Nesfatin-1 suppresses feeding and induces emesis in Suncus murinus (house musk shrew)

Abstract

Introduction: Nesfatin-1 is an 82-amino acid anorectic peptide derived from nucleobindin2 (NUCB2). NUCB2/nesfatin-1 is expressed in peripheral tissues and also in brain areas involved in the regulation of feeding, emotion and emesis. However, the potential involvement of nesfatin-1 in emesis control is essentially unknown.

Aims: The present studies examine the effect of a central administration of nesfatin-1 on feeding, emesis and locomotor activity in Suncus murinus.

Methods: Animals were anaesthetised with sodium pentobarbitone (40 mg/kg, i.p.) and then stereotaxically implanted with a guide cannula into the lateral ventricle and allowed a 7-days recovery before experimentation. Animals were fasted 12 h prior to administration of drugs. Nesfatin-1 (1-50 pmol, i.c.v.) or saline (5 μl, i.c.v.) was administered to conscious fasted animals. 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.

Results: Compared to saline-treated animals, nesfatin-1 (5 pmol, i.c.v.) suppressed the amount of food eaten at 4-, 5- and 6-h by 30.9%, 32.9%, and 29.4%, respectively (P<0.01; cumulative measurements), but it failed to affect 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); higher doses (5-50 pmol) had no effect. No statistically significant differences in the 24-h cumulative food and water intake between treatment groups were found. Additionally, nesfatin-1 at 5 pmol i.c.v. induced emesis in 5 out of 6 animals with 7.5 ± 4.4 retches + vomits following a median latency of 39.7 min (P<0.05). Nesfatin-1 had no effect on the locomotor activity.

Discussion: To the best of our knowledge, nesfatin-1 is the most potent peptide to induce emesis and inhibit feeding in S. murinus. 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).