title: Nesfatin-1 induces Fos expression and elicits dipsogenic responses in subfornical organ.
abstract: Nesfatin-1 (Nes-1), an 82-amino acid protein cleaved from nucleobindin-2, has been suggested to play a role in ingestive behaviors. Intracerebroventricular (icv) injections of Nes-1 reduce water intake, although the sites of action for this effect are not known. Two series of experiments were done to identify potential sites of action of Nes-1 in drinking behavior. In the first series, icv injections of Nes-1 were made in urethane-anesthetized rats to investigate the distribution of neurons containing Fos-like immunoreactivity (Fos-ir) within the forebrain. Circumventricular organs, including subfornical organ (SFO), were found to contain neurons expressing Fos-ir. Additionally, several hypothalamic, thalamic and limbic nuclei also contained Fos-labeled neurons. As SFO is a pivotal central site in the regulation of water intake, a second series of experiments was done to investigate the role of direct injections of Nes-1 into SFO on water intake in conscious, freely moving rats. Nes-1 (2pmol) injections into SFO induced an increase in water intake compared to vehicle injections. However, when food was made available for ingestion after the Nes-1 injection, the dipsogenic effects of Nes-1 were attenuated. Additionally, the drinking response to Nes-1 was found to be more potent than that observed after injections of ANG II into SFO. Neither simultaneous injections ANG II nor the ANG II type-1 receptor blocker losartan affected the Nes-1 dipsogenic response. Taken together, these results suggest that Nes-1 is a potent dipsogenic agent in SFO, and that Nes-1 may act independently of the SFO angiotensinergic system to elicit the dipsogenic effect.
authors.affiliation: Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada N6A 5C1.
authors.forename: Jason M
authors.initials: JM
authors.lastname: Moreau
authors.forename: John
authors.initials: J
authors.lastname: Ciriello
mesh_terms: D000704:Analysis of Variance; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002135:Calcium-Binding Proteins / Q000494:pharmacology*; D004268:DNA-Binding Proteins / Q000494:pharmacology*; D004435:Eating / Q000187:drug effects*; D007276:Injections, Intraventricular / Q000379:methods; D008297:Male; D009419:Nerve Tissue Proteins / Q000494:pharmacology*; D009434:Neural Pathways / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000378:metabolism; D000080866:Nucleobindins; D016548:Prosencephalon / Q000166:cytology / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013356:Subfornical Organ / Q000166:cytology / Q000187:drug effects*; D013997:Time Factors; D014851:Wakefulness
chemical_list: D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D009419:Nerve Tissue Proteins; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D016760:Proto-Oncogene Proteins c-fos; D000804:Angiotensin II