Nesfatin-1 suppresses energy intake, co-localises ghrelin in the brain and gut, and alters ghrelin, cholecystokinin and orexin mRNA expression in goldfish.
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.
Laboratory of Integrative Neuroendocrinology, Department of Biology, York University, Toronto, Ontario, Canada.
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Kerbel
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Unniappan
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000378:metabolism*; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002766:Cholecystokinin / Q000235:genetics* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002149:Energy Intake / Q000187:drug effects* / Q000235:genetics; D015870:Gene Expression / Q000187:drug effects; D054439:Ghrelin / Q000378:metabolism*; D006054:Goldfish / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D007413:Intestinal Mucosa / Q000378:metabolism*; D007422:Intestines / Q000187:drug effects; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics* / Q000378:metabolism; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D009479:Neuropeptides / Q000235:genetics* / Q000378:metabolism; D000080866:Nucleobindins; D000068797:Orexins; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D014018:Tissue Distribution
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D054439:Ghrelin; D047908:Intracellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D009479:Neuropeptides; C000630652:Nucb1 protein, rat; D000080866:Nucleobindins; D000068797:Orexins; D012333:RNA, Messenger; D002766:Cholecystokinin