The role of nesfatin-1 in the regulation of feeding and emesis in Suncus murinus (house musk shrew)
Author(s)
Lu, Zengbing
Author(s)
Sakata, I.
Sakai, T.
Liu, J. Y.
Lin, G.
Rudd, J. A.
Date Issued
2018
Conference
18th World Congress of Basic and Clinical Pharmacology (WCP2018)
Abstract
Introduction. Nesfatin-1 is a recently discovered 82-amino acid peptide derived from nucleobindin2 (NUCB2). NUCB2/nesfatin-1 is widely distributed in brain areas involved in the regulation of feeding, emotion and emesis.
Aims. In the present studies, we identified the amino acid sequence of nesfatin-1 in Suncus murinus (SM). We investigated the action of nesfatin-1 to affect locomotor activity, feeding and emesis, and gastrointestinal contractility. Methods. The amino acid sequence of SM nesfatin-1 was determined using in silico cloning. In in vivo studies, nesfatin-1 (1-50 pmol, i.c.v.) or saline (5 µl, i.c.v.) was administered to conscious animals after an overnight fast. Emesis and spontaneous behaviour were measured for 6 h, while food and water consumption was measured hourly for 6 h and at 24 h post-administration. The potential action of nesfatin-1 on the ileum was investigated in vitro using an isolated organ bath setup. Results. The amino acid sequence of SM nesfatin-1 showed high homology with humans, rats and mice (86.6% to humans and rats; 85.4% to mice). The administration of nesfatin-1 at 5 pmol, i.c.v., suppressed cumulative food intake at 4 to 6 h (～30% reduction compared to controls; P<0.01; cumulative measurements), without affecting the latency to eat (P>0.05). Nesfatin-1 at 1 pmol, i.c.v. suppressed cumulative water intake assessed at 5 h (P<0.05). Nesfatin-1 at 25 pmol, i.c.v. suppressed cumulative food and water intake at 24 h by 28.3% and 35.4%, respectively (P<0.01). In addition, nesfatin-1 at 5 pmol, i.c.v. induced emesis in 5 out of 6 animals (18.8 ± 8.3 retches and 4.7 ± 2.1 vomits; P<0.05), following a median latency of 40 min (P<0.05). Nesfatin-1 had no effect on locomotor activity and also failed to contract or relax the isolated ileum. Conclusions. Nesfatin-1 is highly conserved in SM, humans, rats and mice. To the best of our knowledge, nesfatin-1 is the most potent peptide to induce emesis and inhibit feeding in SM. The studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/16).
Aims. In the present studies, we identified the amino acid sequence of nesfatin-1 in Suncus murinus (SM). We investigated the action of nesfatin-1 to affect locomotor activity, feeding and emesis, and gastrointestinal contractility. Methods. The amino acid sequence of SM nesfatin-1 was determined using in silico cloning. In in vivo studies, nesfatin-1 (1-50 pmol, i.c.v.) or saline (5 µl, i.c.v.) was administered to conscious animals after an overnight fast. Emesis and spontaneous behaviour were measured for 6 h, while food and water consumption was measured hourly for 6 h and at 24 h post-administration. The potential action of nesfatin-1 on the ileum was investigated in vitro using an isolated organ bath setup. Results. The amino acid sequence of SM nesfatin-1 showed high homology with humans, rats and mice (86.6% to humans and rats; 85.4% to mice). The administration of nesfatin-1 at 5 pmol, i.c.v., suppressed cumulative food intake at 4 to 6 h (～30% reduction compared to controls; P<0.01; cumulative measurements), without affecting the latency to eat (P>0.05). Nesfatin-1 at 1 pmol, i.c.v. suppressed cumulative water intake assessed at 5 h (P<0.05). Nesfatin-1 at 25 pmol, i.c.v. suppressed cumulative food and water intake at 24 h by 28.3% and 35.4%, respectively (P<0.01). In addition, nesfatin-1 at 5 pmol, i.c.v. induced emesis in 5 out of 6 animals (18.8 ± 8.3 retches and 4.7 ± 2.1 vomits; P<0.05), following a median latency of 40 min (P<0.05). Nesfatin-1 had no effect on locomotor activity and also failed to contract or relax the isolated ileum. Conclusions. Nesfatin-1 is highly conserved in SM, humans, rats and mice. To the best of our knowledge, nesfatin-1 is the most potent peptide to induce emesis and inhibit feeding in SM. The studies were fully supported by a grant from the Research Grants Council of the Hong Kong SAR, China (Project no. UGC/FDS11/M02/16).
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Yes
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