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ASSESSING DIAGNOSTIC and THERAPEUTIC TARGETS in OBESITY- ASSOCIATED LIVER DISEASES Noemí Cabré Casares

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ASSESSING DIAGNOSTIC and THERAPEUTIC TARGETS in OBESITY- ASSOCIATED LIVER DISEASES Noemí Cabré Casares ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY- ASSOCIATED LIVER DISEASES Noemí Cabré Casares ADVERTIMENT. L'accés als continguts d'aquesta tesi doctoral i la seva utilització ha de respectar els drets de la persona autora. Pot ser utilitzada per a consulta o estudi personal, així com en activitats o materials d'investigació i docència en els termes establerts a l'art. 32 del Text Refós de la Llei de Propietat Intel·lectual (RDL 1/1996). Per altres utilitzacions es requereix l'autorització prèvia i expressa de la persona autora. En qualsevol cas, en la utilització dels seus continguts caldrà indicar de forma clara el nom i cognoms de la persona autora i el títol de la tesi doctoral. No s'autoritza la seva reproducció o altres formes d'explotació efectuades amb finalitats de lucre ni la seva comunicació pública des d'un lloc aliè al servei TDX. Tampoc s'autoritza la presentació del seu contingut en una finestra o marc aliè a TDX (framing). Aquesta reserva de drets afecta tant als continguts de la tesi com als seus resums i índexs. ADVERTENCIA. El acceso a los contenidos de esta tesis doctoral y su utilización debe respetar los derechos de la persona autora. Puede ser utilizada para consulta o estudio personal, así como en actividades o materiales de investigación y docencia en los términos establecidos en el art. 32 del Texto Refundido de la Ley de Propiedad Intelectual (RDL 1/1996). Para otros usos se requiere la autorización previa y expresa de la persona autora. En cualquier caso, en la utilización de sus contenidos se deberá indicar de forma clara el nombre y apellidos de la persona autora y el título de la tesis doctoral. No se autoriza su reproducción u otras formas de explotación efectuadas con fines lucrativos ni su comunicación pública desde un sitio ajeno al servicio TDR. Tampoco se autoriza la presentación de su contenido en una ventana o marco ajeno a TDR (framing). Esta reserva de derechos afecta tanto al contenido de la tesis como a sus resúmenes e índices. WARNING. Access to the contents of this doctoral thesis and its use must respect the rights of the author. It can be used for reference or private study, as well as research and learning activities or materials in the terms established by the 32nd article of the Spanish Consolidated Copyright Act (RDL 1/1996). Express and previous authorization of the author is required for any other uses. In any case, when using its content, full name of the author and title of the thesis must be clearly indicated. Reproduction or other forms of for profit use or public communication from outside TDX service is not allowed. Presentation of its content in a window or frame external to TDX (framing) is not authorized either. These rights affect both the content of the thesis and its abstracts and indexes. UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares Assessing Diagnostic and Therapeutic Targets in Obesity-Associated Liver Diseases Noemí Cabré Casares Doctoral Dissertation, 2019 1 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 2 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 3 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 4 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares Noemí Cabré Casares Assessing Diagnostic and Therapeutic Targets in Obesity- Associated Liver Diseases Doctoral Dissertation Supervised by Dr. Jorge Joven Maried Department of Medicine and Surgery Reus 2019 5 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 6 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares FACULTAT DE MEDICINA I CIÈNCIES DE LA SALUT DEPARTAMENT DE MEDICINA Y CIRUGIA Carrer Sant Llorenç, 21 43201 Reus Tel. 977 759 306 Fax. 977 759352 TO WHOM IT MAY CONCERN I STATE that the present study, entitled “Assessing Diagnostic and Therapeutic Targets in Obesity- Associated Liver Diseases”, presented by Noemí Cabré Casares with the purpose of obtaining the degree of Doctor, has been carried out under my supervision at the Department of Medicine and Surgery of this University. Reus, 1th June 2019 Doctoral Thesis Supervisor Prof. Jorge Joven Maried 7 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 8 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares “Be the best you can be. Today the competition is fierce, the funds are tight, and the only way you can do something is by being extremely good at what you do.” Elizabeth Neufeld, PhD Originally appeared in Albert and Mary Lasker Foundation 9 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 10 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares A la meva família, 11 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 12 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares Acknowledgements 13 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares 14 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares En primer lloc m’agradaria agrair el suport a totes aquelles persones que, en major o menor mesura, m’han acompanyat durant aquesta apassionant aventura. Cada granet de sorra ha estat imprescindible per a què, finalment, aquest manuscrit hagi agafat forma i, a hores d’ara se’l pugui anomenar la “tesi”. Al Prof. Joven, el meu mentor, la primera persona que va veure “quelcom” en mi el mateix dia que ens vam conèixer, ara fa 8 anys... Durant tot aquest temps s’ha esforçat en inculcar-me una sèrie de valors resumits en frases com: “net i polit”, “no te fíes ni de tu padre”, “has entès aquesta lliçó?”, “les coses s’han de fer bé a la primera”... que amb el pas dels anys he après a valorar i entendre millor. Gràcies per la seva paciència i per haver-me donat l’oportunitat de créixer en aquest món tan sacrificat com és el de la ciència. Al Dr. Camps, sempre disposat a ajudar-nos. Sóc incapaç de comptar la quantitat d’hores que has passat amb mi ajudant-me a elaborar el que avui és el fruit de tant de temps invertit en mi. Moltes gràcies pel teu suport incondicional. M’has animat a seguir endavant amb tota la força i il·lusió possibles, tot i les dificultats que hem anat trobant pel camí, que no han estat poques. Al Dr. Durán, todavía recuerdo el primer día que leí su nombre, y la consecuente insistencia para conseguir contactar con él. No habría imaginado que poco después formara parte de esta aventura siendo un referente indiscutible tanto en el ámbito conceptual como profesional. Muchas gracias por la sabiduría que me ha transmitido. Al Dr. Vendrell i la Dra. Fernández, i en general a tots els membres del DIAMET, pels consells rebuts i l’ajuda prestada, però sobretot per l’oportunitat de participar i defensar el treball del dia a dia en aquelles tardes de dimecres. Hem viscut molt bons moments junts. Al Prof. Domingo i al Dr. Nadal, gràcies per l’oportunitat de deixar-me endinsar en el món dels elements traça i guiar-nos durant aquests anys. Al Salva i la Anna, els post-docs del grup, heu estat un dels pilars fonamentals durant aquesta etapa. Tinc molt present els dies amb el “Salvi al Cuelpo” i les inacabables classes de metabolòmica...quina aventura! No podré agrair-vos suficientment, en especial a l’Anna, tota la dedicació emprada en mi mentre era la seva “nena de pràctiques”. Moltes gràcies als dos. Al Gerard i la Eli, les noves generacions. Sabeu que confio en vosaltres i estic convençuda que heu après a ser crítics a l’hora de prendre decisions. Sé que la vostra aventura té molt de recorregut per endavant i que la portareu a terme amb il·lusió i energia. Moltes gràcies per totes aquelles tardes de riures, plors i, com no, de reflexions intentant idealitzar un món millor. 15 UNIVERSITAT ROVIRA I VIRGILI ASSESSING DIAGNOSTIC AND THERAPEUTIC TARGETS IN OBESITY-ASSOCIATED LIVER DISEASES Noemí Cabré Casares Als meus alumnes, els meus nens, heu aconseguit que aquests anys no tan sols hagi descobert la meva passió per la ciència sinó també per la docència. M’enorgulleixo recordant la vostra evolució del primer dia al últim. No us podeu imaginar quin canvi! A tots els que han format part de la meva aventura americana, Dr. Vondriska, Manuel, Doug, Max and Yuki. First, Dr. Vodnriska, I greatly appreciate the opportunity you gave me to join your team as member of your lab. Thank you very much for teaching and guiding me during these 3 months. Doug, my mentor of bioinformatics, and the best student in Catalan culture I have ever seen. Thank you for everything. Manuel, mi guía incondicional incluso meses antes de que cruzara el charco. Gracias por tu apoyo y asesoramiento, aunque sea desde la distancia, sé que siempre estás disponible para solucionar todos “mis pequeños y no tan pequeños desastres”. A la Fedra, la meva siamesa, companya de feina i amiga.
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