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Gene Review

Npy  -  neuropeptide Y

Mus musculus

Synonyms: 0710005A05Rik, Pro-neuropeptide Y
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Disease relevance of Npy


Psychiatry related information on Npy


High impact information on Npy


Chemical compound and disease context of Npy

  • The response of NPY-null mice to diet-induced obesity, chemically induced obesity (monosodium glutamate and gold thioglucose), and genetic-based obesity (lethal yellow agouti, Ay; uncoupling protein-diphtheria toxin transgenics, UCP-DT) were all normal [14].
  • Hyperphagia and weight gain after gold-thioglucose: relation to hypothalamic neuropeptide Y and proopiomelanocortin [15].
  • After administration of insulin at a dose (60 mU ip) sufficient to cause moderate hypoglycemia (plasma glucose levels, 40 +/- 3 and 37 +/- 2 mg/dl for Npy+/+ and Npy-/- mice, respectively; P = not significant), 4-h food intake was increased 2.5-fold in Npy+/+ mice relative to saline-injected controls [16].
  • Hyperphagic feeding in response to insulin-induced hypoglycemia was therefore markedly attenuated in mice lacking NPY, and a similar feeding deficit was detected in these animals after neuroglucopenia induced by 2-deoxyglucose (500 mg/kg ip) [16].
  • In the present study, the effects of endogenous and applied NPY were investigated in C57Bl/6 mice that had experienced pilocarpine-induced status epilepticus and subsequently developed a robust recurrent mossy fiber pathway [17].
  • Together these results suggest that endogenous NPY tonically inhibits insulin secretion from islets and a reduction of islet NPY may serve as one of the mechanisms to increase insulin secretion when islets compensate for insulin resistance associated with obesity [18].

Biological context of Npy


Anatomical context of Npy

  • Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus [23].
  • Using electrophysiological recordings, we found that ghrelin stimulated the activity of arcuate NPY neurons and mimicked the effect of NPY in the paraventricular nucleus of the hypothalamus (PVH) [24].
  • We found that in response to NPY, primary cultures of mouse adrenal chromaffin cells secreted catecholamine, and that this effect was abolished in cultures from NPY Y(1) receptor knockout mice (Y(1)-/-) [25].
  • We propose that NPY controls the release and synthesis of catecholamine from the adrenal medulla and consequently contributes to the sympathoadrenal tone [25].
  • Therefore, central nervous system melanocortin signaling appears to be suppressed more effectively by fasting than by uncontrolled diabetes, which provides a plausible explanation for differences in the feeding response to these two stimuli in mice lacking NPY [5].

Associations of Npy with chemical compounds

  • To investigate NPY's role in the hyperphagic response to uncontrolled diabetes, streptozotocin (STZ) (200 mg/kg intraperitoneally) or saline vehicle was given to NPY-deficient (Npy(--/--)) and wild-type (Npy(+/+)) mice [5].
  • The molecular interaction between the Y(1) receptor and TH was demonstrated by the fact that NPY markedly inhibited the forskolin-induced luciferin activity in Y(1) receptor-expressing SK-N-MC cells transfected with a TH promoter sequence [25].
  • Fat pad weight as well as plasma insulin, leptin, and corticosterone levels were strongly increased in NPY-treated mice [26].
  • Neonatal lesioning of the hypothalamic arcuate nuclei (ARC) with monosodium glutamate markedly reduced the number of NPY fibers in the preoptic area as well as the frequency of their contacts with perikarya and proximal dendrites of GnRH neurons [27].
  • Origin of neuropeptide Y-containing afferents to gonadotropin-releasing hormone neurons in male mice [27].

Physical interactions of Npy


Co-localisations of Npy


Regulatory relationships of Npy

  • Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression [26].
  • These observations, in light of previous reports showing both NPY and CRH can inhibit GHRH expression and GH release, suggest that these neuronal systems may work in concert to control the ultimate impact of fasting on GH axis function [32].
  • Leptin rapidly inhibits hypothalamic neuropeptide Y secretion and stimulates corticotropin-releasing hormone secretion in adrenalectomized mice [33].
  • These studies demonstrate that hypothalamic AgRP mRNA and immunoreactivity are upregulated with fasting and that these increases are not affected by NPY deficiency [6].
  • Thus MC4R deficiency augments age-induced NPY expression in the DMN and VMN with no feedback from body fat content [34].

Other interactions of Npy

  • Like its effect in lean mice, C75 prevented the fasting-induced increase of hypothalamic NPY and AgRP mRNAs in obese mice, but had no effect on the expression of POMC and CART mRNAs [20].
  • Finally, the induced suppression of food intake and leptin levels occurred despite unchanged or increased hypothalamic expression of the orexigenic neuropeptides NPY and MCH [35].
  • Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic nucleus in two models of the agouti obesity syndrome [36].
  • To test this hypothesis, we examined if AGRP mRNA would be, like NPY mRNA, inhibited by leptin injections and stimulated by fasting [37].
  • The present study examined whether elevated NPY mRNA and/or decreased POMC mRNA in the hypothalamus are associated with obesity due to hypothalamic lesions [15].

Analytical, diagnostic and therapeutic context of Npy

  • To test this hypothesis we evaluated mRNA expression of Npy, Agrp, and Pomc by in situ hybridization in the hypothalamic arcuate nucleus (ARC) of 3-day-old female and male PWS neonates [38].
  • Fasting in lean rats (+/fa) for 72 h significantly increased Agrp and Npy mRNA expression, and decreased Pomc mRNA expression as detected by a sensitive solution hybridization/S1 nuclease protection assay [23].
  • The decrement in dwarf mice of total ARC NPY mRNA without reduction in mRNA per cell suggested a reduction in NPY-containing neuron number, which was the case as shown by immunocytochemistry [39].
  • We confirmed that the decrease in NPY expression previously detected by Northern blots reflects a decrease in NPY expression in the arcuate nucleus [40].
  • Dual-label immunofluorescence studies to determine the precise contribution of the ARC to the innervation of GnRH neurons by NPY axons were carried out on transgenic mice in which enhanced green fluorescent protein was expressed under the control of the GnRH promoter (GnRH-enhanced green fluorescent protein mice) [27].


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  12. Gut hormone PYY(3-36) physiologically inhibits food intake. Batterham, R.L., Cowley, M.A., Small, C.J., Herzog, H., Cohen, M.A., Dakin, C.L., Wren, A.M., Brynes, A.E., Low, M.J., Ghatei, M.A., Cone, R.D., Bloom, S.R. Nature (2002) [Pubmed]
  13. Leptin-regulated endocannabinoids are involved in maintaining food intake. Di Marzo, V., Goparaju, S.K., Wang, L., Liu, J., Bátkai, S., Járai, Z., Fezza, F., Miura, G.I., Palmiter, R.D., Sugiura, T., Kunos, G. Nature (2001) [Pubmed]
  14. Life without neuropeptide Y. Palmiter, R.D., Erickson, J.C., Hollopeter, G., Baraban, S.C., Schwartz, M.W. Recent Prog. Horm. Res. (1998) [Pubmed]
  15. Hyperphagia and weight gain after gold-thioglucose: relation to hypothalamic neuropeptide Y and proopiomelanocortin. Bergen, H.T., Mizuno, T.M., Taylor, J., Mobbs, C.V. Endocrinology (1998) [Pubmed]
  16. Neuropeptide Y is required for hyperphagic feeding in response to neuroglucopenia. Sindelar, D.K., Ste Marie, L., Miura, G.I., Palmiter, R.D., McMinn, J.E., Morton, G.J., Schwartz, M.W. Endocrinology (2004) [Pubmed]
  17. Neuropeptide Y regulates recurrent mossy fiber synaptic transmission less effectively in mice than in rats: Correlation with Y2 receptor plasticity. Tu, B., Jiao, Y., Herzog, H., Nadler, J.V. Neuroscience (2006) [Pubmed]
  18. Insulin secretion is increased in pancreatic islets of neuropeptide Y-deficient mice. Imai, Y., Patel, H.R., Hawkins, E.J., Doliba, N.M., Matschinsky, F.M., Ahima, R.S. Endocrinology (2007) [Pubmed]
  19. A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice. Ishihara, A., Kanatani, A., Mashiko, S., Tanaka, T., Hidaka, M., Gomori, A., Iwaasa, H., Murai, N., Egashira, S., Murai, T., Mitobe, Y., Matsushita, H., Okamoto, O., Sato, N., Jitsuoka, M., Fukuroda, T., Ohe, T., Guan, X., Macneil, D.J., Van der Ploeg, L.H., Nishikibe, M., Ishii, Y., Ihara, M., Fukami, T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  20. Effect of a fatty acid synthase inhibitor on food intake and expression of hypothalamic neuropeptides. Shimokawa, T., Kumar, M.V., Lane, M.D. Proc. Natl. Acad. Sci. U.S.A. (2002) [Pubmed]
  21. Obesity and endocrine dysfunction in mice with deletions of both neuropeptide Y and galanin. Hohmann, J.G., Teklemichael, D.N., Weinshenker, D., Wynick, D., Clifton, D.K., Steiner, R.A. Mol. Cell. Biol. (2004) [Pubmed]
  22. 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. Wraith, A., Törnsten, A., Chardon, P., Harbitz, I., Chowdhary, B.P., Andersson, L., Lundin, L.G., Larhammar, D. Genome Res. (2000) [Pubmed]
  23. Leptin regulation of Agrp and Npy mRNA in the rat hypothalamus. Korner, J., Savontaus, E., Chua, S.C., Leibel, R.L., Wardlaw, S.L. J. Neuroendocrinol. (2001) [Pubmed]
  24. The distribution and mechanism of action of ghrelin in the CNS demonstrates a novel hypothalamic circuit regulating energy homeostasis. Cowley, M.A., Smith, R.G., Diano, S., Tschöp, M., Pronchuk, N., Grove, K.L., Strasburger, C.J., Bidlingmaier, M., Esterman, M., Heiman, M.L., Garcia-Segura, L.M., Nillni, E.A., Mendez, P., Low, M.J., Sotonyi, P., Friedman, J.M., Liu, H., Pinto, S., Colmers, W.F., Cone, R.D., Horvath, T.L. Neuron (2003) [Pubmed]
  25. Deletion of the neuropeptide Y (NPY) Y1 receptor gene reveals a regulatory role of NPY on catecholamine synthesis and secretion. Cavadas, C., Céfai, D., Rosmaninho-Salgado, J., Vieira-Coelho, M.A., Moura, E., Busso, N., Pedrazzini, T., Grand, D., Rotman, S., Waeber, B., Aubert, J.F., Grouzmann, E. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  26. Chronic neuropeptide Y infusion into the lateral ventricle induces sustained feeding and obesity in mice lacking either Npy1r or Npy5r expression. Raposinho, P.D., Pedrazzini, T., White, R.B., Palmiter, R.D., Aubert, M.L. Endocrinology (2004) [Pubmed]
  27. Origin of neuropeptide Y-containing afferents to gonadotropin-releasing hormone neurons in male mice. Turi, G.F., Liposits, Z., Moenter, S.M., Fekete, C., Hrabovszky, E. Endocrinology (2003) [Pubmed]
  28. Marked decrease of neuropeptide Y Y2 receptor binding sites in the hippocampus in murine prion disease. Diez, M., Koistinaho, J., Dearmond, S.J., Groth, D., Prusiner, S.B., Hökfelt, T. Proc. Natl. Acad. Sci. U.S.A. (1997) [Pubmed]
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  31. Activation of proteinase-activated receptor-1 inhibits neurally evoked chloride secretion in the mouse colon in vitro. Buresi, M.C., Vergnolle, N., Sharkey, K.A., Keenan, C.M., Andrade-Gordon, P., Cirino, G., Cirillo, D., Hollenberg, M.D., MacNaughton, W.K. Am. J. Physiol. Gastrointest. Liver Physiol. (2005) [Pubmed]
  32. Severity of the catabolic condition differentially modulates hypothalamic expression of growth hormone-releasing hormone in the fasted mouse: potential role of neuropeptide y and corticotropin-releasing hormone. Luque, R.M., Park, S., Kineman, R.D. Endocrinology (2007) [Pubmed]
  33. Leptin rapidly inhibits hypothalamic neuropeptide Y secretion and stimulates corticotropin-releasing hormone secretion in adrenalectomized mice. Jang, M., Mistry, A., Swick, A.G., Romsos, D.R. J. Nutr. (2000) [Pubmed]
  34. Age-dependent hypothalamic expression of neuropeptides in wild-type and melanocortin-4 receptor-deficient mice. Arens, J., Moar, K.M., Eiden, S., Weide, K., Schmidt, I., Mercer, J.G., Simon, E., Korf, H.W. Physiol. Genomics (2003) [Pubmed]
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  36. Induction of neuropeptide Y gene expression in the dorsal medial hypothalamic nucleus in two models of the agouti obesity syndrome. Kesterson, R.A., Huszar, D., Lynch, C.A., Simerly, R.B., Cone, R.D. Mol. Endocrinol. (1997) [Pubmed]
  37. Hypothalamic agouti-related protein messenger ribonucleic acid is inhibited by leptin and stimulated by fasting. Mizuno, T.M., Mobbs, C.V. Endocrinology (1999) [Pubmed]
  38. Anorexigenic melanocortin signaling in the hypothalamus is augmented in association with failure-to-thrive in a transgenic mouse model for Prader-Willi syndrome. Ge, Y., Ohta, T., Driscoll, D.J., Nicholls, R.D., Kalra, S.P. Brain Res. (2002) [Pubmed]
  39. Reduced hypothalamic neuropeptide Y expression in growth hormone- and prolactin-deficient Ames and Snell dwarf mice. Hurley, D.L., Birch, D.V., Almond, M.C., Estrada, I.J., Phelps, C.J. Endocrinology (2003) [Pubmed]
  40. Characterization of expression of hypothalamic appetite-regulating peptides in obese hyperleptinemic brown adipose tissue-deficient (uncoupling protein-promoter-driven diphtheria toxin A) mice. Tritos, N.A., Elmquist, J.K., Mastaitis, J.W., Flier, J.S., Maratos-Flier, E. Endocrinology (1998) [Pubmed]
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