title: Behind melanocortin antagonist overexpression in the zebrafish brain: A behavioral and transcriptomic approach.
abstract: Melanocortin signaling is regulated by the binding of naturally occurring antagonists, agouti-signaling protein (ASIP) and agouti-related protein (AGRP) that compete with melanocortin peptides by binding to melanocortin receptors to regulate energy balance and growth. Using a transgenic model overexpressing ASIP, we studied the involvement of melanocortin system in the feeding behaviour, growth and stress response of zebrafish. Our data demonstrate that ASIP overexpression results in enhanced growth but not obesity. The differential growth is explained by increased food intake and feeding efficiency mediated by a differential sensitivity of the satiety system that seems to involve the cocaine- and amphetamine- related transcript (CART). Stress response was similar in both genotypes. Brain transcriptome of transgenic (ASIP) vs wild type (WT) fish was compared using microarrays. WT females and males exhibited 255 genes differentially expressed (DEG) but this difference was reduced to 31 after ASIP overexpression. Statistical analysis revealed 1122 DEG when considering only fish genotype but 1066 and 981 DEG when comparing ASIP males or females with their WT counterparts, respectively. Interaction between genotype and sex significantly affected the expression of 97 genes. Several neuronal systems involved in the control of food intake were identified which displayed a differential expression according to the genotype of the fish that unravelling the flow of melanocortinergic information through the central pathways that controls the energy balance. The information provided herein will help to elucidate new central systems involved in control of obesity and should be of invaluable use for sustaining fish production systems.
authors.affiliation: Control of Food Intake Group, Department of Fish Physiolgy and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595.
authors.forename: Raúl
authors.initials: R
authors.lastname: Guillot
authors.affiliation: Control of Food Intake Group, Department of Fish Physiolgy and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595.
authors.forename: Raúl
authors.initials: R
authors.lastname: Cortés
authors.affiliation: Control of Food Intake Group, Department of Fish Physiolgy and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595.
authors.forename: Sandra
authors.initials: S
authors.lastname: Navarro
authors.affiliation: Control of Food Intake Group, Department of Fish Physiolgy and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595.
authors.forename: Morena
authors.initials: M
authors.lastname: Mischitelli
authors.affiliation: Control of Food Intake Group, Department of Fish Physiolgy and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595.
authors.forename: Víctor
authors.initials: V
authors.lastname: García-Herranz
authors.affiliation: Control of Food Intake Group, Department of Fish Physiolgy and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595.
authors.forename: Elisa
authors.initials: E
authors.lastname: Sánchez
authors.affiliation: Aquatic Molecular Pathobiology Group, Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (CSIC), Vigo, Spain.
authors.forename: Laura
authors.initials: L
authors.lastname: Cal
authors.affiliation: Lipid Group, Department of Biology, Culture and Pathology of Marine Species, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595.
authors.forename: Juan Carlos
authors.initials: JC
authors.lastname: Navarro
authors.affiliation: Laboratorio de Fisioloxía Animal, Departamento de Bioloxía Funcional e Ciencias da Saúde, Facultade de Bioloxía, Universidade de Vigo, Vigo, Spain, 36310.
authors.forename: Jesús M
authors.initials: JM
authors.lastname: Míguez
authors.affiliation: Sechenov Institute of Evolutionary Physiology and Biochemistry, M. Toreza Av. 44, Saint Petersburg 194223, Russia.
authors.forename: Sergey
authors.initials: S
authors.lastname: Afanasyev
authors.affiliation: Nofima Marine, Norwegian Institutes of Food, Fisheries & Aquaculture Research, 5010 1432 Ås, Norway.
authors.forename: Aleksei
authors.initials: A
authors.lastname: Krasnov
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 702 Light Hall (0165),, Nashville, TN 37232-0165, United States.
authors.forename: Roger D
authors.initials: RD
authors.lastname: Cone
authors.affiliation: Aquatic Molecular Pathobiology Group, Instituto de Investigaciones Marinas, Consejo Superior de Investigaciones Científicas (CSIC), Vigo, Spain. Electronic address: rotllant@iim.csic.es.
authors.forename: Josep
authors.initials: J
authors.lastname: Rotllant
authors.affiliation: Control of Food Intake Group, Department of Fish Physiolgy and Biotechnology, Instituto de Acuicultura de Torre de la Sal (IATS-CSIC), Castellón, Spain, 12595. Electronic address: jm.cerda.reverter@csic.es.
authors.forename: Jose Miguel
authors.initials: JM
authors.lastname: Cerdá-Reverter
mesh_terms: D054366:Agouti Signaling Protein / Q000235:genetics* / Q000378:metabolism; D054369:Agouti-Related Protein / Q000235:genetics / Q000378:metabolism; D000818:Animals; D030801:Animals, Genetically Modified; D001921:Brain / Q000378:metabolism*; D004435:Eating / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics; D005247:Feeding Behavior / Q000502:physiology; D005260:Female; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D008297:Male; D053486:Melanocortins / Q000037:antagonists & inhibitors; D009434:Neural Pathways / Q000378:metabolism; D015027:Zebrafish / Q000235:genetics* / Q000378:metabolism
chemical_list: D054366:Agouti Signaling Protein; D054369:Agouti-Related Protein; D053486:Melanocortins
keywords: Agouti-related protein (AGRP); Agouti-signaling protein (ASIP); Brain; Food intake; Growth; Melanocortin receptor; Sex-dimorphism; Stress; Transcriptome