Hypothalamic Integration of Metabolic, Endocrine, and Circadian Signals in Fish: Involvement in the Control of Food Intake

The regulation of food intake in fish is a complex process carried out through several different mechanisms in the central nervous system (CNS) with hypothalamus being the main regulatory center. As in mammals, a complex hypothalamic circuit including two populations of neurons: one co-expressing neuropeptide Y (NPY) and Agouti-related peptide (AgRP) and the second one population co-expressing pro-opiomelanocortin (POMC) and cocaine- and amphetamine-regulated transcript (CART) is involved in the integration of information relating to food intake control. The production and release of these peptides control food intake, and the production results from the integration of information of different nature such as levels of nutrients and hormones as well as circadian signals. The present review summarizes the knowledge and recent findings about the presence and functioning of these mechanisms in fish and their differences vs. the known mammalian model

Difusión de los diarios en Euskalherria desde la transición política. De lo ordinal (datos) a lo cardinal (referentes)

El presente artículo consta de dos partes bien definidas. En la primera parte, los autores analizan los datos de la evolución de la difusión de la prensa en Euskalherria desde el inicio de la transición política (1976) hasta fechas recientes (1998) y su relación con los procesos de vertebración territorial y de interrelación cultural y política. A tal fin, dirigen una doble mirada: de un lado, hacia la difusión de la prensa de ámbito estatal y la de la prensa propia de Euskadi y Nafarroa; de otro, hacia la relación entre las diversas prensas de información general dentro de Euskadi, de Nafarroa y entre ambas. En la segunda parte, conscientes de que la difusión es un asunto de cifras pero también -y no en menor medida- de referentes, esbozan algunas líneas de trabajo acerca de la construcción del referente en la prensa presente en Euskalherria. No en vano, los proyectos de vertebración territorial e interrelación cultural y política promovidos por los diarios no sólo se concretan en estrategias más o menos complejas sino también a través de manifestaciones cotidianas tales como las que en el artículo se comentan: la representación territorial de los mapas del tiempo, la denominación de las secciones y la crónica de una fiesta como la de San Fermín

Amino Acid Carriers of the Solute Carrier Families 7 (SLC7) and 38 (SLC38) Are Involved in Leucine Sensing in the Brain of Atlantic Salmon (Salmo salar)

Sensing of amino acids in fish brain, especially branched-chain amino acids (BCAA) like leucine, is involved in regulation of feed intake through different mechanisms. However, there is limited information regarding the possible involvement of mechanisms dependent on amino acid carriers of the solute carrier families (SLC) known to be key regulators of intracellular leucine concentration, namely L-type amino acid transporter 1 (LAT1), and sodium-dependent neutral amino acid transporter 2 (SNAT2) and 9,(SNAT9), for which evidence of their participation is available in mammals. Comparative analysis amongst sequences revealed a complex pattern of paralogues in Atlantic salmon, for LAT1 (slc7a5aa, slc7a5ab, slc7a5ba, slc7a5bb, slc7a5ca, and slc7a5cb), SNAT2 (slc38a2a and slc38a2b) and SNAT9 (slc38a9). After establishing phylogenetic relationships of the different paralogues evaluated, samples of the selected brain areas were taken from Atlantic salmon to assess tissue distribution of transcripts. In an additional experiment, fish were fed two diets with different levels of leucine (high leucine: 35 g/kg vs. control leucine: 27.3 g/kg). The high leucine diet resulted in lower feed intake and increased mRNA abundance of specific paralogues of LAT1 (slc7a5aa, slc7a5ab, and slc7a5bb) and SNAT2 (slc38a2a and slc38a2b) though apparently not for SNAT9 in brain areas like hypothalamus and telencephalon involved in food intake regulation. The results obtained suggest a role for members of the SLC family in the anorectic effect of leucine and thus their involvement as additional amino acid sensing mechanism not characterised so far in fish regulation of feed intake.publishedVersio

Stress Effects on the Mechanisms Regulating Appetite in Teleost Fish

The homeostatic regulation of food intake relies on a complex network involving peripheral and central signals that are integrated in the hypothalamus which in turn responds with the release of orexigenic or anorexigenic neuropeptides that eventually promote or inhibit appetite. Under stress conditions, the mechanisms that control food intake in fish are deregulated and the appetite signals in the brain do not operate as in control conditions resulting in changes in the expression of the appetite-related neuropeptides and usually a decreased food intake. The effect of stress on the mechanisms that regulate food intake in fish seems to be mediated in part by the corticotropin-releasing factor (CRF), an anorexigenic neuropeptide involved in the activation of the HPI axis during the physiological stress response. Furthermore, the melanocortin system is also involved in the connection between the HPI axis and the central control of appetite. The dopaminergic and serotonergic systems are activated during the stress response and they have also been related to the control of food intake. In addition, the central and peripheral mechanisms that mediate nutrient sensing capacity and hence implicated in the metabolic control of appetite are inhibited in fish under stress conditions. Finally, stress also affects peripheral endocrine signals such as leptin. In the present minireview, we summarize the knowledge achieved in recent years regarding the interaction of stress with the different mechanisms that regulate food intake in fish

Hypothalamic AMPKα2 regulates liver energy metabolism in rainbow trout through vagal innervation

Hypothalamic AMPK plays a major role in the regulation of whole body metabolism and energy balance. Present evidence has demonstrated that this canonical mechanism is evolutionarily conserved. Thus, recent data demonstrated that inhibition of AMPKα2 in fish hypothalamus led to decreased food intake and liver capacity to use and synthesize glucose, lipids, and amino acids. We hypothesize that a signal of abundance of nutrients from the hypothalamus controls hepatic metabolism. The vagus nerve is the most important link between the brain and the liver. We therefore examined in the present study whether surgical transection of the vagus nerve in rainbow trout is sufficient to alter the effect in liver of central inhibition of AMPKα2. Thus, we vagotomized (VGX) or not (Sham) rainbow trout and then intracerebroventricularly administered adenoviral vectors tagged with green fluorescent protein alone or linked to a dominant negative isoform of AMPKα2. The inhibition of AMPKα2 led to reduced food intake in parallel with changes in the mRNA abundance of hypothalamic neuropeptides [neuropeptide Y ( npy), agouti-related protein 1 ( agrp1), and cocaine- and amphetamine-related transcript ( cartpt)] involved in food intake regulation. Central inhibition of AMPKα2 resulted in the liver having decreased capacity to use and synthesize glucose, lipids, and amino acids. Notably, these effects mostly disappeared in VGX fish. These results support the idea that autonomic nervous system actions mediate the actions of hypothalamic AMPKα2 on liver metabolism. Importantly, this evidence indicates that the well-established role of hypothalamic AMPK in energy balance is a canonical evolutionarily preserved mechanism that is also present in the fish lineage

Oral administration of melatonin counteracts several of the effects of chronic stress in rainbow trout

To assess a possible antistress role of melatonin in fish, we orally administered melatonin to rainbow trout for 10 d and then kept the fish under normal or high stocking density conditions during the last 4 d. Food intake; biochemical parameters in plasma (cortisol, glucose, and lactate concentrations); liver (glucose and glycogen concentrations, and glycogen synthase activity); enzyme activities of amylase, lipase, and protease in foregut and midgut; and content of the hypothalamic neurotransmitters dopamine and serotonin, as well as their oxidized metabolites, 3,4-dihydroxyphenylacetic acid and 5-hydroxy-3-indoleacetic acid, were evaluated under those conditions. High stocking density conditions alone induced changes indicative of stress conditions in plasma cortisol concentrations, liver glycogenolytic potential, the activities of some digestive enzymes, and the 3,4-dihydroxyphenylacetic acid-to-dopamine and 5-hydroxy-3-indoleacetic acid-to-serotonin ratios in the hypothalamus. Melatonin treatment in nonstressed fish induced an increase in liver glycogenolytic potential, increased the activity of some digestive enzymes, and enhanced serotoninergic and dopaminergic metabolism in hypothalamus. The presence of melatonin in stressed fish resulted in a significant interaction with cortisol concentrations in plasma, glycogen content, and glycogen synthase activity in liver and dopaminergic and serotoninergic metabolism in the hypothalamus. In general, the presence of melatonin mitigated several of the effects induced by stress, supporting an antistress role for melatonin in rainbow trout.Ministerio de Ciencia e Innovación | Ref. AGL2010-22247-C03-03Xunta de Galicia | Ref. CN2012/ 00

Sensing Glucose in the Central Melanocortin Circuits of Rainbow Trout: A Morphological Study

In mammals, glucosensing markers reside in brain areas known to play an important role in the control of food intake. The best characterized glucosensing mechanism is that dependent on glucokinase (GK) whose activation by increased levels of glucose leads in specific hypothalamic neurons to decreased or increased activity, ultimately leading to decreased food intake. In fish, evidence obtained in recent years suggested the presence of GK-like immunoreactive cells in different brain areas related to food intake control. However, it has not been established yet whether or not those neuronal populations having glucosensing capacity are the same that express the neuropeptides involved in the metabolic control of food intake. Therefore, we assessed through dual fluorescent in situ hybridization the possible expression of GK in the melanocortinergic neurons expressing proopiomelanocortin (POMC) or agouti-related protein (AGRP). POMC and AGRP expression localized exclusively in the rostral hypothalamus, in the ventral pole of the lateral tuberal nucleus, the homolog of the mammalian arcuate nucleus. Hypothalamic GK expression confined to the ependymal cells coating the ventral pole of the third ventricle but some expression level occurred in the AGRP neurons. GK expression seems to be absent in the hypothalamic POMC neurons. These results suggest that AGRP neurons might sense glucose directly through a mechanism involving GK. In contrast, POMC neurons would not directly respond to glucose through GK and would require presynaptic inputs to sense glucose. Ependymal cells could play a critical role relying glucose metabolic information to the central circuitry regulating food intake in fish, especially in POMC neurons