Ghrelin suppresses cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) in the intestine, and attenuates the anorectic effects of CCK, PYY and GLP-1 in goldfish (Carassius auratus).
Blanco, A. M., Bertucci, J. I., Valenciano, A. I., Delgado, M. J. and Unniappan, S.
Departamento de Fisiologia (Fisiologia Animal II), Facultad de Biologia, Universidad Complutense de Madrid, Jose Antonio Novais 12, 28040 Madrid, Spain; Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, S7N 5B4 Saskatoon, Saskatchewan, Canada. Electronic address: ayelenmelisablanco@ucm.es.
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, S7N 5B4 Saskatoon, Saskatchewan, Canada; Instituto de Investigaciones Biotecnologicas-Instituto Tecnologico Chascomus, Avenida Intendente Marinos Km. 8,2, 7130 Chascomus, Buenos Aires, Argentina. Electronic address: jbertucci@intech.gov.ar.
Departamento de Fisiologia (Fisiologia Animal II), Facultad de Biologia, Universidad Complutense de Madrid, Jose Antonio Novais 12, 28040 Madrid, Spain. Electronic address: aivalenciano@bio.ucm.es.
Departamento de Fisiologia (Fisiologia Animal II), Facultad de Biologia, Universidad Complutense de Madrid, Jose Antonio Novais 12, 28040 Madrid, Spain. Electronic address: mjdelgad@bio.ucm.es.
Laboratory of Integrative Neuroendocrinology, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, University of Saskatchewan, 52 Campus Drive, S7N 5B4 Saskatoon, Saskatchewan, Canada. Electronic address: suraj.unniappan@usask.ca.
Ghrelin is an important gut-derived hormone with an appetite stimulatory role, while most of the intestinal hormones, including cholecystokinin (CCK), peptide YY (PYY) and glucagon-like peptide-1 (GLP-1), are appetite-inhibitors. Whether these important peptides with opposing roles on food intake interact to regulate energy balance in fish is currently unknown. The aim of this study was to characterize the putative crosstalk between ghrelin and CCK, PYY and GLP-1 in goldfish (Carassius auratus). We first determined the localization of CCK, PYY and GLP-1 in relation to ghrelin and its main receptor GHS-R1a (growth hormone secretagogue 1a) in the goldfish intestine by immunohistochemistry. Colocalization of ghrelin/GHS-R1a and CCK/PYY/GLP-1 was found primarily in the luminal border of the intestinal mucosa. In an intestinal explant culture, a significant decrease in prepro-cck, prepro-pyy and proglucagon transcript levels was observed after 60min of incubation with ghrelin, which was abolished by preincubation with the GHS-R1a ghrelin receptor antagonist [D-Lys3]-GHRP-6 (except for proglucagon). The protein expression of PYY and GLP-1 was also downregulated by ghrelin. Finally, intraperitoneal co-administration of CCK, PYY or GLP-1 with ghrelin results in no modification of food intake in goldfish. Overall, results of the present study show for the first time in fish that ghrelin exerts repressive effects on enteric anorexigens. It is likely that these interactions mediate the stimulatory effects of ghrelin on feeding and metabolism in fish.
Hormones and Behavior 93: 62-71 (2017)