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Role of Carnitine Palmitoyltransferase 1A As a Downstream Effector of Ghrelin in Cortical Neurons and Hypothalamus

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Role of Carnitine Palmitoyltransferase 1A As a Downstream Effector of Ghrelin in Cortical Neurons and Hypothalamus Role of carnitine palmitoyltransferase 1A as a downstream effector of ghrelin in cortical neurons and hypothalamus Joan Francesc Mir Bonnín ADVERTIMENT . La consulta d’aquesta tesi queda condicionada a l’acceptació de les següents condicions d'ús: La difusió d’aquesta tesi per mitjà del servei TDX ( www.tdx.cat ) i a través del Dipòsit Digital de la UB ( diposit.ub.edu ) ha estat autoritzada pels titulars dels drets de propietat intel·lectual únicament per a usos privats emmarcats en activitats d’investigació i docència. No s’autoritza la seva reproducció amb finalitats de lucre ni la seva difusió i posada a disposici ó des d’un lloc aliè al servei TDX ni al Dipòsit Digital de la UB . No s’autoritza la presenta ció del seu contingut en una finestra o marc aliè a TDX o al Dipòsit Digital de la UB (framing). Aquesta reserva de drets afecta tant al resum de presentació de la tesi com als seus continguts. En la utilització o cita de parts de la tesi és obligat indica r el nom de la persona autora. ADVERTENCIA . La consulta de esta tesis queda condicionada a la aceptación de las siguientes condiciones de uso: La difusión de esta tesis por medio del servicio TDR ( www.tdx.cat ) y a través del Repositorio Digital de la UB ( diposit.ub.edu ) ha sido autorizada por los titulares de los derechos de propiedad intelectual únicamente para usos privados enmarcados en actividades de investigación y docencia. No se autoriza su reproducción con finalidades de lucro ni su difusión y pue sta a disposición desde un sitio ajeno al servicio TDR o al Repositorio Digital de la UB . No se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR o al Repositorio Digital de la UB (framing). Esta reserva de derechos afecta tanto al resumen de presentación de la tesis como a sus contenidos. En la utilización o cita de partes de la tesis es obligado indicar el nombre de la persona autora. WARNING . On having consulted this thesis you’re accepting the following use conditions: Spre ading this thesis by the TDX ( www.tdx.cat ) service and by the UB Digital Repository ( diposit.ub.edu ) has been authorized by the titular of the intellectual property rights only for private uses placed in investigation and teaching activities. Reproduction with lucrative aims is not authorized n or its spreading and availability from a site foreign to the TDX service or to the UB Digital Repository . Introducing its content in a window or frame foreign to the TDX service or to the UB Digital Repository is not authorized (framing). Tho s e rights affect to the presentation summary of the thesis as well as to its contents. In the using or citation of parts of the thesis it’s obliged to indicate the name of the author. Departament de Bioquímica i Fisiologia Facultat de Farmàcia Role of carnitine palmitoyltransferase 1A as a downstream effector of ghrelin in cortical neurons and hypothalamus Joan Francesc Mir Bonnín 2016 - 2 - FACULTAT DE FARMÀCIA Programa de doctorat en Biotecnologia Role of carnitine palmitoyltransferase 1A as a downstream effector of ghrelin in cortical neurons and hypothalamus Memòria presentada per Joan Francesc Mir Bonnín per optar al títol de Doctor per la Universitat de Barcelona. Aquesta tesi s’ha realitzat sota la direcció de la Dra. Dolors Serra Cucurull i el Dr. Fausto García Hegardt, en la Secció de Bioquímica i Biologia Molecular, del Departament de Bioquímica i Fisiologia de la Facultat de Farmàcia de la Universitat de Barcelona. Dra. Dolors Serra Cucurull Dr. Fausto García Hegardt Joan Francesc Mir Barcelona, 2016 - 3 - - 4 - A en Pep i na Joana, perquè sempre he intentat que poguessin estar orgullosos del seu fill A Alejandro, porque tiene suficiente paciencia para ver en mí cosas buenas “Ciencia es todo aquello sobre lo cual siempre cabe discusión.” José Ortega y Gasset - 5 - - 6 - AGRAÏMENTS En primera instància voldria agrair als meus directors de tesi la oportunitat que m’han brindat de fer la tesi en el nostre grup. Per una banda, em cal agrair a la Dra. Dolors Serra la paciència i els consells que m’ha anat donant a diari des que vaig trepitjar per primera vegada aquest laboratori, ja fa uns anys. Sempre se m’ha presentat com una persona de la que se’n pot aprendre cada dia i que en la seva implicació sempre ha anat un pas per endavant. D’altra banda, he d’agrair al Dr. Fausto García Hegardt la oportunitat que se’m va donar primer d’entrar al grup com a estudiant de llicenciatura i després en la obtenció del finançament per fer la tesi, sense el qual aquesta aventura no hagués començat. A part dels meus directors, he d’agrair a la Dra. Laura Herrero la seva capacitat de transmetre el seu entusiasme per la recerca i les seves ganes de millorar cada dia. També he de d’agrair a la Dra. Guillermina Asins els seus consells i les seves contagioses ganes de viure, i que a més em van atreure a jo per primera vegada al món de la recerca. Després he d’agrair moltíssim a la Dra. Paula Mera les hores que va invertir en ensenyar-me moltes de les tècniques que he emprat a la tesi. A més d’esser una persona de la que val la pena aprendre científicament, ha estat una immillorable companya i amiga que vam enyorar molt quan va marxar del lab. D’altra banda, he d’agrair al Dr. Pep Orellana, el Dr. Kamil Makowski i la Dra. Mida Malandrino, per tots els bons moments que vam passar al laboratori i a fora del laboratori, durant els primers anys que vaig tenir al laboratori. A més voldria donar les gràcies a Mar Arasa per haver compartit durant els primers anys i el màster moltes hores de poiata. També voldria agrair a la futura Dra. Minéia Weber, perquè encara no n’és conscient de com l’estic enyorant i com l’enyoraré després de totes les aventures i desventures que hem passat plegats compartint aquests anys de la tesi. A la Dra. María Calderón- Domínguez i la Dra. Raquel Fucho els hi he de donar gràcies perquè m’han ensenyat que tan important és tenir bon criteri científic com tenir bon criteri per a la vida en general. M’ho he passat molt bé amb vosaltres, nines i vos enyoraré molt. Esper que ens tornem a trobar en el futur. A més he d’agrair moltíssim a la Dra. Cristina Suñol i al Dr. Matthieu Lichtenstein, per haver tengut ganes d’ajudar-me amb la recerca de la tesi. Especialment a en Matthieu per haver-me ensenyat les tècniques que han permès fer gran part dels experiments amb els cultius primaris corticals. En el mateix sentit, voldria agrair a la Dra. Josefina Casas i la Dra. Gemma Fabriàs per la imprescindible ajuda que ens han donat per l’anàlisi lipidòmica del MBH i també a la Dra. Antònia Ribes i la Dra. Judit Garcia per l’inestimable ajuda que ens han donat per l’anàlisi dels intermediaris del cicle de Krebs. Certament sense aquestes anàlisis el plantejament dels resultats de la tesi serien diferents. També he d’agrair a la Dra. Núria Casals i a tothom del seu laboratori de la Universitat Internacional de Catalunya per les discussions de resultats que fèiem gairebé setmanalment per la valuable ajuda que m’ha suposat durant la tesi, especialment a la Dra. Sara Ramírez, la Dra. Macarena Pozo i la Dra. Rosalía Rodríguez. - 7 - D’altra banda voldria donar gràcies a na Nina Steiner, en Fran García, na Blanca Balañá, en Jordi Capdevila i na Sandra Recalde als que esper no haver fet embolicar massa la troca mentre els ajudava amb els seus projectes. També voldria agrair a tota la resta de persones que han passat pel lab, pels moments que hem passat plegats que t’enriqueixen d’una manera o una altra, especialment a Anna Orozco, Alessandra Piccoli, Natascia Caroccia, Eduviges Bustos, Iván Paz, Éilis Sutton, Júlia Vallvé, Lorea Valcárcel, la Dra. Sofia Costa, el Dr. David Santos, la Dra. Mar Romero i el Dr. Martín Alcalá-Díaz. Esper no haver-me deixat ningú, perquè no m’ho podria perdonar, ja que durant tots aquests anys han passat moltes persones que d’una manera o una altra han estat importants en el dia a dia. Després voldria agrair especialment la paciència que han tengut amb jo 3 persones especialment. D’una banda, mon pare i ma mare, en Pep i na Joana, que sempre han estat a l’aguait dels èxits i dels fracassos dels seus fills i que han perdonat la comunicació poc freqüent amb el seu fill. Esper poder-vos- ho compensar qualque dia. D’altra banda he d’agrair especialment al meu company d’aventures i riures per tot el temps i la serenor que m’ha anat dedicant aquests anys. Alejandro, gràcies per haver-me sabut dur a bon port. T’estim i passi el que passi sempre t’estimaré. Moltes gràcies! - 8 - ABSTRACT Role of carnitine palmitoyltransferase 1A as a downstream effector of ghrelin in cortical neurons and hypothalamus Previous studies have reported the importance of carnitine palmitoyltransferase (CPT) 1A as an essential part of downstream ghrelin signaling in the central nervous system (CNS) for the control of food intake. Lipid metabolism in the ventromedial hypothalamus (VMH) has emerged as a crucial pathway in the regulation of feeding and energy homeostasis. However, the relationship between changes in CPT1A activity and the intracellular downstream effectors in the VMH that contribute to appetite modulation is not fully understood, nor its possible involvement in central extra-hypothalamic functions of ghrelin.
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