Nesfatin-1 Suppresses Energy Intake, Co-localises Ghrelin in the Brain and Gut, and Alters Ghrelin, Cholecystokinin and Orexin mRNA Expression in Goldfish


Dr S. Unniappan, Department of Biology, 221 Lumbers Building, 4700 Keele Street, York University, Toronto, Ontario M3J1P3, Canada (e-mail:


Nesfatin-1 is a novel anorectic peptide encoded in the precursor protein nucleobindin-2 (NUCB2). We recently reported the presence and appetite suppressing effects of nesfatin-1 in goldfish. Nesfatin-1 has been co-localised with ghrelin in the stomach of rats. Whether nesfatin-1 influences other appetite regulatory peptides in goldfish remains unclear. The main objectives of the present study were to investigate whether nesfatin-1 co-localises ghrelin in goldfish, and to test whether exogenous nesfatin-1 influences endogenous ghrelin, cholecystokinin (CCK) and orexin A (OXA). We found co-localisation of nesfatin-1-like and ghrelin-like immunoreactivity in the enteroendocrine cells of the goldfish anterior intestine (J-loop). Furthermore, co-localisation of ghrelin and nesfatin-1 was also observed in the posterior nucleus lateralis tuberis of the goldfish hypothalamus, a brain region implicated in the regulation of food intake. These findings suggest a functional relationship between ghrelin and nesfatin-1 in goldfish. In support of this, i.c.v. administration of goldfish (gf) nesfatin-1 [25 ng/g body weight (BW)], suppressed food intake and the expression of mRNAs encoding preproghrelin, ghrelin receptor (GHS-R 1a-1), CCK and NUCB2 in the forebrain of fed fish, as well as ghrelin and NUCB2 mRNA in the hypothalamus of unfed fish, both at 1 h post-injection. Nesfatin-1 stimulated hypothalamic CCK mRNA expression at 30 min post-injection in fed fish, and inhibited OXA mRNA in the unfed fish hypothalamus 1 h post-injection. Similarly, i.c.v. injections of gfghrelin (1 ng/g BW), although stimulating food intake, suppressed NUCB2 and preproghrelin mRNAs, but not ghrelin receptor mRNA expression in the forebrain. It is also evident that exogenous ghrelin and nesfatin-1 mRNAs encoding these peptides. Our novel results indicate interactions between nesfatin-1 and ghrelin, CCK and orexin, and show that nesfatin-1 acts on other appetite regulatory peptides in a time- and feeding status-dependent, as well as tissue-specific, manner in goldfish.