Evolution of neuropeptide Y and its related peptides

Larhammar, Dan; Blomqvist, Anders; Söderberg, Charlotte

doi:10.1016/0742-8413(93)90236-e

Cited by 58 publications

(59 citation statements)

References 56 publications

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“…As the biomarker for obesity, NPY is a major mediator in promoting energy storage [104], which regulates food intake, fat deposition and metabolism via various G-proteincoupled NPY receptors including NPY receptor subtype 1, 2, and 5 [105,106]. For example, the NPY receptor sub-type 5 antagonist, Velneperit, has been identified in clinical tests as a potential anti-obesity drug [107,108].…”

Section: The Role Of Npy and Agrp In Sga-induced Weight Gainmentioning

confidence: 99%

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Lian

Huang

Pai

et al. 2016

Pharmacological Research

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Second generation antipsychotic drugs (SGAs) cause substantial body weight gain/obesity and other metabolic side-effects such as dyslipidaemia. Their antagonistic affinity to the histaminergic H1 receptor (H1R) has been identified as one of the main contributors to weight gain/obesity side-effects. The effects and mechanisms of betahistine (a histaminergic H1R agonist and H3 receptor antagonist) have been investigated for ameliorating SGA-induced weight gain/obesity in both animal models and clinical trials. It has been demonstrated that co-treatment with betahistine is effective in reducing weight gain, associated with olanzapine in drug-naïve patients with schizophrenia, as well as in the animal models of both drug-naïve rats and rats with chronic, repeated exposure to olanzapine. Betahistine co-treatment can reduce food intake and increase the effect of thermogenesis in brown adipose tissue by modulating hypothalamic H1R-NPY-AMPKα (NPY: neuropeptide Y; AMPKα: AMP-activated protein kinase α) pathways, and ameliorate olanzapineinduced dyslipidaemia through modulation of AMPKα-SREBP-1-PPARα-dependent pathways (SREBP-1: Sterol regulatory element binding protein 1; PPARα: Peroxisome proliferator-activated receptor-α) in the liver. Although reduced locomotor activity was observed from antipsychotic treatment in rats, betahistine did not affect locomotor activity. Importantly, betahistine co-treatment did not influence the effects of antipsychotics on serotonergic receptors in the key brain regions for antipsychotic therapeutic efficacy. However, betahistine co-treatment reverses the upregulated dopamine D2 binding caused by chronic olanzapine administration, which may be beneficial in reducing D2 supersensitivity often observed in chronic antipsychotic treatment. Therefore, these results provide solid evidence supporting further clinical trials in treating antipsychotics-induced weight gain using betahistine in patients with schizophrenia and other mental disorders.

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Section: The Role Of Npy and Agrp In Sga-induced Weight Gainmentioning

confidence: 99%

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Lian

Huang

Pai

et al. 2016

Pharmacological Research

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“…These and several other examples show that information about chromosomal localization is an important complement to sequence-based analyses to deduce gene relationships and species phylogenies. For example, NPY and PYY have arisen from a common ancestor through a chromosomal duplication, with the NPY gene (HSA7q15.1) close to the HOXA cluster (HSA7p15-p14), whereas PYY (HSA17q21.1) is close to the HOXB cluster (HSA17q21-q22) (Larhammar et al 1997). The third member, PP, arose through a local and more recent tandem duplication of PYY (Hort et al 1995;Larhammar 1996).…”

Section: Af227956 (For Pig Y6 Sequence)]mentioning

confidence: 99%

Evolution of the Neuropeptide Y Receptor Family: Gene and Chromosome Duplications Deduced from the Cloning and Mapping of the Five Receptor Subtype Genes in Pig

Wraith¹,

Törnsten²,

Chardon³

et al. 2000

Genome Res.

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Neuropeptide Y (NPY) receptors mediate a variety of physiological responses including feeding and vasoconstriction. To investigate the evolutionary events that have generated this receptor family, we have sequenced and determined the chromosomal localizations of all five presently known mammalian NPY receptor subtype genes in the domestic pig, Sus scrofa (SSC). The orthologs of the Y 1 and Y 2 subtypes display high amino acid sequence identities between pig, human, and mouse (92%-94%), whereas the Y 4 , Y 5 , and y 6 subtypes display lower identities (76%-87%). The lower identity of Y 5 is due to high sequence divergence in the large third intracellular loop. The NPY1R, NPY2R, and NPY5R receptor genes were localized to SSC8, the NPY4R to SSC14, and NPY6R to SSC2. Our comparisons strongly suggest that the tight cluster of NPY1R, NPY2R, and NPY5R on human chromosome 4 (HSA4) represents the ancestral configuration, whereas the porcine cluster has been split by two inversions on SSC8. These 3 genes, along with adjacent genes from 14 other gene families, form a cluster on HSA4 with extensive similarities to a cluster on HSA5, where NPY6R and >13 other paralogs reside, as well as another large cluster on HSA10 that includes NPY4R. Thus, these gene families have expanded through large-scale duplications. The sequence comparisons show that the NPY receptor triplet NPY1R-NPY2R-NPY5R existed before these large-scale duplications.

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“…The neuropeptide Y (NPY) gene family, which also includes peptide YY (PYY) and pancreatic polypeptide (PP), is an example of multiple gene duplication events giving rise to a range of structurally related but functionally distinct gene products (1). NPY is one of the most highly conserved peptides known (for example, with only three amino acid differences between human and shark NPY), suggesting that this peptide subserves evolutionary old and important functions.…”

Section: Introductionmentioning

confidence: 99%

Seminalplasmin: recent evolution of another member of the neuropeptide Y gene family.

Herzog

Hort

Schneider

et al. 1995

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

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Seminalplasmin, the major basic protein of bull semen, an important regulator of calcium transport in bovine sperm and a positive modulator of the zona pellucidainduced acrosome reaction, is shown to be a recently created member of the neuropeptide Y gene family. Sequence (PP), is an example of multiple gene duplication events giving rise to a range of structurally related but functionally distinct gene products (1). NPY is one of the most highly conserved peptides known (for example, with only three amino acid differences between human and shark NPY), suggesting that this peptide subserves evolutionary old and important functions. In the mammalian nervous system, NPY is one of the most abundant neuropeptides and acts both centrally and peripherally to regulate the cardiovascular system. It also modulates a wide range of other important physiological activities, including appetite, central endocrine secretion, anxiety, and reproduction (2, 3). On the other hand, PYY is secreted from endocrine cells in the lower small intestine, colon, and pancreas. It acts in an inhibitory nature on the gastrointestinal tract, including inhibition of gastric acid secretion, gastric emptying, pancreatic exocrine secretion, and gut motility (4). The third member of the NPY family, PP, is secreted by cells within the endocrine and exocrine pancreas and specifically.inhibits the secretion of enzymes and bicarbonate from the exocrine pancreas (5).Analysis of the structure and localization of the genes encoding NPY, PYY, and PP has suggested that these genes arose from an initial gene duplication event that generated the NPY and PYY genes, followed by a subsequent duplication of the PYY gene to create the PP gene. The human NPY gene has been mapped to chromosome 7, while the PYY and PP genes lie only 10 kb apart on chromosome 17q21.1 (6). Consistent with this evolution by gene duplication, all three genes share a common intron/exon structure, although the three introns of the NPY gene (in all species studied to date) are much larger than the corresponding introns in the PYY and PP genes. The overall nucleotide sequence similarity between the three members of the gene family is restricted to the coding regions and ranges from approximately 55% (NPY vs. PYY) to 38% (NPY vs. PP) and 30% (PYY vs. PP).Recently we determined the gene structure and amino acid sequence of the human PYY gene (6). In the course of this work we noted an unusually high similarity between the signal peptide of human PYY and the major basic protein of bull semen, bovine seminalplasmin. A detailed statistical analysis of similarities between these proteins along their entire length confirmed them as being significantly homologous, suggesting that seminalplasmin may be a member of the NPY family, possibly having evolved from PYY. As no protein equivalent to seminalplasmin has been identified in humans, we determined the sequences of the members of the bovine NPY family to clarify the evolutionary origin of seminalplasmin. § MATERIALS AND METHODSGenomic Lib...

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Evolution of neuropeptide Y and its related peptides

Cited by 58 publications

References 56 publications

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Ameliorating antipsychotic-induced weight gain by betahistine: Mechanisms and clinical implications

Evolution of the Neuropeptide Y Receptor Family: Gene and Chromosome Duplications Deduced from the Cloning and Mapping of the Five Receptor Subtype Genes in Pig

Seminalplasmin: recent evolution of another member of the neuropeptide Y gene family.

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