M.J. Delgado

Neuropeptide Y has a stimulatory action on feeding behavior in goldfish (Carassius auratus).

The purpose of the present study was to elucidate the possible role of neuropeptide Y (NPY) in the feeding regulation in fish. We examined the effects of intracerebroventricular (i.c.v.) or intraperitoneal (i.p.) neuropeptide Y administration on food intake in satiated goldfish, at different time intervals postinjection (0-2, 2-8 and 0-8 h). Food intake was significantly increased by i.c.v. administered neuropeptide Y (1 microg) at 2 h postinjection, while no significant differences in food intake were observed after i.p. treatment. The neuropeptide Y receptor antagonist, neuropeptide Y-(27-36), totally counteracted the stimulatory action of neuropeptide Y on feeding. The possible involvement of neuropeptide Y in the eating behavior evoked by food deprivation has been investigated. Food deprivation by either 24 or 72 h significantly increased feeding, and the neuropeptide Y receptor antagonist attenuated such feeding stimulation. From our findings, we suggest, first, that neuropeptide Y is involved in feeding central regulation in goldfish, acting via specific neuropeptide Y receptors, and second, that hypothalamic neuropeptide Y would be released in response to food deprivation, contributing to generate the consequent eating behavior stimulation in Carassius auratus.

Vasoactive intestinal peptide in the immune system: potential therapeutic role in inflammatory and autoimmune diseases

Abstract. Vasoactive intestinal peptide (VIP), a neuropeptide that is produced by lymphoid as well as neural cells, exerts a wide spectrum of immunological functions, controlling the homeostasis of the immune system through different receptors expressed in various immunocompetent cells. In the last decade, VIP has been clearly identified as a potent anti-inflammatory factor, which acts by regulating the production of both anti- and pro-inflammatory mediators. In this sense, VIP has been described to prevent death by septic shock, an acute inflammatory disease with a high mortality. In addition, VIP regulates the expression of co-stimulatory molecules, this being an action that may be related to modulating the shift toward Th1 and Th2 differentiation. We have recently reported that VIP prevents the deleterious effects of an experimental model of rheumatoid arthritis, by downregulating both inflammatory and autoimmune components of the disease. Therefore, VIP has been proposed as a promising candidate alternative treatment for acute and chronic inflammatory and autoimmune diseases such as septic shock, arthritis, multiple sclerosis, Crohn disease, or autoimmune diabetes.

Feeding entrainment of locomotor activity rhythms, digestive enzymes and neuroendocrine factors in goldfish.

The existence of food anticipatory activity (FAA) in animals subjected to daily feeding schedules seems to be mediated by a feeding-entrainable oscillator (FEO). Such an FEO may help in anticipating meal time and so optimizing food acquisition and nutrient utilization. In this study we investigated the existence of FAA and whether digestive enzymes, plasma cortisol, hypothalamic NPY and gastrointestinal tract (GIT) and plasma melatonin were entrained by periodic feeding in goldfish. We observed that periodically fed goldfish showed FAA in locomotor activity as well as in amylase and NPY. Alkaline protease and GIT melatonin were higher after feeding, whereas plasma cortisol levels were reduced. Plasma melatonin remained unmodified before and after meal time. These results suggested that scheduled feeding entrained both behavioral and certain physiological patterns in goldfish, FAA being of adaptive value to anticipate a meal and prepare the digestive physiology of fish.

The endocannabinoid system in the brain of Carassius auratus and its possible role in the control of food intake

Cannabinoid receptors and the endocannabinoids anandamide and 2‐arachidonoylglycerol have been suggested to regulate food intake in several animal phyla. Orthologs of the mammalian cannabinoid CB1 and CB2 receptors have been identified in fish. We investigated the presence of this endocannabinoid system in the brain of the goldfish Carassius auratus and its role in food consumption. CB1‐like immunoreactivity was distributed throughout the goldfish brain. The prosencephalon showed strong CB1‐like immunoreactivity in the telencephalon and the inferior lobes of the posterior hypothalamus. Endocannabinoids were detected in all brain regions of C. auratus and an anandamide‐hydrolysing enzymatic activity with features similar to those of mammalian fatty acid amide hydrolase was found. Food deprivation for 24 h was accompanied by a significant increase of anandamide, but not 2‐arachidonoylglycerol, levels only in the telencephalon. Anandamide caused a dose‐dependent effect on food intake within 2 h of intraperitoneal administration to satiated fish and significantly enhanced or reduced food intake at low (1 pg/g body weight) or intermediate (10 pg/g) doses, respectively, the highest dose tested (100 pg/g) being inactive. We suggest that endocannabinoids might variously contribute to adaptive responses to food shortage in fish.

NPY receptors and opioidergic system are involved in NPY-induced feeding in goldfish

The present study evaluated the effects of both intraperitoneal (i.p. ) and intracerebroventricular administration of selective Y(1) [(Leu(31), Pro(34))-NPY] and Y(2) [(Pro(13), Tyr(36))-NPY (13-36)] receptor agonists on food intake in satiated goldfish. Food intake (FI) was significantly increased by central administration of the Y(1) agonist (1 microg), but not by the Y(2) agonist, at 2 h postinjection. The feeding increase induced by (Leu(31), Pro(34))-NPY was in a similar magnitude to that obtained after ICV injection of the neuropeptide Y, and both feeding stimulations were reversed by the NPY (27-36), a general NPY antagonist. The i.p. administration of the agonists either did not significantly modify (Y(2) agonist) or decreased (Y(1) agonist) food intake in goldfish. These data indicate that it is the Y(1)-like (similar to Y(1) and/or Y(5)) receptor, and not Y(2), that is involved in the central modulation of the feeding behavior in goldfish. We also investigated the possible involvement of opioid peptides as mediators of the NPY stimulatory action on food intake in goldfish. The ICV administration of naloxone (10 microg), a general opioid antagonist, blocked the NPY-induced feeding in goldfish, suggesting that the opioidergic system is involved in feeding regulation by NPY.

Effect of α-Helical-CRF[9-41] on feeding in goldfish : Involvement of cortisol and catecholamines

The anoretic effect of corticotropin -releasing factor (CRF) was not dependent on adrenal activation in goldfish (Carassius auratus). Moreover, an interaction between CRF and the hypothalamic catecholaminergic system in the central regulation of food intake was observed. The intracerebroventricular (icv) administration of CRF increased cortisol levels and reduced food intake and hypothalamic norepinephrine and dopamine content at 2 hr postinjection, with these effects reversed by a-helical CRF[9_41] pretreatment. The anoretic effect of CRF was independent of the circulating cortisol increase, because it was only evoked after icv injections but not after intraperitoneal (ip) administration. Furthermore, the increase in plasma cortisol levels induced by ip administration of this steroid did not modify feeding.

Food intake inhibition by melatonin in goldfish (Carassius auratus).

Feeding regulation by monoamines, neuropeptides and certain hormones has been studied in fish, but a possible role of melatonin is unknown. The purpose of the present study was to investigate the effects of melatonin on food intake in goldfish. Fishes were housed in 12L:12D and injected with different doses of either melatonin or 2-iodomelatonin. Two routes of administration, intracerebroventricular and intraperitoneal injections, and two times of the daily photocycle, midday and midnight, were tested. Food intake was measured at 2, 5 and 8 h postinjection. Melatonin and its analog, 2-iodomelatonin intracerebroventricularly injected had no effect on food intake at any time. However, intraperitoneal injections of both indoleamines significantly reduced food intake at different postinjection times. The inhibitory effect of melatonin was blocked by intraperitoneal administration of its antagonist, luzindole. These results demonstrate the in vivo efficiency of luzindole as melatonin antagonist, and thus provide a useful experimental tool to investigate melatonin functions. In conclusion, both melatonin and its agonist 2-iodomelatonin administered peripherally, inhibit food intake in goldfish, and this inhibitory effect appears to be mediated via luzindole-sensitive melatonin receptors. Our results strongly suggest that melatonin is involved in the peripheral satiety mechanisms in goldfish.

Melatonin reduces body weight in goldfish (Carassius auratus): effects on metabolic resources and some feeding regulators.

Abstract:  The objective of the present study was to analyze the effects of chronic melatonin (10 μg/g body weight) on body weight and the main energetic reserves, particularly hepatic and muscle content of proteins, lipids and glycogen in goldfish. In addition, we studied plasma leptin and ghrelin, and hypothalamic content of neuropeptide Y (NPY) and monoamines after chronic melatonin treatment in order to elucidate a possible interplay between melatonin and these feeding regulators on the body weight regulation in this species. Body weight gain and specific growth rate were reduced (74% and 76%, respectively) after chronic (10 days) intraperitoneal (i.p.) treatment with melatonin. The carbohydrate and lipid metabolism was regulated by melatonin in goldfish, because this indoleamine reduced muscle glycogen stores and increased lipid mobilization. A suppressive trend, but not statistically significant, in circulating ghrelin was observed after chronic treatment with melatonin. Chronic melatonin administration significantly reduced noradrenergic metabolism and increased dihydroxiphenylacetic acid content in the hypothalamus, without significant modifications in the serotoninergic system. Thus, it could be suggested that melatonin may mediate its action on energy balance in fish, at least in part, via interactions with hypothalamic catecholaminergic system. Plasma leptin and hypothalamic NPY remained unaltered after melatonin treatment, suggesting that these feeding regulators may not be involved in the effects of melatonin on energy homeostasis in fish.

Differential VIP and VIP1 receptor gene expression in rat thymocyte subsets

Nervous, endocrine, and immune systems share a large number of regulatory molecules including hormones and neuropeptides. Vasoactive intestinal peptide (VIP) plays an important role in a variety of immunological functions. In the present report, we sorted purified thymocytes of the four major thymic subsets defined by CD4 and CD8 phenotypes. We demonstrate by reverse transcription (RT) and polymerase chain reaction (PCR) both VIP and VIP1 receptor gene expression in double positive (CD4+CD8+) and single positive (CD4+CD8-, CD4-CD8+) thymocyte subsets. Double negative thymocytes (CD4-CD8-) lack VIP and VIP1 receptor gene expression.

α1-Adrenergic and dopaminergic receptors are involved in the anoretic effect of corticotropin-releasing factor in goldfish

This study investigates the noradrenergic and/or dopaminergic receptors subtypes involved in the anoretic action of CRF in goldfish. Agonists and antagonists of alpha1- and alpha2-adrenoceptors, and D1- and D2-dopaminergic receptors were intracerebroventricularly (i.c.v.) administered alone or in combination with CRF in the case of antagonists. Food intake and hypothalamic content of catecholamines and their metabolites were measured at 2 h postinjection. On one hand, alpha1-adrenergic receptor antagonist, but not alpha2, blocked the anoretic effect of CRF. Moreover, we found a blockade of CRF-induced anoretic action by pretreatment with specific D1- and D2-dopaminergic antagonists. On the other hand, the i.c.v. administration of CRF reduced hypothalamic norepinephrine (NE) and dopamine (DA) content, without modifications in their metabolism. Thus, our results suggest that the anoretic effect of CRF appears to be mediated by alpha1-adrenergic and dopaminergic receptors in fish. Second, the reduction in hypothalamic NE and DA synthesis could be due to a direct effect of CRF treatment and/or a secondary effect of food intake reduction.