Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats

Ze Feng Xia, Danielle M. Fritze, Ji Yao Li, Biaoxin Chai, Chao Zhang, Weizhen Zhang, Michael W. Mulholland

Research output: Contribution to journalArticlepeer-review

39 Scopus citations

Abstract

Nesfatin-1, a novel hypothalamic peptide, inhibits nocturnal feeding behavior and gastrointestinal motility in rodents. The effects of nesfatin-1 on gastrointestinal secretory function, including gastric acid production, have not been evaluated. Nesfatin-1 was injected into the fourth intracerebral ventricle (4V) of chronically cannulated rats to identify a nesfatin dose sufficient to inhibit food intake. Nesfatin-1 (2 μg) inhibited dark-phase food intake, in a dose-dependent fashion, for >3 h. Gastric acid production was evaluated in urethane-anesthetized rats. Nesfatin-1 (2 μg) was introduced via the 4V following endocrine stimulation of gastric acid secretion by pentagastrin (2 μg·kg-1·h-1 iv), vagal stimulation with 2-deoxy-D-glucose (200 mg/kg sc), or no stimulus. Gastric secretions were collected via gastric cannula and neutralized by titration to determine acid content. Nesfatin-1 did not affect basal and pentagastrin- stimulated gastric acid secretion, whereas 2-deoxy-D-glucosestimulated gastric acid production was inhibited by nesfatin-1 in a dose-dependent manner. c-Fos immunofluorescence in brain sections was used to evaluate in vivo neuronal activation by nesfatin-1 administered via the 4V. Nesfatin-1 caused activation of efferent vagal neurons, as evidenced by a 16-fold increase in the mean number of c-Fos-positive neurons in the dorsal motor nucleus of the vagus (DMNV) in nesfatin-1-treated animals vs. controls (P < 0.01). Finally, nesfatin-induced Ca2+ signaling was evaluated in primary cultured DMNV neurons from neonatal rats. Nesfatin-1 caused dosedependent Ca2+ increments in 95% of cultured DMNV neurons. These studies demonstrate that central administration of nesfatin-1, at doses sufficient to inhibit food intake, results in inhibition of vagally stimulated secretion of gastric acid. Nesfatin-1 activates DMNV efferent vagal neurons in vivo and triggers Ca2+ signaling in cultured DMNV neurons.

Original languageEnglish (US)
Pages (from-to)G570-G577
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume303
Issue number5
DOIs
StatePublished - Sep 1 2012
Externally publishedYes

Keywords

  • Dorsal motor nucleus of the vagus
  • Gastric hormones
  • Intracellular calcium

ASJC Scopus subject areas

  • Physiology
  • Hepatology
  • Gastroenterology
  • Physiology (medical)

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