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Simple Summary: Enhanced feeding can be associated with aggressive behaviour since food resources are the main reason for agonistic behaviour (any social behaviour related to fighting). The overexpression of the gene agouti-signalling protein (Asip1) in transgenic zebrafish (asip1-Tg) results in enhanced food intake and linear growth. Our next question was if asip1-Tg animals exhibit a dominant phenotype associated with the feeding-enhanced levels when compared to wild-type (WT) fish. To address this question, we quantified the aggressive behaviour by conducting dyadic fights with real opponents as well as by exposing the animals to their specular image using mirrors. The results indicate that asip1-Tg are less aggressive than WT zebrafish in both dyadic fights and mirror-stimulus tests. These findings provide direct evidence of the role of the melanocortin system in the regulation of fish behaviour. The subordinate personality observed in asip1-Tg suggests that this transgene would be non-threatening to native populations in the event of an escape from aquaculture facilities. These results provide a genetic modification strategy to enhance growth in fish through high feeding motivation without promoting aggressiveness. This suggests that inhibiting the melanocortin system could be a viable target for genetically engineered fish. It is worth noting that the regulatory approval for such genetically engineered fish would be subject to the guidelines and regulations of the U.S. Food and Drug Association. Feeding motivation plays a crucial role in food intake and growth. It closely depends on hunger and satiation, which are controlled by the melanocortin system. Overexpression of the inverse agonist agouti-signalling protein (ASIP) and agouti-related protein (AGRP) leads to enhanced food intake, linear growth, and weight. In zebrafish, overexpression of Agrp leads to the development of obesity, in contrast to the phenotype observed in transgenic zebrafish that overexpress asip1 under the control of a constitutive promoter (asip1-Tg). Previous studies have demonstrated that asip1-Tg zebrafish exhibit larger sizes but do not become obese. These fish display increased feeding motivation, resulting in a higher feeding rate, yet a higher food ration is not essential in order to grow larger than wild-type (WT) fish. This is most likely attributed to their improved intestinal permeability to amino acids and enhanced locomotor activity. A relationship between high feeding motivation and aggression has been previously reported in some other transgenic species showing enhanced growth. This study aims to elucidate whether the hunger observed in asip1-Tg is linked to aggressive behaviour. Dominance and aggressiveness were quantified using dyadic fights and mirror-stimulus tests, in addition to the analysis of basal cortisol levels. The results indicate that asip1-Tg are less aggressive than WT zebrafish in both dyadic fights and mirror-stimulus tests. [ABSTRACT FROM AUTHOR]

Evidence indicates that central regulation of food intake is well conserved along the vertebrate lineage, at least between teleost fish and mammals. However, several differences arise in the comparison between both groups. In this review, we describe similarities and differences between teleost fish and mammals on an evolutionary perspective. We focussed on the existing knowledge of specific fish features conditioning food intake, anatomical homologies and analogies between both groups as well as the main signalling pathways of neuroendocrine and metabolic nature involved in the homeostatic and hedonic central regulation of food intake. [ABSTRACT FROM AUTHOR]

There is no information available on fish as far as the possible effects of ghrelin on hypothalamic fatty acid metabolism and the response of fatty acid-sensing systems, which are involved in the control of food intake. Therefore, we assessed in rainbow trout the response of food intake, hypothalamic fatty acid-sensing mechanisms and expression of neuropeptides involved in the control of food intake to the central treatment of ghrelin in the presence or absence of a long-chain fatty acid such as oleate. We observed that the orexigenic actions of ghrelin in rainbow trout are associated with changes in fatty acid metabolism in the hypothalamus and an inhibition of fatty acid-sensing mechanisms, which ultimately lead to changes in the expression of anorexigenic and orexigenic peptides resulting in increased orexigenic potential and food intake. Moreover, the response to increased levels of oleate of hypothalamic fatty acid-sensing systems (activation), expression of neuropeptides (enhanced anorexigenic potential) and food intake (decrease) were counteracted by the simultaneous treatment with ghrelin. These changes provide evidence for the first time in fish of a possible modulatory role of ghrelin on the metabolic regulation by fatty acid of food intake occurring in the hypothalamus. [ABSTRACT FROM AUTHOR]

Summary: This study is the third part of a comprehensive series of publications on the cytoarchitectonic organization of the brain of the European sea bass, Dicentrarchus labrax. This study provides an atlas of the brain stem based on Nissl-stained transverse sections as well as a description of cell masses and a discussion on comparative aspects of brain stem nuclei, including methodological studies in other species. By external examination, the sea bass exhibits a prominent Optic tectum and Corpus cerebelli as expected in a predator species with a highly developed visual system. However, no hypertrophy of the facial and vagal lobes was observed as reported in other non-perciform teleosts. The general organization pattern of the mesencephalon and rhombencephalon of the sea bass brain resembles that reported for other perciform teleosts. However, the Valvula cerebelli has been subdivided into anterior, central and posterior parts. In addition, the ventricular surface of the granular layer of the Valvula cerebelli appears to be in contact with those of the Torus longitudinalis. This cell apposition could be interpreted as a direct connection, but more studies demonstrating the absence of ependyma between both structures are needed. Furthermore, we have tentatively described the electro/mechano receptive pre-eminential nucleus in the rhombencephalon of the sea bass. This study completes one of the few descriptions, as well as the most complete and detailed available, of the brain of any marine perciform species. [Copyright &y& Elsevier]

Abstract: Three different estrogen receptors (ERs) have been cloned and characterized in teleosts fish, i.e. ERα, ERβ or ERβ1 and ERγ or ERβ2. In order to study the sea bass ER subtype involved in the regulation of gonadotropin production, as well as to elucidate the possible involved neuronal pathways, we characterized the transactivation properties of the cloned sea bass ERα (sbERα) and studied its distribution in the brain and gonadotropic cells of the sea bass by in situ hybridization. The results revealed that sbERα transactivates promoters containing estradiol responsive elements (ERE) in a dose–response manner. The sbERα showed the highest affinity for 17-β-estradiol. In situ hybridization studies demonstrated that ERα mRNA positive neurons are widely distributed within the sea bass brain, including the telencephalon, preoptic area, thalamus, hypothalamus, mesencephalic tectum and tegmentum and rhombencephalon. New estrogen dependent nuclei were described in all above areas. The sbERα was profusely expressed in the main neuroendocrine areas such as the preoptic area and hypothalamus, thus suggesting the steroidal modulation of the hypophysiotropic neurons. The presence of sbERα expression in the FSHβ and LHβ cells suggests a direct effect of estrogens in the control of gonadotropin hormone synthesis. [Copyright &y& Elsevier]

In this paper, we report (i) the in situ localization, and (ii) meal time related and starvation induced changes in preprogalanin mRNA expression in the goldfish brain. The specific brain nuclei that express galanin mRNA are the area ventralis telencephali pars ventralis, nucleus preopticus periventricularis, nucleus lateralis tuberis, and the nucleus recessus lateralis. No changes in preprandial preprogalanin mRNA expression were found in the brain regions studied. No changes in postprandial preprogalanin mRNA expression were found compared to the preprandial levels. However, in unfed fish, a significant increase in preprogalanin mRNA expression was found in the telencephalon (1 and 3 h) and hypothalamus (3 h) after the scheduled feeding time. The postprandial preprogalanin mRNA expression in the telencephalon and hypothalamus of fed fish at 1 and 3 h were significantly lower than the mRNA expression levels in the unfed fish at the same time. Preprogalanin mRNA expression levels remain unaltered during 7 days of starvation. The presence of preprogalanin mRNA in brain nuclei involved in the regulation of food intake and pituitary hormone secretion suggests important physiological roles for galanin in goldfish. [Copyright &y& Elsevier]

The melanocortin system is a complex neuroendocrine signaling mechanism involved in numerous physiological processes in vertebrates, including pigmentation, steroidogenesis and metabolic control. This review focuses at one of its most fascinating function in fish, its regulatory role in the control of pigmentation, in which the melanocortin 1 receptor (Mc1r), its agonist α-melanocyte stimulating hormone (α-Msh), and the endogenous antagonist agouti signaling protein (Asip1) are the main players. Functional control of Mc1r, which is highly expressed in fish skin and whose activation stimulates melanin production and melanosome dispersion in fish melanophores, is considered a key mechanism for vertebrate pigment phenotypes. The α-Msh peptide, the most documented Mc1r agonist involved in pigmentation, is produced in the pituitary gland, activating melanin synthesis by binding to Mc1r in fish melanophores. Finally, Asip1 is the putative factor for establishing the evolutionarily conserved dorso-ventral pigment pattern found across vertebrates. However, we are just starting to understand how other melanocortin system components are acting in this complex regulatory network. [ABSTRACT FROM AUTHOR]

The melanocortin system is one of the most complex hormonal systems in vertebrates. Atypically, the signaling of melanocortin receptors is regulated by the binding of endogenous antagonists, named agouti-signaling protein (ASIP) and agouti-related protein (AGRP). Teleost specific genome duplication (TSGD) rendered new gene copies in teleost fish and up to four different genes of the agouti family of peptides have been characterized. In this paper, molecular cloning was used to characterize mRNA of the agouti family of peptides in sea bass. Four different genes were identified: AGRP1, ASIP1, AGRP2 and ASIP2. The AGRP1 gene is mainly expressed in the brain whereas ASIP1 is mainly expressed in the ventral skin. Both ASIP2 and AGRP2 are expressed in the brain and the pineal gland but also in some peripheral tissues. Immunocytochemical studies demonstrated that AGRP1 is exclusively expressed within the lateral tuberal nucleus, the homologue of the mammalian arcuate nucleus in fish. Long-term fasting (8–29 days) increased the hypothalamic expression of AGRP1 but depressed AGRP2 expression (15–29 days). In contrast, the hypothalamic expression of ASIP2 was upregulated during short-term fasting suggesting that this peptide could be involved in the short term regulation of food intake in the sea bass. [ABSTRACT FROM AUTHOR]

Abstract: Dopamine is synthesized from l-dopa and subsequently processed into norepinephrine and epinephrine. Any excess neurotransmitter can be taken up again by the neurons to be broken down enzymatically into DOPAC. The effect of dopamine on mammalian food intake is controversial. Mice unable to synthesize central dopamine die of starvation. However, studies have also shown that central injection of dopamine inhibits food intake. The effect of dopaminergic system in the fish feeding behavior has been scarcely explored. We report that the inclusion of l-dopa in the diets results in the activation of sea bass central dopaminergic system but also in the significant increase of the hypothalamic serotonin levels. Dietary l-dopa induces a decrease of food intake and feed conversion efficiency that drives a decline of all growth parameters tested. No behavioral effects were observed after l-dopa treatment. l-dopa treatment stimulated central expression of NPY and CRF. It suggests that CRF might mediate l-dopa effects on food intake but also that CRF neurons lie downstream of NPY neurons in the hierarchical forebrain system, thus controlling energy balance. Unexpectedly, dietary administration of haloperidol, a D2-receptor antagonist, cannot block dopamine effects but also induces a decline of the food intake. This decrease seems to be a side effect of haloperidol treatment since fish exhibited a decreased locomotor activity. We conclude that oral l-dopa inhibits sea bass food intake and growth. Mechanism could also involve an increase of hypothalamic serotoninergic tone. [Copyright &y& Elsevier]

Abstract: In this paper, we identify three different MRAPs in zebrafish, zfMRAP1, zfMRAP2a and zfMRAP2b, and demonstrate that zfMC2R is not functional in the absence of MRAP expression. ZfMRAP1 expression was restricted to adipose tissue and the anterior kidney whereas MRAP2a and MRAP2b were expressed in all the tissues tested. Quantification of surface receptor and immunofluorescence studies indicated that the receptor is unable to translocate to membrane in the absence of MRAP isoforms. MRAP1 and MRAP2b are localized in the plasma membrane in the absence of zfMC2R expression but MRAP2b is retained in perinuclear position. MRAP1 and MRAP2a displayed an equivalent translocation capacity to the membrane of zfMC2R but only zfMRAP1 expression led to intracellular cAMP increases after ACTH stimulation. ZfMRAP2b had no effect on zfMC2R activity but both zfMRAP2 isoforms enhanced the zfMRAP1-assisted cAMP intracellular increase, suggesting an interaction between zfMRAP1 and zfMRAP2s when regulating zfMC2R activity. [Copyright &y& Elsevier]

Abstract: Three different estrogen receptors (ERs) have been characterized in teleost fish, i.e. Esr1, Esr2a and Esr2b. In this study we carried out in situ hybridizations in the brain and pituitary of the sea bass (Dicentrarchus labrax) to study the putative involvement of Esr2 subtypes in the control of gonadotropin secretion in fish. Our studies demonstrated that both receptors are expressed within the main hypophysiotrophic areas of the sea bass brain thus providing neuroanatomical basis for the involvement of Esr2 subtypes in the long (or indirect) regulatory feedbacks on pituitary function in the sea bass. The results revealed that Esr2b-mRNA distribution was restricted to the preoptic area and tuberal hypothalamus. On the contrary, Esr2a presented a widespread distribution and transcripts were detected within the ventral telencephalon, preoptic area, hypothalamus, thalamus, posterior tubercle, mesencephalon and rhombencephalon. New Esr2-expressing areas were described in all of the above areas. This paper is the first demonstration of Esr2a and Esr2b expression in the follicle-stimulating hormone β-subunit (βFSH)- and luteinizing hormone β-subunit (βLH)-expressing cells in the fish pituitary, thus suggesting the participation of both receptors in the direct effect of estrogen on the control of gonadotropin hormone synthesis. [Copyright &y& Elsevier]