Behind melanocortin antagonist overexpression in the zebrafish brain: A behavioral and transcriptomic approach
Autor: | Roger D. Cone, Jesús M. Míguez, Aleksei Krasnov, Juan Carlos Navarro, Morena Mischitelli, S. Navarro, José Miguel Cerdá-Reverter, Víctor García-Herranz, Raúl Cortés, Raúl Guillot, Sergey Afanasyev, Josep Rotllant, Elisa Sánchez, Laura Cal |
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Přispěvatelé: | Ministerio de Economía y Competitividad (España) |
Rok vydání: | 2016 |
Předmět: |
Male
0301 basic medicine medicine.medical_specialty Transgene Growth Stress Sex-dimorphism Transcriptomes Animals Genetically Modified Transcriptome Eating 03 medical and health sciences Behavioral Neuroscience Endocrinology Melanocortin receptor Food intake Internal medicine Neural Pathways medicine Animals Agouti-Related Protein Zebrafish Melanocortins Regulation of gene expression biology Endocrine and Autonomic Systems Gene Expression Profiling digestive oral and skin physiology Agouti-related protein (AGRP) Wild type Brain Feeding Behavior biology.organism_classification Agouti-signaling protein (ASIP) 030104 developmental biology Gene Expression Regulation Agouti Signaling Protein Female Melanocortin Energy Metabolism |
Zdroj: | Digital.CSIC. Repositorio Institucional del CSIC instname |
ISSN: | 0018-506X |
Popis: | 14 páginas, 11 figuras.-- Raúl Guillot ... et al. 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 This work was supported by Grants AGL2013-46448-C3-3-R, AGL2013-46448-C3-1-R and AGL2014-52473R from the Spanish Science and Education Ministry (MEC) to J.M.C.-R J.M.M. and J.R. Additional funding was obtained from the Generalitat Valenciana (PROMETEO 2010/006). S.N. and R.C. are recipients a FPI-Chile and FPI fellowships, respectively, from the Spanish Science and Innovation Ministry |
Databáze: | OpenAIRE |
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