Neuroendocrinology

Neuroendocrine Control of Feeding Behaviour

Peptide YY Directly Inhibits Ghrelin-Activated Neurons of the Arcuate Nucleus and Reverses Fasting-Induced c-Fos Expression

Riediger T. · Bothe C. · Becskei C. · Lutz T.A.

Author affiliations

Institute of Veterinary Physiology, University of Zurich, Zurich, Switzerland

Keywords: ElectrophysiologyImmunohistochemistryFood intakeEnergy balanceGhrelinBrainstemc-FosArcuate nucleusPeptide YYArea postremaMiceNeurosteroids

Related Articles for ""
Neuroendocrinology 2004;79:317–326
https://doi.org/10.1159/000079842

Log in to MyKarger to check if you already have access to this content.




Forgot your password
Sign up to MyKarger

Buy

  • FullText & PDF
  • Unlimited re-access via MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more
CHF 38.00 *
EUR 35.00 *
USD 39.00 *

Select

KAB

Buy a Karger Article Bundle (KAB) and profit from a discount!


If you would like to redeem your KAB credit, please log in.

Save over 20% compared to the individual article price.

Learn more

Rent/Cloud

  • Rent for 48h to view
  • Buy Cloud Access for unlimited viewing via different devices
  • Synchronizing in the ReadCube Cloud
  • Printing and saving restrictions apply
Rental: USD 8.50
Cloud: USD 20.00

Select

Subscribe

  • Access to all articles of the subscribed year(s) guaranteed for 5 years
  • Unlimited re-access via Subscriber Login or MyKarger
  • Unrestricted printing, no saving restrictions for personal use
read more

Subcription rates

Select
* The final prices may differ from the prices shown due to specifics of VAT rules.

Article / Publication Details

First-Page Preview
Abstract of Neuroendocrine Control of Feeding Behaviour

Published online: August 20, 2004
Issue release date: November 2004

Number of Print Pages: 10
Number of Figures: 7
Number of Tables: 2

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Abstract

The hypothalamic arcuate nucleus (Arc) monitors and integrates hormonal and metabolic signals involved in the maintenance of energy homeostasis. The orexigenic peptide ghrelin is secreted from the stomach during negative status of energy intake and directly activates neurons of the medial arcuate nucleus (ArcM) in rats. In contrast to ghrelin, peptide YY (PYY) is released postprandially from the gut and reduces food intake when applied peripherally. Neurons in the ArcM express ghrelin receptors and neuropeptide Y receptors. Thus, PYY may inhibit feeding by acting on ghrelin-sensitive Arc neurons. Using extracellular recordings, we (1) characterized the effects of PYY on the electrical activity of ghrelin-sensitive neurons in the ArcM of rats. In order to correlate the effect of PYY on neuronal activity with the energy status, we (2) investigated the ability of PYY to reverse fasting-induced c-Fos expression in Arc neurons of mice. In addition, we (3) sought to confirm that PYY reduces food intake under our experimental conditions. Superfusion of PYY reversibly inhibited 94% of all ArcM neurons by a direct postsynaptic mechanism. The PYY-induced inhibition was dose-dependent and occurred at a threshold concentration of 10–8M. Consistent with the opposite effects of ghrelin and PYY on food intake, a high percentage (50%) of Arc neurons was activated by ghrelin and inhibited by PYY. In line with this inhibitory action, peripherally injected PYY partly reversed the fasting-induced c-Fos expression in Arc neurons of mice. Similarly, refeeding of food-deprived mice reversed the fasting-induced activation in the Arc. Furthermore, peripherally injected PYY reduced food intake in 12-hour fasted mice. Thus the activity of Arc neurons correlated with the feeding status and was not only reduced by feeding but also by administration of PYY in non-refed mice. In conclusion, our current observations suggest that PYY may contribute to signaling a positive status of energy intake by inhibiting Arc neurons, which are activated under a negative status of energy intake by signals such as ghrelin.

© 2004 S. Karger AG, Basel



Related Articles:

References

  1. Tatemoto K: Isolation and characterization of peptide YY, a candidate gut hormone that inhibits pancreatic exocrine secretion. Proc Natl Acad Sci USA 1982;79:2514–2518.
    External Resources
  2. Ali-Rachedi A, Varndell IM, Adrian TE, Gapp DA, Van Noorden S, Bloom SR, Polak JM: Peptide YY immunoreactivity is co-stored with glucagon-related immunoreactants in endocrine cells of the gut and pancreas. Histochemistry 1984;80:487–491.
    External Resources
  3. El Salhy M, Wilander E, Juntti-Berggren L, Grimelius L: The distribution and ontogeny of polypeptide YY- and pancreatic polypeptide-immunoreactive cells in the gastrointestinal tract of rat. Histochemistry 1983;78:53–60.
    External Resources
  4. Rudnicki M, McFadden DW, Liwnicz BH, Balasubramaniam A, Nussbaum MS, Dayal R, Fischer JE: Endogenous peptide YY is dependent on jejunal exposure to gastrointestinal contents. J Surg Res 1990;48:485–490.
    External Resources
  5. Greeley GH Jr, Jeng YJ, Gomez G, Hashimoto T, Hill FL, Kern K, Kurosky T, Chuo HF, Thompson JC: Evidence for regulation of peptide-YY release by the proximal gut. Endocrinology 1989;124:1438–1443.
    External Resources
  6. Greeley GH Jr, Hashimoto T, Izukura M, Gomez G, Jeng J, Hill FL, Lluis F, Thompson JC: A comparison of intraduodenally and intracolonically administered nutrients on the release of peptide-YY in the dog. Endocrinology 1989;125:1761–1765.
    External Resources
  7. Grandt D, Schimiczek M, Beglinger C, Layer P, Goebell H, Eysselein VE, Reeve JR Jr: Two molecular forms of peptide YY (PYY) are abundant in human blood: Characterization of a radioimmunoassay recognizing PYY 1–36 and PYY 3–36. Regul Pept 1994;51:151–159.
    External Resources
  8. Adrian TE, Savage AP, Sagor GR, Allen JM, Bacarese-Hamilton AJ, Tatemoto K, Polak JM, Bloom SR: Effect of peptide YY on gastric, pancreatic, and biliary function in humans. Gastroenterology 1985;89:494–499.
    External Resources
  9. Allen JM, Fitzpatrick ML, Yeats JC, Darcy K, Adrian TE, Bloom SR: Effects of peptide YY and neuropeptide Y on gastric emptying in man. Digestion 1984;30:255–262.
    External Resources
  10. Pappas TN, Debas HT, Goto Y, Taylor IL: Peptide YY inhibits meal-stimulated pancreatic and gastric secretion. Am J Physiol 1985;248:G118–G123.
  11. Savage AP, Adrian TE, Carolan G, Chatterjee VK, Bloom SR: Effects of peptide YY (PYY) on mouth to caecum intestinal transit time and on the rate of gastric emptying in healthy volunteers. Gut 1987;28:166–170.
    External Resources
  12. Al Saffar A, Hellstrom PM, Nylander G: Correlation between peptide YY-induced myoelectric activity and transit of small-intestinal contents in rats. Scand J Gastroenterol 1985;20:577–582.
    External Resources
  13. Morley JE, Levine AS, Grace M, Kneip J: Peptide YY, a potent orexigenic agent. Brain Res 1985;341:200–203.
    External Resources
  14. Clark JT, Sahu A, Kalra PS, Balasubramaniam A, Kalra SP: Neuropeptide Y (NPY)-induced feeding behavior in female rats: Comparison with human NPY ([Met17]NPY), NPY analog ([norLeu4]NPY) and peptide YY. Regul Pept 1987;17:31–39.
    External Resources
  15. Corp ES, Melville LD, Greenberg D, Gibbs J, Smith GP: Effect of fourth ventricular neuropeptide Y and peptide YY on ingestive and other behaviors. Am J Physiol 1990;259:R317–R323.
  16. Stanley BG, Daniel DR, Chin AS, Leibowitz SF: Paraventricular nucleus injections of peptide YY and neuropeptide Y preferentially enhance carbohydrate ingestion. Peptides 1985;6:1205–1211.
    External Resources
  17. Batterham RL, Cowley MA, Small CJ, Herzog H, Cohen MA, Dakin CL, Wren AM, Brynes AE, Low MJ, Ghatei MA, Cone RD, Bloom SR: Gut hormone PYY(3–36) physiologically inhibits food intake. Nature 2002;418:650–654.
    External Resources
  18. Keire DA, Mannon P, Kobayashi M, Walsh JH, Solomon TE, Reeve JR, Jr: Primary structures of PYY, [Pro(34)]PYY, and PYY-(3–36) confer different conformations and receptor selectivity. Am J Physiol 2000;279:G126–G131.
  19. Woods SC, Seeley RJ, Porte D Jr, Schwartz MW: Signals that regulate food intake and energy homeostasis. Science 1998;280:1378–1383.
    External Resources
  20. Broberger C, Landry M, Wong H, Walsh JN, Hokfelt T: Subtypes Y1 and Y2 of the neuropeptide Y receptor are respectively expressed in pro-opiomelanocortin- and neuropeptide-Y-containing neurons of the rat hypothalamic arcuate nucleus. Neuroendocrinology 1997;66:393–408.
    External Resources
  21. Kojima M, Hosoda H, Date Y, Nakazato M, Matsuo H, Kangawa K: Ghrelin is a growth-hormone-releasing acylated peptide from stomach. Nature 1999;402:656–660.
    External Resources
  22. Tschop M, Smiley DL, Heiman ML: Ghrelin induces adiposity in rodents. Nature 2000;407:908–913.
    External Resources
  23. Guan XM, Yu H, Palyha OC, McKee KK, Feighner SD, Sirinathsinghji DJ, Smith RG, Van der Ploeg LH, Howard AD: Distribution of mRNA encoding the growth hormone secretagogue receptor in brain and peripheral tissues. Brain Res 1997;48:23–29.
    External Resources
  24. Tannenbaum GS, Lapointe M, Beaudet A, Howard AD: Expression of growth hormone secretagogue receptors by growth hormone-releasing hormone neurons in the mediobasal hypothalamus. Endocrinology 1998;139:4420–4423.
    External Resources
  25. Nakazato M, Murakami N, Date Y, Kojima M, Matsuo H, Kangawa K, Matsukura S: A role for ghrelin in the central regulation of feeding. Nature 2001;409:194–198.
    External Resources
  26. Wren AM, Small CJ, Ward HL, Murphy KG, Dakin CL, Taheri S, Kennedy AR, Roberts GH, Morgan DG, Ghatei MA, Bloom SR: The novel hypothalamic peptide ghrelin stimulates food intake and growth hormone secretion. Endocrinology 2000;141:4325–4328.
    External Resources
  27. Traebert M, Riediger T, Whitebread S, Scharrer E, Schmid HA: Ghrelin acts on leptin-responsive neurones in the rat arcuate nucleus. J Neuroendocrinol 2002;14:580–586.
    External Resources
  28. Riediger T, Traebert M, Schmid HA, Scheel C, Lutz TA, Scharrer E: Site-specific effects of ghrelin on the neuronal activity in the hypothalamic arcuate nucleus. Neurosci Lett 2003;341:151–155.
    External Resources
  29. Tung YC, Hewson AK, Dickson SL: Actions of leptin on growth hormone secretagogue-responsive neurones in the rat hypothalamic arcuate nucleus recorded in vitro. J Neuroendocrinol 2001;13:209–215.
    External Resources
  30. Hewson AK, Viltart O, McKenzie DN, Dyball RE, Dickson SL: GHRP-6-induced changes in electrical activity of single cells in the arcuate, ventromedial and periventricular nucleus neurones of a hypothalamic slice preparation in vitro. J Neuroendocrinol 1999;11:919–923.
    External Resources
  31. Lutz TA, Senn M, Althaus J, Del Prete E, Ehrensperger F, Scharrer E: Lesion of the area postrema/nucleus of the solitary tract attenuates the anorectic effects of amylin and calcitonin gene-related peptide in rats. Peptides 1998;19:309–317.
    External Resources
  32. Riediger T, Schmid HA, Lutz T, Simon E: Amylin potently activates AP neurons possibly via formation of the excitatory second messenger cGMP. Am J Physiol 2001;281:R1833–R1843.
  33. Riediger T, Zuend D, Becskei C, Lutz TA: The anorectic hormone amylin contributes to feeding-related changes of neuronal activity in key structures of the gut-brain axis. Am J Physiol 2004;286:R114–R122.
  34. Bonaz B, Taylor I, Tache Y: Peripheral peptide YY induces c-fos-like immunoreactivity in the rat brain. Neurosci Lett 1993;163:77–80.
    External Resources
  35. Paxinos G, Watson C: The Rat Brain in Stereotaxic Coordinates, ed 4. New York, Academic Press, 1998.
  36. Kelso SR, Boulant JA: Effect of synaptic blockade on thermosensitive neurons in hypothalamic tissue slices. Am J Physiol 1982;243:R480–R490.
    External Resources
  37. Hof PR, Young WG, Bloom FE, Belichenko PV, Celio MRE: Comparative cytoarchitectonic atlas of the C57BL/6 and 129/Sv mouse brains. Amsterdam, Elsevier, 2000.
  38. Rauch M, Riediger T, Schmid HA, Simon E: Orexin A activates leptin-responsive neurons in the arcuate nucleus. Pflügers Arch 2000;440:699–703.
  39. Belousov AB, van den Pol AN: Local synaptic release of glutamate from neurons in the rat hypothalamic arcuate nucleus. J Physiol 1997;499:747–761.
    External Resources
  40. Anini Y, Fu-Cheng X, Cuber JC, Kervran A, Chariot J, Roz C: Comparison of the postprandial release of peptide YY and proglucagon-derived peptides in the rat. Pflügers Arch 1999;438:299–306.
  41. Soffer EE, Adrian TE, Launspach J, Zimmerman B: Meal-induced secretion of gastrointestinal regulatory peptides is not affected by sleep. Neurogastroenterol Motil 1997;9:7–12.
    External Resources
  42. Larsen PJ, Tang-Christensen M, Holst JJ, Orskov C: Distribution of glucagon-like peptide-1 and other preproglucagon-derived peptides in the rat hypothalamus and brainstem. Neuroscience 1997;77:257–270.
    External Resources
  43. Vrang N, Phifer CB, Corkern MM, Berthoud HR: Gastric distension induces c-Fos in medullary GLP-1/2-containing neurons. Am J Physiol 2003;285:R470–R478.
  44. Neary NN, Small CJ, Park AJ, Ellis SM, Filipsson K, Wang F, Dakin CL, Ghatei MA, Bloom SR: Gut hormones peptide YY3–36 and glucagon like peptide-1 have an additive physiological role in the inhibition of food intake. Soc Neurosci Abstr 2003;33:abstr 231.1.
  45. Keire DA, Bowers CW, Solomon TE, Reeve JR Jr: Structure and receptor binding of PYY analogs. Peptides 2002;23:305–321.
    External Resources
  46. Wang L, Martinez V, Barrachina MD, Tache Y: Fos expression in the brain induced by peripheral injection of CCK or leptin plus CCK in fasted lean mice. Brain Res 1998;791:157–166.
    External Resources
  47. Mistry AM, Helferich W, Romsos DR: Elevated neuronal c-Fos-like immunoreactivity and messenger ribonucleic acid in genetically obese (ob/ob) mice. Brain Res 1994;666:53–60.
    External Resources
  48. Morikawa Y, Ueyama E, Senba E: Fasting-induced activation of mitogen-activated protein kinases (ERK/p38) in the mouse hypothalamus. J Neuroendocrinol 2004;16:105–112.
    External Resources
  49. Ishii S, Kamegai J, Tamura H, Shimizu T, Sugihara H, Oikawa S: Hypothalamic neuropeptide Y/Y1 receptor pathway activated by a reduction in circulating leptin, but not by an increase in circulating ghrelin, contributes to hyperphagia associated with triiodothyronine-induced thyrotoxicosis. Neuroendocrinology 2003;78:321–330.
    External Resources
  50. Merchenthaler I: Neurons with access to the general circulation in the central nervous system of the rat: A retrograde tracing study with fluoro-gold. Neuroscience 1991;44:655–662.
    External Resources
  51. Nonaka N, Shioda S, Niehoff ML, Banks WA: Characterization of blood-brain barrier permeability to PYY3–36 in the mouse. J Pharmacol Exp Ther 2003;306:948–953.
    External Resources
  52. Chen CH, Rogers RC: Peptide YY and the Y2 agonist PYY(13–36) inhibit neurons of the dorsal motor nucleus of the vagus. Am J Physiol 1997;273:R213-lR218.
  53. Chen CH, Stephens RL Jr, Rogers RC: PYY and NPY: Control of gastric motility via action on Y1 and Y2 receptors in the DVC. Neurogastroenterol Motil 1997;9:109–116.
    External Resources
  54. Yang H, Tache Y: PYY in brain stem nuclei induces vagal stimulation of gastric acid secretion in rats. Am J Physiol 1995;268:G943–G948.
  55. Hernandez EJ, Whitcomb DC, Vigna SR, Taylor IL: Saturable binding of circulating peptide YY in the dorsal vagal complex of rats. Am J Physiol 1994;266:G511–G516.
  56. Leslie RA, McDonald TJ, Robertson HA: Autoradiographic localization of peptide YY and neuropeptide Y binding sites in the medulla oblongata. Peptides 1988;9:1071–1076.
    External Resources

Article / Publication Details

First-Page Preview
Abstract of Neuroendocrine Control of Feeding Behaviour

Published online: August 20, 2004
Issue release date: November 2004

Number of Print Pages: 10
Number of Figures: 7
Number of Tables: 2

ISSN: 0028-3835 (Print)
eISSN: 1423-0194 (Online)

For additional information: https://www.karger.com/NEN

Copyright / Drug Dosage / Disclaimer

Copyright: All rights reserved. No part of this publication may be translated into other languages, reproduced or utilized in any form or by any means, electronic or mechanical, including photocopying, recording, microcopying, or by any information storage and retrieval system, without permission in writing from the publisher.
Drug Dosage: The authors and the publisher have exerted every effort to ensure that drug selection and dosage set forth in this text are in accord with current recommendations and practice at the time of publication. However, in view of ongoing research, changes in government regulations, and the constant flow of information relating to drug therapy and drug reactions, the reader is urged to check the package insert for each drug for any changes in indications and dosage and for added warnings and precautions. This is particularly important when the recommended agent is a new and/or infrequently employed drug.
Disclaimer: The statements, opinions and data contained in this publication are solely those of the individual authors and contributors and not of the publishers and the editor(s). The appearance of advertisements or/and product references in the publication is not a warranty, endorsement, or approval of the products or services advertised or of their effectiveness, quality or safety. The publisher and the editor(s) disclaim responsibility for any injury to persons or property resulting from any ideas, methods, instructions or products referred to in the content or advertisements.

Article Tools
Article Details

2004, Vol.79, No. 6

November 2004

Article

Recommend This
TOP