Fatty acids of different nature differentially modulate feed intake in rainbow trout

Feed intake is subjected to a complex regulation involving a plethora of signals, among which nutrients stand as one of the most important. In mammals, the gastrointestinal tract is able to sense nutrients in the lumen, and respond with the release of signaling molecules that ultimately modulate brain circuits governing appetite, resulting in decreased/increased feeding. Whether equivalent mechanisms operate in fish remains unknown. In a recent study, we described that the gastrointestinal tract of rainbow trout contains several sensors for free fatty acids (FAs), and that the luminal presence of FAs of different length and degree of unsaturation modulates the levels of key gastrointestinal hormones involved in feed intake regulation. In this study, our aim was to characterize the impact of such a luminal presence of FAs on brain appetite-regulatory centers, as well as its effects on rainbow trout feed intake. Major results from this study demonstrated that: (i) FAs of different length and degree of unsaturation [medium-chain (MCFAs, octanoate), long-chain (LCFAs, oleate), long-chain polyunsaturated (PUFA, α-linolenate), and short-chain (SCFA, butyrate) FAs] differentially modulate feed intake levels when administered intragastrically, (ii) intragastrically-administered FAs modulate the phosphorylation status of appetite-related transcription factors, as well as mRNA levels of key appetite-regulating neuropeptides, in the hypothalamus and/or telencephalon, (iii) luminal presence of FAs results in changes in the central abundance of mRNAs encoding gastrointestinal hormone receptors, and (vi) luminal FA-derived central changes in neuropeptide mRNAs are not observed (or are lessened) in vagotomized fish. Together, these results provide comprehensive evidence in favor of a gut-brain axis in fish. In addition, we observed different responses in terms of feed intake regulation depending on the type of fatty acid administered into the lumen, which is very relevant for aquaculture considering differences in fatty acid composition in aquafeedsAgencia Estatal de Investigación | Ref. PID2019-103969RB-C31Agencia Estatal de Investigación | Ref. IJC2019-039166-IMinisterio de Universidades | Ref. FPU19/00122Ministerio de Educación, Cultura y Deporte | Ref. FPU16/0004

Impact of feeding diets with enhanced vegetable protein content and presence of umami taste-stimulating additive on gastrointestinal amino acid sensing and feed intake regulation in rainbow trout

The regulation of feed intake in fish is dependent upon different neuroendocrine and metabolic mechanisms including amino acid sensing in the gastrointestinal tract (GIT). However, there is little information regarding the impact of diets on such mechanisms. Therefore, in this study, we fed rainbow trout (Oncorhynchus mykiss) with 3 diets: a diet with high content of fishmeal and low content of soybean protein concentrate (SPC) (HF), a diet with a reduced content of fishmeal and high content of SPC (LF), and the LF diet supplemented with an umami tastestimulating additive (LFU). Fish were fed ad libitum once a day for 4 weeks, with no significant differences being registered in feed intake among groups. At the end of the feeding trial, we collected samples of different areas of the GIT (stomach, proximal and distal intestine) and hypothalamus at different times: after 48 h of fasting (time 0), and 1 h, 4 h, and 24 h after feeding. We evaluated the activity of pepsin in the stomach and trypsin and chymotrypsin in the proximal intestine, as well as mRNA abundance of transcripts encoding amino acid transporters and taste receptors, intracellular signalling molecules, and hormones. Moreover, we assessed the hypothalamic mRNA abundance of neuropeptides involved in feed intake regulation. Feeding rainbow trout with LF did not result in marked alterations in parameters related to digestive function and amino acid sensing in the rainbow trout GIT, nor in the expression of gastrointestinal hormones (except cck) and hypothalamic neuropeptides. In contrast, supplementation of the LF diet with an umami taste-stimulating additive resulted in a general improvement of digestive or absorptive function (increased protein, dry matter and energy digestibility, and earlier peak in plasma amino acid levels) and activation of gut-brain axis mechanisms involved in feed intake regulation through the transcriptional activation of amino acid transporters, taste receptors, signalling molecules, and hormones. These results demonstrate that the dietary inclusion of umami receptor stimulants has the potential to improve fish physiological responses to the rise in levels of vegetable protein in the diet.Xunta de Galicia | Ref. GPC-ED431B 2022/01Ministerio de Universidades | Ref. FPU19/00122Agencia Estatal de Investigación | Ref. IJC2019-039166-IUniversidade de Vigo/CISU

Fatty acid sensing in the gastrointestinal tract of rainbow trout: different to mammalian model?

It is well established in mammals that the gastrointestinal tract (GIT) senses the luminal presence of nutrients and responds to such information by releasing signaling molecules that ultimately regulate feeding. However, gut nutrient sensing mechanisms are poorly known in fish. This research characterized fatty acid (FA) sensing mechanisms in the GIT of a fish species with great interest in aquaculture: the rainbow trout (Oncorhynchus mykiss). Main results showed that: (i) the trout GIT has mRNAs encoding numerous key FA transporters characterized in mammals (FA transporter CD36 -FAT/CD36-, FA transport protein 4 -FATP4-, and monocarboxylate transporter isoform-1 -MCT-1-) and receptors (several free FA receptor -Ffar- isoforms, and G protein-coupled receptors 84 and 119 -Gpr84 and Gpr119-), and (ii) intragastrically-administered FAs differing in their length and degree of unsaturation (i.e., medium-chain (octanoate), long-chain (oleate), long-chain polyunsaturated (α-linolenate), and short-chain (butyrate) FAs) exert a differential modulation of the gastrointestinal abundance of mRNAs encoding the identified transporters and receptors and intracellular signaling elements, as well as gastrointestinal appetite-regulatory hormone mRNAs and proteins. Together, results from this study offer the first set of evidence supporting the existence of FA sensing mechanisms n the fish GIT. Additionally, we detected several differences in FA sensing mechanisms of rainbow trout vs. mammals, which may suggest evolutionary divergence between fish and mammals.Xunta de Galicia | Ref. ED431B 2022/01Agencia Estatal de Investigación española | Ref. PID2019-103969RB-C31Ministerio de Educación, Cultura y Deporte | Ref. FPU19/00122Ministerio de Educación, Cultura y Deporte | Ref. FPU16/00045Ministerio de Ciencia e Innovación | Ref. IJC2019-039166-

A Ciencia Cierta: proyecto de visibilización

[RESUMEN] ¿Por qué no aprendemos en las escuelas los grandes logros que miles de mujeres han alcanzado para el avance de la humanidad? El currículum escolar, especialmente el formal, no refleja las conquistas y éxitos que las mujeres han conseguido a lo largo de la Historia. Su escasa presencia en los libros de texto, fundamentalmente en el campo de la Ciencia y de la Tecnología, genera una idea errónea, sesgada y parcial de quiénes fueron los protagonistas de los hechos y procesos históricos, científicos y tecnológicos más importantes para el desarrollo y el progreso de nuestra sociedad. Esta identificación del hombre como protagonista histórico, principalmente en estos campos, podría estar provocando una feminización y una masculinización de las carreras académicas y profesionales, propiciada desde la infancia por un orden simbólico minuciosamente establecido en el que impera la dominación masculina. La aplicación por tanto de la perspectiva de género en los contenidos escolares y en el propio currículum oculto, nos permite equilibrar las relaciones desiguales de poder y desbancar al androcentrismo del puesto privilegiado que la autoridad masculina le ha otorgado. En este texto se presenta un proyecto de investigación que pretende por un lado devolver a las mujeres pioneras, científicas y tecnólogas el espacio que les corresponde dentro de las escuelas y por tanto dentro del conocimiento global. Y por otro, visibilizar nuevos modelos femeninos referenciales para transformar las subjetividades individuales que se edifican con fuerza en la infancia y en la adolescencia

Nuevas tendencias en el derecho de la competencia y de la propiedad industrial

Divulgação dos SUMÁRIOS das obras recentemente incorporadas ao acervo da Biblioteca Ministro Oscar Saraiva do STJ. Em respeito à Lei de Direitos Autorais, não disponibilizamos a obra na íntegra.Localização na estante: 347.77 N964tOrganizado por: Anxo Tato Plaza, Julio Costas Comesaña, Pablo I. Fernández Carballo-Calero, Francisco J. Torres Pérez e Sara Louredo Casad

Hyaluronic acid hydrogels reinforced with laser spun bioactive glass micro- and nanofibres doped with lithium

The repair of articular cartilage lesions in weight-bearing joints remains as a significant challenge due to the low regenerative capacity of this tissue. Hydrogels are candidates to repair lesions as they have similar properties to cartilage extracellular matrix but they are unable to meet the mechanical and biological requirements for a successful outcome. Here, we reinforce hyaluronic acid (HA) hydrogels with 13-93-lithium bioactive glass micro- and nanofibres produced by laser spinning. The glass fibres are a reinforcement filler and a platform for the delivery of therapeutic lithium-ions. The elastic modulus of the composites is more than three times higher than in HA hydrogels. Modelling of the reinforcement corroborates the experimental results. ATDC5 chondrogenic cells seeded on the composites are viable and more proliferation occurs on the hydrogels containing fibres than in HA hydrogels alone. Furthermore, the chondrogenic behavior on HA constructs with fibres containing lithium is more marked than in hydrogels with no-lithium fibres.Xunta de Galicia | Ref. ED431B 2016/042Xunta de Galicia | Ref. POS-A/2013/161Xunta de Galicia | Ref. ED481D 2017/010Xunta de Galicia | Ref. ED481B 2016/047-

Caracterización de mecanismos sensores de aminoácidos y cuerpos cetónicos en peces. Implicación en el control de la ingesta de alimento.

La ingesta de alimento es un proceso regulado por diversos factores. A nivel central, concretamente en el hipotálamo, se integran diferentes señales nerviosas, endocrinas y metabólicas para regular la ingesta. Con respecto a las señales metabólicas, se ha demostrado que diferentes cantidades de determinados nutrientes en la dieta influyen aumentando o disminuyendo la ingesta. En el hipotálamo existen diferentes mecanismos sensores de los niveles de nutrientes circulantes, que al activarse modulan la expresión de neuropéptidos orexigénicos y anorexigénicos, los cuales actúan aumentado o disminuyendo la ingesta, respectivamente. En este aspecto, en peces ya se han caracterizado a nivel central mecanismos sensores de glucosa y ácidos grasos, pero se desconoce la existencia sensores de aminoácidos o cuerpos cetónicos. Al igual que para los otros nutrientes principales, el incremento en los niveles de aminoácidos específicos como la leucina inhibe la ingesta en mamíferos. Este proceso ocurre a través de la activación de sistemas sensores de aminoácidos mediados por la activación de mTOR y/o inhibición de la vía de señalización de AMPK, o vía la activación del metabolismo de aminoácidos ramificados. Además, la deficiencia de aminoácidos esenciales provoca un incremento en la ingesta a través de los sistemas sensores de aminoácidos mediante el control de GCN2 y eIF2α. En peces, no se ha estudiado todavía la presencia ni el funcionamiento de posibles sistemas sensores de aminoácidos comparables, ni su relación con el control de la ingesta. Su presencia en áreas centrales que regulan la ingesta es razonable, considerando que la mayoría de los peces son carnívoros, y por lo tanto son fuertemente dependientes (realmente mucho más que los mamíferos omnívoros en los cuales se han realizado la mayoría de los estudios hasta la fecha) de dietas con proteína/aminoácidos. Los únicos estudios disponibles en peces demuestran en tejidos periféricos como musculo e hígado los efectos de los cambios de aminoácidos en la abundancia de mRNA de mTOR. Por otro lado, un incremento en los niveles de cuerpo cetónicos estimula la ingesta. Hasta la fecha solamente se han postulado algunos posibles mecanismos sensores en mamíferos, pero todavía no han sido caracterizados. Por este motivo, el objetivo principal de esta tesis será caracterizar los posibles mecanismos sensores de aminoácidos y cuerpos cetónicos y su relación con la ingesta utilizando trucha arcoíris (Oncorhynchus mykiss) como modelo de pez teleósteo.A inxesta de alimento é un proceso regulado por diversos factores. A nivel central, concretamente no hipotálamo, intégranse diferentes sinais nerviosos, endocrinos e metabólicos para regular a inxesta. Con respecto aos sinais metabólicos, demostrouse que diferentes cantidades de determinados nutrintes na dieta inflúen aumentando ou diminuíndo a inxesta. No hipotálamo existen diferentes mecanismos sensores dos niveis de nutrintes circulantes, que ao activarse modulan a expresión de neuropéptidos orexixénicos e anorexixénicos, os cales actúan aumentando ou diminuíndo a inxesta, respectivamente. Neste aspecto, en peixes caracterizáronse a nivel central mecanismos sensores de glucosa e ácidos grasos, pero descoñécese a existencia de sensores de aminoácidos e corpos cetónicos. Ao igual que para os outros nutrintes principais, o incremento nos niveis de aminoácidos específicos como a leucina inhiben a inxesta en mamíferos. Este proceso ocorre a través da activación de sistemas sensores de aminoácidos mediados pola activación de mTOR e/ou inhibición da vía de sinalización de AMPK, ou a vía de activación do metabolismo de aminoácidos ramificados. Ademais, a deficiencia de aminoácidos esenciais provoca un incremento na inxesta a través dos sistemas sensores de aminoácidos mediante o control de GCN2 e eIF2α. Nos peixes, non se estudiaron aínda a presencia nin o funcionamento de posibles sistemas sensores de aminoácidos comparables, nin a súa relación con control da inxesta. A súa presencia en áreas centrais que regulan a inxesta é razonable, considerando que a maioría dos peixes son carnívoros, e polo tanto son fortemente dependentes (moito máis que os mamíferos omnívoros nos que se realizaron a maioría dos estudos ata a data) de dietas con proteína/aminoácidos. Os únicos estudos dispoñibles en peixes demostran en tecidos periféricos como músculo e fígado os efectos dos cambios de aminoácidos na abundancia de mRNA de mTOR. Por outro lado, un incremento dos niveis de corpos cetónicos estimulan a inxesta. Ata a data soamente postuláronse algún posibles mecanismo sensores en mamíferos, pero todavía non foron caracterizados. Por este motivo, o obxectivo principal da tese será caracterizar os posibles mecanismos sensores de aminoácidos e corpos cetónicos e a súa relación coa inxesta utilizando a troita arco da vella (Oncorhynchus mykiss) como modelo de peixe teleósteo.Food intake is a process regulated by several factors. At central level, in hypothalamus, different nervous signals, endocrine and metabolic are integrated in order to regulate food intake. Regarding metabolic signals, it has been demonstrated that different amounts of determinate nutrients increase or decrease food intake. In hypothalamus there are different nutrient sensing systems, which, when they are activated, modulate the expression of orexigenic and anorexigenic neuropeptides, respectively. In fish it has been characterized at central level sensors of glucose and fatty acids, but it is unknown the presence of amino acid or ketone bodies sensors. As for other nutrients, the increase in levels of specific amino acids such as leucine, inhibit food intake in mammals. This process occurs through activation of amino acid sensing systems mediated by activation of mTOR and/or inhibition of signaling pathway of AMPK, or by activation of metabolism of branched-chain amino acid. Moreover, deficiency of essential amino acid triggers an increase in food intake through systems mediated by control of GCN2 and eIF2α. In fish, it has not been studied the presence and functioning of putative amino acid sensing systems, nor the relation with the control of food intake. Its presence in central areas which regulate food intake is reasonable, considering that most of fish are carnivorous, and strongly dependent (much more than omnivorous mammals in which most studied has been made) of diets with protein/amino acids. Available studies in fish only demonstrated in peripheral tissues such as muscle or liver effects of changes in amino acids in mRNA abundance of mTOR. On the other side, an increase in levels of ketone bodies stimulate food intake. In mammals some possible mechanisms have been postulated, however in has not been characterized until now. For this reason, the aim of this thesis is characterize possible amino acids and ketone bodies sensing systems and their relation with food intake using rainbow trout (Oncorhynchus mykiss) as model of teleost fish.Ministerio de Economía y Competitividad | Ref. AGL2016‐74857‐C3‐1‐RMinisterio de Ciencia e Innovación | Ref. PID2019-103969RB-C3Xunta de Galicia | Ref. ED431B 2019/3

Oral and pre-absorptive sensing of amino acids relates to hypothalamic control of food intake in rainbow trout

To assess the putative role of taste and pre-absorptive sensing of amino acids in food intake control in fish, we carried out an oral administration with L-leucine, L-valine, L-proline or L-glutamic acid in rainbow trout (Oncorhynchus mykiss). Treatment with proline significantly reduced voluntary food intake at 2h and 3h after oral administration, while glutamic acid showed a less pronounced satiating effect at 3h. The mRNA expression of taste receptor subunits tas1r1, tas1r2a, tas1r2b, and tas1r3 was measured in the epithelium overlying the bony basyhyal of the fish (analogous to the tetrapod tongue) at 10, 20 or 30 min following treatment. No significant changes were observed, except for a tas1r down-regulation by valine at 30 mins. Of the downstream taste signalling genes that were analysed in parallel, plcb2 and possibly trpm5 (non-significant trend) were down-regulated 20 min after proline and glutamic acid treatment. The signal originated in the oropharyngeal and/or gastric cavity presumably relays to the brain since changes in genes involved in the regulation of food intake occurred in hypothalamus 10-30 min after oral treatment with amino acids. In particular, proline induced changes consistent with an increased anorexigenic potential in the hypothalamus. We have therefore demonstrated, for the first time in fish, that the peripheral (pre-absorptive) detection of an amino acid (L-proline), presumably by taste-related mechanisms, elicits a satiety signal that in hypothalamus is translated into changes in cellular signalling and neuropeptides regulating food intake, ultimately resulting in decreased food intake.Ministerio de Educación, Cultura y Deporte | Ref. FPU16/00045Xunta de Galicia | Ref. ED431B 2019/37Xunta de Galicia | Ref. ED481B2018/01

Leucine sensing in rainbow trout hypothalamus is direct but separate from mTOR signalling in the regulation of food intake

In prior studies, we evidenced the presence in fish hypothalamus of different systems sensing changes in leucine levels to relate them to food intake control. To assess whether or not those effects are due to a direct action of leucine, we evaluated in the present in vitro study if rainbow trout (Oncorhynchus mykiss) hypothalamus respond to changes in leucine levels in a way comparable to that observed in vivo. Thus, we incubated hypothalamus in vitro with increased leucine concentrations (1, 5 and 25 mM). Then, we evaluated parameters related to mechanisms of amino acid sensing as well as transcription factors, and neuropeptides. Amino acid sensing systems related to metabolism of BCAA and glutamine and GCN2 kinase are activated by the presence of leucine, in a way comparable to that observed in vivo thus supporting a direct action of leucine on them. However, the activation of these systems did not trigger mTOR signalling pathway including downstream protein targets of mTOR, transcription factors, and mRNA abundance of neuropeptides involved in food intake the regulation of food intake. Therefore, the activation of hypothalamic mTOR observed after leucine administration in vivo is not a direct response to leucine but indirect. The absence in vitro of connections between hypothalamus and other brain areas and/or the lack of changes in levels of hormones, particularly insulin, could be responsible of this differential response.Financiado para publicación en acceso aberto: Universidade de Vigo/CISUGXunta de Galicia | Ref. ED431B 2019/37Agencia Estatal de Investigación | Ref. PID2019-103969RB-C31Ministerio de Educación, Cultura y Deporte (España) | Ref. FPU16/0004

Feeding stimulation ability and central effects of intraperitoneal treatment of L-leucine, L-valine, and L-proline on amino acid sensing systems in rainbow trout: implication in food intake control

To continue gathering knowledge on the central regulation of food intake in response to amino acids in teleost fish, using as a model rainbow trout (Oncorhynchus mykiss), we evaluated in a first experiment the feeding attractiveness of L-leucine, L-valine, and L-proline offered as an agar gel matrix. In a second experiment, we assessed the effect of intraperitoneal (IP) treatment with the same amino acids on food intake. In a third experiment, we carried out a similar IP administration of amino acids to evaluate the response of amino acid sensing mechanisms in the hypothalamus and telencephalon. Results are discussed in conjunction with an earlier study where leucine and valine were administered intracerebroventricularly (ICV). The attractiveness of amino acids does not appear to relate to their effects on food intake, at least when administrated by-passing ingestion and luminal absorption, since two attractive amino acids resulted in an anorexigenic (Leu) or no effects (Pro) on food intake while a non-attractive amino acid (Val) induced anorexigenic (IP treatment) or orexigenic (ICV treatment) responses. The effects of Leu on food intake might relate to the expression of hypothalamic neuropeptides and result from the direct activation of amino acid sensing systems. In contrast, while valine had few effects on hypothalamic amino acid sensing systems after ICV treatment, a significant amount of parameters become affected by IP treatment suggesting that the effect of Val after IP treatment is indirect. Proline had no relevant effects on amino acid sensing systems, neuropeptide expression, and food intake, which suggest that this amino acid might not have a relevant role in the homeostatic regulation of food intake through hypothalamic mechanisms. In telencephalon, the same amino acid sensing systems operating in hypothalamus appear to be present and respond to Leu and Val, but it is still unclear how they might relate to the control of food intake.Ministerio de Educación, Cultura y Deporte | Ref. FPU16/00045Agencia Estatal de Investigación | Ref. AGL2016-74857-C3-1-RAgencia Estatal de Investigación | Ref. IJCI-2016-3049