Digestive Diseases and Sciences

, Volume 60, Issue 6, pp 1595–1602 | Cite as

Nesfatin-1 Suppresses Gastric Contractions and Inhibits Interdigestive Migrating Contractions in Conscious Dogs

  • Akira WatanabeEmail author
  • Erito Mochiki
  • Akiharu Kimura
  • Norimichi Kogure
  • Mitsuhiro Yanai
  • Atsushi Ogawa
  • Yoshitaka Toyomasu
  • Kyoichi Ogata
  • Tetsuro Ohno
  • Hideki Suzuki
  • Hiroyuki Kuwano
Original Article



Nesfatin-1 is a novel 82-amino acid anorectic peptide. Acute injection of nesfatin-1 into the third brain ventricle reduces food consumption during the dark phase in rats. Nesfatin-1 is also expressed in gastric X/A-like cells in the peripheral tissues. Nesfatin-1 has been reported to reduce gastric and duodenal motility and to delay gastric emptying.


In the present study, we investigated the effects of nesfatin-1 on gastrointestinal motility in conscious dogs.


Force transducers were implanted onto the serosal surfaces of the gastric bodies, gastric antra, duodena, and jejuna of healthy beagle dogs, and gastrointestinal motility was monitored. We evaluated the effects of nesfatin-1 on gastrointestinal motility and on the circulating levels of nesfatin-1 in the fasted and fed states.


The intravenous administration of nesfatin-1 reduced gastric contractions and inhibited cyclical interdigestive migrating contractions in the fasted state. In the fasted state, circulating levels of nesfatin-1 tended to increase during late phase I. In addition, the kinetics of the circulating levels of nesfatin-1 were opposite to those of ghrelin during the fasted state.


Nesfatin-1 regulates gastrointestinal motility, and, in particular, it inhibits gastric contractions in the fasted state. Interdigestive migrating contractions may be regulated by interactions between nesfatin-1, ghrelin, and motilin.


Nesfatin-1 Ghrelin Motilin Gastrointestinal motility Interdigestive migrating contractions 



Interdigestive migrating contractions


Motility index





We thank Ms. Yukie Saito, Ms. Tomoko Yano, Ms. Tomoko Ubukata, Ms. Yuka Matsui, Ms. Ayaka Ishida, and Ayaka Ishikubo for their excellent assistance.

Conflict of interest



  1. 1.
    Oh IS, Shimizu H, Satoh T, et al. Identification of nesfatin-1 as a satiety molecule in the hypothalamus. Nature. 2006;443:709–712. (Epub 10/13/2006).CrossRefGoogle Scholar
  2. 2.
    Stengel A, Goebel M, Wang L, et al. Central nesfatin-1 reduces dark-phase food intake and gastric emptying in rats: differential role of corticotropin-releasing factor2 receptor. Endocrinology. 2009;150:4911–4919. (Epub 10/03/2009).CrossRefPubMedCentralPubMedGoogle Scholar
  3. 3.
    Stengel A, Goebel M, Yakubov I, et al. Identification and characterization of nesfatin-1 immunoreactivity in endocrine cell types of the rat gastric oxyntic mucosa. Endocrinology. 2009;150:232–238. (Epub 09/27/2008).CrossRefPubMedCentralPubMedGoogle Scholar
  4. 4.
    Shimizu H, Oh IS, Hashimoto K, et al. Peripheral administration of nesfatin-1 reduces food intake in mice: the leptin-independent mechanism. Endocrinology. 2009;150:662–671. (Epub 01/30/2009).CrossRefPubMedGoogle Scholar
  5. 5.
    Zhang W, Zhang C, Fritze D, Chai B, Li J, Mulholland MW. Modulation of food intake by mTOR signalling in the dorsal motor nucleus of the vagus in male rats: focus on ghrelin and nesfatin-1. Exp Physiol. 2013;98:1696–1704. (Epub 08/21/2013).CrossRefPubMedGoogle Scholar
  6. 6.
    Bonnet MS, Ouelaa W, Tillement V, et al. Gastric distension activates NUCB2/nesfatin-1-expressing neurons in the nucleus of the solitary tract. Regul Pept. 2013;187:17–23. (Epub 10/15/2013).CrossRefPubMedGoogle Scholar
  7. 7.
    Pan W, Hsuchou H, Kastin AJ. Nesfatin-1 crosses the blood–brain barrier without saturation. Peptides. 2007;28:2223–2228. (Epub 10/24/2007).CrossRefPubMedGoogle Scholar
  8. 8.
    Price TO, Samson WK, Niehoff ML, Banks WA. Permeability of the blood–brain barrier to a novel satiety molecule nesfatin-1. Peptides. 2007;28:2372–2381. (Epub 11/17/2007).CrossRefPubMedGoogle Scholar
  9. 9.
    Cuomo R, Sarnelli G. Food intake and gastrointestinal motility. A complex interplay. Nutr Metab Cardiovasc Dis (NMCD). 2004;14:173–179. (Epub 11/24/2004).CrossRefGoogle Scholar
  10. 10.
    Cuomo R, D’Alessandro A, Andreozzi P, Vozzella L, Sarnelli G. Gastrointestinal regulation of food intake: do gut motility, enteric nerves and entero-hormones play together? Minerva Endocrinol. 2011;36:281–293. (Epub 02/11/2012).PubMedGoogle Scholar
  11. 11.
    Atsuchi K, Asakawa A, Ushikai M, et al. Centrally administered nesfatin-1 inhibits feeding behaviour and gastroduodenal motility in mice. NeuroReport. 2010;21:1008–1011. (Epub 09/10/2010).PubMedGoogle Scholar
  12. 12.
    Li ZL, Xu L, Sun XR, Guo FF, Gong YL, Gao SL. Central nesfatin-1 influences the excitability of ghrelin-responsive gastric distension neurons in the arcuate nucleus and reduces gastric motility in rats. Eur J Neurosci. 2013;38:3636–3643. (Epub 12/03/2013).CrossRefPubMedGoogle Scholar
  13. 13.
    Kamiyama Y, Aihara R, Nakabayashi T, Mochiki E, Asao T, Kuwano H. The peptide hormone xenin induces gallbladder contractions in conscious dogs. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2007;19:233–240. (Epub 02/16/2007).CrossRefGoogle Scholar
  14. 14.
    Ohno T, Kamiyama Y, Aihara R, et al. Ghrelin does not stimulate gastrointestinal motility and gastric emptying: an experimental study of conscious dogs. Neurogastroenterol Motil Off J Eur Gastrointest Motil Soc. 2006;18:129–135. (Epub 01/20/2006).CrossRefGoogle Scholar
  15. 15.
    Ogawa A, Mochiki E, Yanai M, et al. Interdigestive migrating contractions are coregulated by ghrelin and motilin in conscious dogs. Am J Physiol Regul Integr Comp Physiol. 2012;302:R233–R241. (Epub 11/11/2011).CrossRefPubMedGoogle Scholar
  16. 16.
    Stengel A, Goebel-Stengel M, Wang L, Kato I, Mori M, Tache Y. Nesfatin-1(30–59) but not the N- and C-terminal fragments, nesfatin-1(1–29) and nesfatin-1(60–82) injected intracerebroventricularly decreases dark phase food intake by increasing inter-meal intervals in mice. Peptides. 2012;35:143–148. (Epub 06/12/2012).CrossRefPubMedCentralPubMedGoogle Scholar
  17. 17.
    Merali Z, Cayer C, Kent P, Anisman H. Nesfatin-1 increases anxiety- and fear-related behaviors in the rat. Psychopharmacology. 2008;201:115–123. (Epub 08/02/2008).CrossRefPubMedGoogle Scholar
  18. 18.
    Stengel A, Goebel M, Tache Y. Nesfatin-1: a novel inhibitory regulator of food intake and body weight. Obes Rev Off J Int Assoc Study Obes. 2011;12:261–271. (Epub 06/16/2010).CrossRefGoogle Scholar
  19. 19.
    Stengel A, Tache Y. Nesfatin-1—role as possible new potent regulator of food intake. Regul Pept. 2010;163:18–23. (Epub 06/29/2010).CrossRefPubMedCentralPubMedGoogle Scholar
  20. 20.
    Xia ZF, Fritze DM, Li JY, et al. Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats. Am J Physiol Gastrointest Liver Physiol. 2012;303:G570–G577. (Epub 06/23/2012).CrossRefPubMedCentralPubMedGoogle Scholar
  21. 21.
    Itoh Z, Takeuchi S, Aizawa I, et al. Changes in plasma motilin concentration and gastrointestinal contractile activity in conscious dogs. Am J Dig Dis. 1978;23:929–935. (Epub 10/01/1978).CrossRefPubMedGoogle Scholar
  22. 22.
    Bormans V, Peeters TL, Janssens J, Pearce D, Vandeweerd M, Vantrappen G. In man, only activity fronts that originate in the stomach correlate with motilin peaks. Scand J Gastroenterol. 1987;22:781–784. (Epub 09/01/1987).CrossRefPubMedGoogle Scholar
  23. 23.
    Kerbel B, Unniappan S. Nesfatin-1 suppresses energy intake, co-localises ghrelin in the brain and gut, and alters ghrelin, cholecystokinin and orexin mRNA expression in goldfish. J Neuroendocrinol. 2012;24:366–377. (Epub 10/26/2011).CrossRefPubMedGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2015

Authors and Affiliations

  • Akira Watanabe
    • 1
    • 3
    Email author
  • Erito Mochiki
    • 2
  • Akiharu Kimura
    • 1
  • Norimichi Kogure
    • 1
  • Mitsuhiro Yanai
    • 1
  • Atsushi Ogawa
    • 1
  • Yoshitaka Toyomasu
    • 1
  • Kyoichi Ogata
    • 1
  • Tetsuro Ohno
    • 1
  • Hideki Suzuki
    • 1
  • Hiroyuki Kuwano
    • 1
  1. 1.Department of General Surgical ScienceGunma University Graduate School of MedicineMaebashiJapan
  2. 2.Department of Digestive Tract and General Surgery, Saitama Medical CenterSaitama Medical UniversityKawagoeJapan
  3. 3.Department of General Surgical Science (Surgery I)Gunma University Graduate School of MedicineMaebashiJapan

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