Papel dos mecanismos sensores de ácidos grasos na regulación da inxesta de alimento en troita arco da vella como modelo de peixe teleósteo : control endocrino e mecanismos intracelulares implicados

Feed is the major cost of aquaculture, and further increases in situations in which the fish eat less due to stress produced by aquaculture practices. The fact that a fish eat or not eat depends on the integratory role of a number of both central and peripheral mechanisms of various types (metabolism, circadian, nervous and endocrine), whose operation is in turn a reflection of different processes involved in aquaculture interactions which only partly have been elucidated to date. A metabolic level, research in recent years in the research group with a model of teleost fish of interest in aquaculture such as rainbow trout has demonstrated that food intake is modulated in response to changes in circulating glucose levels and certain fatty acids, which are detected by sensing mechanism located at central and peripheral level. Regarding sensing mechanisms of fatty acids, we have obtained evidence for the presence in hypothalamus, liver and endocrine pancreas of three fatty acid sensing mechanisms based on: i) the metabolism of fatty acids, ii) Binding to transporter FAT/CD36 and subsequent modulation of transcription factors and iii) inhibition of the K+ATPchannel. These systems are activated in response to increased levels of long chain (oleate) or medium chain (octanoate) fatty acids by triggering changes in the production of hypothalamic orexigenic and anorexigenic factors. Changes in these factors result in inhibition of the food intake, which was more importantly after octanoate action, in contrast to mammals in which medium-chain fatty acids are not involved in the metabolic control of food intake. There is no information about metabolic integration of sensor systems in fish in response to changes in the levels of more than one nutrient. We do not knownthe possible existence of common intracellular signaling pathways involving AMPK and sirtuins and different intracellular messengers involved in the transmission of the sensor information. Therefore, the objectives of this project will deepen the characterization and function of fatty acid sensing mechanisms in fish and their relation to the control of food intake, specifically: - To determine the potential modulatory effect of insulin, leptin, GLP-1, ghrelin and CCK on the activity of fatty acid sensing systems, neuropeptide production and food intake by IP, ICV and in vitro treatments. Where and the effect is observed, we will evaluate its specificity with receptor antagonists. -To study the role of ceramide as an intermediary between the activation/inhibition of sensor systems and the expression of neuropeptides that regulate food intake. To this end, we will assess inin vivo and in vitro studieschanges in the levels of ceramides in the sensing areas in conditions of activation/inhibition of sensor systems. If a response is observed, we will study in vitro the effect of ceramides on the expression of hypothalamic neuropeptides. -To evaluate the response of the sensor systems of fatty acids against increases in circulating fatty acids when what varies is the carbohydrate content in the diet. -To determine the presence at central and peripheral locations of parameters related to the integration of metabolic information provided by sensor systems as well as intracellular pathways involved in intracellular signaling. We will assess changes in the amount of AMPK and sirtuins in experimental situations that stimulate/inhibit nutrient sensor systems. In those situations where we find a possible relationship, we will see if AMPK inhibition alters responsiveness. Finally, we will also determine the intracellular signaling pathways involved characterizing the presence and response of S6K1, Akt, and TORC1.

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