory behaviors referred to as "purging"

Correlation with stress and diet

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. A mouse (plural mice) is a small Animal that belongs to one A monkey is any member of either the New World monkeys or Old World monkeys two of the three groupings of Simian Primates the third group being Fats consist of a wide group of compounds that are generally soluble in organic solvents and largely insoluble in water Sugar is a class of edible Crystalline substances mainly Sucrose, Lactose, and Fructose. In Vertebrates such as Mammals the abdomen (belly constitutes the part of the body between the Thorax (chest and Pelvis. Researchers believe that by manipulating levels of the appetite hormone, they could make fat melt from areas where it was not desired and accumulate at sites where it is needed. ^[22][23]

Higher levels of NPY may be associated with resilience against and recovery from posttraumatic stress disorder. Resilience in Psychology is the positive capacity of people to Cope with stress and catastrophe. Post traumatic stress disorder It is a severe and ongoing emotional reaction to ^[24]

Receptors

Main article: Neuropeptide Y receptor

The receptor protein that NPY operates on is a G-protein coupled receptor in the rhodopsin like GPCR family. Neuropeptide Y receptors are a class of G-protein coupled receptors which are activated by the closely related peptide hormones Neuropeptide Y, Peptide YY G protein-coupled receptors ( GPCRs) also known as seven transmembrane domain receptors, 7TM receptors, heptahelical receptors, and Rhodopsin, also known as visual purple, is a Pigment of the Retina that is responsible for both the formation of the Photoreceptor cells and the These receptors are metabotropic, causing metabolic changes in the target cell rather than directly opening ion channels. Metabotropic receptor is a subtype of membrane receptors at the surface or in vesicles of Eukaryotic cells The protein contains seven membrane spanning domains and five subtypes have been identified in mammals, four of which are functional in humans. ^[25] 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.

See also

• Antianalgesia
• Neuropeptide
• Obesity
• Anorexia nervosa

References

External links

• EMBL receptor database entry
• MeSH Neuropeptide+Y

Medical Subject Headings ( MeSH) is a huge Controlled vocabulary (or metadata system for the purpose of indexing journal articles and books

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