{"id":{"repo_id":"cadiz","oai_identifier":"oai:rodin.uca.es:10498/29467"},"canonical_url":"https://search.dev.ndltd.org/etd/cadiz/oai:rodin.uca.es:10498/29467","repository":{"repo_id":"cadiz","name":"Universidad de Cadiz","base_url":"https://rodin.uca.es/oai/request"},"display":{"title":"Study of Erythroid Antioxidant Depletion in Childhood Obesity","abstract":"Obesity and overweight currently affects one third of children worldwide, and approximately 60% of cases present concomitant metabolic alterations that could trigger future complications. Among these alterations, insulin resistance has been identified as a forerunner state in the onset of characteristic metabolic disorders behind childhood obesity and its comorbidities. In this respect, it is widely recognized that both inflammation and oxidative stress play a central role in the development of these complications. However, the molecular mechanisms behind these pathogenic events remain unclear. The main aim of this Doctoral Thesis is to elucidate the molecular mechanisms involved in the inactivation of antioxidant defenses in childhood obesity and its comorbidities, in order to facilitate the search for new therapeutic targets. To this end, we recruited a sample of children and adolescents with obesity, with and without insulin resistance, as well as normal-weight healthy controls. From all these participants, plasma and erythrocyte samples were collected and subjected to complementary molecular biology and omics determinations (i.e., metallomics, metabolomics) with the aim of comprehensively characterizing the biochemical and molecular perturbations underlying the characteristic pathogenic events behind childhood obesity and metabolic syndrome. Furthermore, the study population was stratified based on different criteria, including sex, pubertal stage, and insulin secretion profile, to investigate the involvement of these potential risk/susceptibility factors in childhood obesity-related oxidative dysfunction. The application of molecular biology techniques evidenced that oxidative stress occurring in childhood obesity and metabolic syndrome may have a multifactorial origin, comprising alterations related to a decreased capacity to generate reducing power through the pentose phosphate pathway, catalase post-translational modifications, and exacerbated oxidase activity. These results were largely reflected at the metallomics level, since study subjects with obesity had decreased blood levels of essential elements involved in the antioxidant defense and metabolic control (e.g., selenium, manganese, zinc, iron) and increased levels of potentially deleterious species (e.g., copper). Finally, preliminary metabolomics results corroborate the above, showing how childhood obesity is accompanied by profound metabolic dysregulations, including failures in antioxidant systems (e.g., glutathione metabolism, generation of oxidation/nitrosylation products of nucleic acid, proteins, and lipids), various pathways related to energy metabolism (e.g., glycolysis, pentose phosphate pathway, lipid ß-oxidation, tricarboxylic acid cycle), homeostasis of amino acids (particularly branched-chain and aromatic amino acids), steroid hormones, and phospholipids, as well as other alterations related to the gut microbiota and environmental exposure factors (e.g., diet). In this vein, it should be noted that this complex set of intertwined biochemical and molecular disturbances was generally sharpened among subjects who presented concomitant insulin resistance to childhood obesity, highlighting the need of implementing personalized therapeutic tools depending on the presence/absence of metabolic complications. Furthermore, many of these disorders were found to be deeply influenced by a myriad of factors such as sex, pubertal stage, and the pattern of insulin secretion of the study subjects, thereby pinpointing the importance of addressing this interindividual variability as potential risk factors contributing to the susceptibility of developing obesity-associated complications at early ages. In summary, this Doctoral Thesis has demonstrated that childhood obesity accompanied by metabolic syndrome is characterized by profound alterations in oxidative metabolism, which in turn are affected by a wide range of individual factors (e.g., sex, pubertal stage, insulin secretion profile) and involve a number of closely interrelated molecular mechanisms.","abstract_html":"Obesity and overweight currently affects one third of children worldwide, and approximately 60% of cases present concomitant metabolic alterations that could trigger future complications. Among these alterations, insulin resistance has been identified as a forerunner state in the onset of characteristic metabolic disorders behind childhood obesity and its comorbidities. In this respect, it is widely recognized that both inflammation and oxidative stress play a central role in the development of these complications. However, the molecular mechanisms behind these pathogenic events remain unclear. The main aim of this Doctoral Thesis is to elucidate the molecular mechanisms involved in the inactivation of antioxidant defenses in childhood obesity and its comorbidities, in order to facilitate the search for new therapeutic targets. To this end, we recruited a sample of children and adolescents with obesity, with and without insulin resistance, as well as normal-weight healthy controls. From all these participants, plasma and erythrocyte samples were collected and subjected to complementary molecular biology and omics determinations (i.e., metallomics, metabolomics) with the aim of comprehensively characterizing the biochemical and molecular perturbations underlying the characteristic pathogenic events behind childhood obesity and metabolic syndrome. Furthermore, the study population was stratified based on different criteria, including sex, pubertal stage, and insulin secretion profile, to investigate the involvement of these potential risk/susceptibility factors in childhood obesity-related oxidative dysfunction. The application of molecular biology techniques evidenced that oxidative stress occurring in childhood obesity and metabolic syndrome may have a multifactorial origin, comprising alterations related to a decreased capacity to generate reducing power through the pentose phosphate pathway, catalase post-translational modifications, and exacerbated oxidase activity. These results were largely reflected at the metallomics level, since study subjects with obesity had decreased blood levels of essential elements involved in the antioxidant defense and metabolic control (e.g., selenium, manganese, zinc, iron) and increased levels of potentially deleterious species (e.g., copper). Finally, preliminary metabolomics results corroborate the above, showing how childhood obesity is accompanied by profound metabolic dysregulations, including failures in antioxidant systems (e.g., glutathione metabolism, generation of oxidation/nitrosylation products of nucleic acid, proteins, and lipids), various pathways related to energy metabolism (e.g., glycolysis, pentose phosphate pathway, lipid ß-oxidation, tricarboxylic acid cycle), homeostasis of amino acids (particularly branched-chain and aromatic amino acids), steroid hormones, and phospholipids, as well as other alterations related to the gut microbiota and environmental exposure factors (e.g., diet). In this vein, it should be noted that this complex set of intertwined biochemical and molecular disturbances was generally sharpened among subjects who presented concomitant insulin resistance to childhood obesity, highlighting the need of implementing personalized therapeutic tools depending on the presence/absence of metabolic complications. Furthermore, many of these disorders were found to be deeply influenced by a myriad of factors such as sex, pubertal stage, and the pattern of insulin secretion of the study subjects, thereby pinpointing the importance of addressing this interindividual variability as potential risk factors contributing to the susceptibility of developing obesity-associated complications at early ages. In summary, this Doctoral Thesis has demonstrated that childhood obesity accompanied by metabolic syndrome is characterized by profound alterations in oxidative metabolism, which in turn are affected by a wide range of individual factors (e.g., sex, pubertal stage, insulin secretion profile) and involve a number of closely interrelated molecular mechanisms.","abstract_has_math":false,"creators":["González Domínguez, Álvaro"],"institution":null,"degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":[],"advisors":["Lechuga Sancho, Alfonso María","Mateos Bernal, Rosa María","García Cózar, Francisco José"],"committee_chairs":[],"committee_members":[],"year":2023,"date_issued":"2023","date_published":"2023","updated_at":"2026-07-24T01:29:47Z","subjects":["childhood obesity","Metabolic Syndrome","oxidative stress","Obesidad infantil","Síndrome metabólico","Estrés oxidativo"],"languages":["eng"],"rights":["Attribution-NonCommercial-NoDerivatives 4.0 Internacional"],"rights_urls":["http://creativecommons.org/licenses/by-nc-nd/4.0/"],"identifier_entries":[]},"links":{"outbound_url":"http://hdl.handle.net/10498/29467","outbound_label":"Handle","outbound_source":"dc:identifier.uri"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor.advisor","label":"Advisor","values":["Lechuga Sancho, Alfonso María","Mateos Bernal, Rosa María","García Cózar, Francisco José"]},{"key":"dc:contributor.other","label":"Dc Contributor Other","values":["Biomedicina, Biotecnología y Salud Pública","Materno-Infantil y Radiología"]},{"key":"dc:creator","label":"Author","values":["González Domínguez, Álvaro"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:date.accessioned","label":"Dc Date Accessioned","values":["2023-10-24T11:11:35Z"]},{"key":"dc:date.available","label":"Dc Date Available","values":["2023-10-24T11:11:35Z"]},{"key":"dc:date.issued","label":"Date","values":["2023"]},{"key":"dc:type","label":"Dc Type","values":["doctoral thesis"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["childhood obesity","Metabolic Syndrome","oxidative stress","Obesidad infantil","Síndrome metabólico","Estrés oxidativo"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language.iso","label":"Language (ISO)","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["Attribution-NonCommercial-NoDerivatives 4.0 Internacional"]},{"key":"dc:rights.uri","label":"Rights URI","values":["http://creativecommons.org/licenses/by-nc-nd/4.0/"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier.uri","label":"Identifier URI","values":["http://hdl.handle.net/10498/29467"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description.abstract","label":"Abstract","values":["Obesity and overweight currently affects one third of children worldwide, and approximately 60% of cases present concomitant metabolic alterations that could trigger future complications. Among these alterations, insulin resistance has been identified as a forerunner state in the onset of characteristic metabolic disorders behind childhood obesity and its comorbidities. In this respect, it is widely recognized that both inflammation and oxidative stress play a central role in the development of these complications. However, the molecular mechanisms behind these pathogenic events remain unclear. The main aim of this Doctoral Thesis is to elucidate the molecular mechanisms involved in the inactivation of antioxidant defenses in childhood obesity and its comorbidities, in order to facilitate the search for new therapeutic targets. To this end, we recruited a sample of children and adolescents with obesity, with and without insulin resistance, as well as normal-weight healthy controls. From all these participants, plasma and erythrocyte samples were collected and subjected to complementary molecular biology and omics determinations (i.e., metallomics, metabolomics) with the aim of comprehensively characterizing the biochemical and molecular perturbations underlying the characteristic pathogenic events behind childhood obesity and metabolic syndrome. Furthermore, the study population was stratified based on different criteria, including sex, pubertal stage, and insulin secretion profile, to investigate the involvement of these potential risk/susceptibility factors in childhood obesity-related oxidative dysfunction. The application of molecular biology techniques evidenced that oxidative stress occurring in childhood obesity and metabolic syndrome may have a multifactorial origin, comprising alterations related to a decreased capacity to generate reducing power through the pentose phosphate pathway, catalase post-translational modifications, and exacerbated oxidase activity. These results were largely reflected at the metallomics level, since study subjects with obesity had decreased blood levels of essential elements involved in the antioxidant defense and metabolic control (e.g., selenium, manganese, zinc, iron) and increased levels of potentially deleterious species (e.g., copper). Finally, preliminary metabolomics results corroborate the above, showing how childhood obesity is accompanied by profound metabolic dysregulations, including failures in antioxidant systems (e.g., glutathione metabolism, generation of oxidation/nitrosylation products of nucleic acid, proteins, and lipids), various pathways related to energy metabolism (e.g., glycolysis, pentose phosphate pathway, lipid ß-oxidation, tricarboxylic acid cycle), homeostasis of amino acids (particularly branched-chain and aromatic amino acids), steroid hormones, and phospholipids, as well as other alterations related to the gut microbiota and environmental exposure factors (e.g., diet). In this vein, it should be noted that this complex set of intertwined biochemical and molecular disturbances was generally sharpened among subjects who presented concomitant insulin resistance to childhood obesity, highlighting the need of implementing personalized therapeutic tools depending on the presence/absence of metabolic complications. Furthermore, many of these disorders were found to be deeply influenced by a myriad of factors such as sex, pubertal stage, and the pattern of insulin secretion of the study subjects, thereby pinpointing the importance of addressing this interindividual variability as potential risk factors contributing to the susceptibility of developing obesity-associated complications at early ages. In summary, this Doctoral Thesis has demonstrated that childhood obesity accompanied by metabolic syndrome is characterized by profound alterations in oxidative metabolism, which in turn are affected by a wide range of individual factors (e.g., sex, pubertal stage, insulin secretion profile) and involve a number of closely interrelated molecular mechanisms.","El sobrepeso y la obesidad afectan actualmente a un tercio de la población infantil mundial, y aproximadamente el 60% de los casos presentan alteraciones metabólicas concomitantes que podrían desencadenar futuras complicaciones. Entre estas alteraciones, la resistencia a la insulina se ha identificado como un estado precursor en la aparición de las perturbaciones metabólicas características de la obesidad infantil y sus comorbilidades. En este sentido, es ampliamente reconocido que tanto la inflamación como el estrés oxidativo juegan un papel central en el desarrollo de estas complicaciones. Sin embargo, los mecanismos moleculares detrás de estos eventos patogénicos siguen sin ser totalmente esclarecidos. El objetivo principal de esta Tesis Doctoral es dilucidar los mecanismos moleculares implicados en la inactivación de las defensas antioxidantes en la obesidad infantil y sus comorbilidades, con el fin de así facilitar la búsqueda de nuevas dianas terapéuticas. Para este propósito, reclutamos una población observacional de niños y adolescentes con obesidad, con y sin resistencia a la insulina, así como controles sanos normopeso. De todos estos participantes, se recolectaron muestras de plasma y eritrocitos, las cuales se sometieron a determinaciones ómicas (i.e., metalómica, metabolómica) y de biología molecular complementarias con el objetivo de caracterizar de manera integral las perturbaciones bioquímicas y moleculares que pueden ser la base de estos eventos patogénicos característicos de la obesidad infantil y el síndrome metabólico. Asimismo, la población de estudio se estratificó en base a distintos criterios, incluyendo el sexo, estadio puberal y afecciones en la secreción de insulina, para así investigar la implicación de estos posibles factores de riesgo/susceptibilidad en el deterioro oxidativo relacionado con la obesidad infantil. La aplicación de técnicas de biología molecular evidenció que el estrés oxidativo que se observa en la obesidad infantil y el síndrome metabólico puede tener un origen multifactorial, comprendiendo alteraciones relacionadas con una capacidad disminuida de generar poder reductor a través de la ruta de las pentosas fosfato, modificaciones postraduccionales de la catalasa, y actividad oxidasa exacerbada. Estos resultados se vieron en gran medida reflejados a nivel metalómico, ya que los sujetos de estudio con obesidad presentaron niveles sanguíneos disminuidos de elementos esenciales involucrados en la defensa antioxidante y el control metabólico (e.g., selenio, manganeso, zinc, hierro) y niveles aumentados de especies potencialmente perjudiciales (e.g., cobre). Por último, resultados metabolómicos preliminares corroboran que la obesidad infantil se ve acompañada de una profunda desregulación metabólica, incluyendo fallos en sistemas antioxidantes (e.g., metabolismo del glutatión, generación de productos de oxidación/nitrosilación de ácidos nucleicos, proteínas y lípidos), diversas rutas relacionadas con el metabolismo energético (e.g., glicólisis, ruta de las pentosas fosfato, β-oxidación de lípidos, ciclo de los ácidos tricarboxílicos), la homeostasis de los aminoácidos (en particular aminoácidos de cadena ramificada y aromáticos), las hormonas esteroideas y los fosfolípidos, así como otras alteraciones relacionadas con la microbiota intestinal y factores de exposición ambiental (e.g., dieta). Cabe señalar que este conjunto de complejas perturbaciones bioquímicas y moleculares se vieron por lo general acentuadas entre aquellos sujetos que presentaron resistencia insulínica concomitante a la obesidad infantil, lo que pone de manifiesto la necesidad de implementar herramientas terapéuticas personalizadas en función de la presencia/ausencia de complicaciones metabólicas. Asimismo, encontramos que gran parte de estos trastornos se ven profundamente influenciados por una miríada de factores como el sexo, el estadio puberal y el patrón de secreción de insulina de los sujetos de estudio, lo que subraya la importancia de abordar esta variabilidad interindividual como posible factor de riesgo que contribuye a la susceptibilidad de desarrollar complicaciones asociadas a la obesidad en edad temprana. En conclusión, esta Tesis Doctoral ha permitido demostrar que la obesidad infantil acompañada de síndrome metabólico se caracteriza por profundas alteraciones del metabolismo oxidativo, el cual se ve afectado por una amplia gama de factores individuales (e.g., sexo, estadio puberal, patrón de secreción de insulina) y en el que intervienen diversos mecanismos moleculares estrechamente interrelacionados."]},{"key":"dc:format","label":"Dc Format","values":["application/pdf"]},{"key":"dc:title","label":"Title","values":["Study of Erythroid Antioxidant Depletion in Childhood Obesity"]}]}],"canonical_facts":{"dc:contributor.advisor":["Lechuga Sancho, Alfonso María","Mateos Bernal, Rosa María","García Cózar, Francisco José"],"dc:contributor.other":["Biomedicina, Biotecnología y Salud Pública","Materno-Infantil y Radiología"],"dc:creator":["González Domínguez, Álvaro"],"dc:date.accessioned":["2023-10-24T11:11:35Z"],"dc:date.available":["2023-10-24T11:11:35Z"],"dc:date.issued":["2023"],"dc:description.abstract":["Obesity and overweight currently affects one third of children worldwide, and approximately 60% of cases present concomitant metabolic alterations that could trigger future complications. Among these alterations, insulin resistance has been identified as a forerunner state in the onset of characteristic metabolic disorders behind childhood obesity and its comorbidities. In this respect, it is widely recognized that both inflammation and oxidative stress play a central role in the development of these complications. However, the molecular mechanisms behind these pathogenic events remain unclear. The main aim of this Doctoral Thesis is to elucidate the molecular mechanisms involved in the inactivation of antioxidant defenses in childhood obesity and its comorbidities, in order to facilitate the search for new therapeutic targets. To this end, we recruited a sample of children and adolescents with obesity, with and without insulin resistance, as well as normal-weight healthy controls. From all these participants, plasma and erythrocyte samples were collected and subjected to complementary molecular biology and omics determinations (i.e., metallomics, metabolomics) with the aim of comprehensively characterizing the biochemical and molecular perturbations underlying the characteristic pathogenic events behind childhood obesity and metabolic syndrome. Furthermore, the study population was stratified based on different criteria, including sex, pubertal stage, and insulin secretion profile, to investigate the involvement of these potential risk/susceptibility factors in childhood obesity-related oxidative dysfunction. The application of molecular biology techniques evidenced that oxidative stress occurring in childhood obesity and metabolic syndrome may have a multifactorial origin, comprising alterations related to a decreased capacity to generate reducing power through the pentose phosphate pathway, catalase post-translational modifications, and exacerbated oxidase activity. These results were largely reflected at the metallomics level, since study subjects with obesity had decreased blood levels of essential elements involved in the antioxidant defense and metabolic control (e.g., selenium, manganese, zinc, iron) and increased levels of potentially deleterious species (e.g., copper). Finally, preliminary metabolomics results corroborate the above, showing how childhood obesity is accompanied by profound metabolic dysregulations, including failures in antioxidant systems (e.g., glutathione metabolism, generation of oxidation/nitrosylation products of nucleic acid, proteins, and lipids), various pathways related to energy metabolism (e.g., glycolysis, pentose phosphate pathway, lipid ß-oxidation, tricarboxylic acid cycle), homeostasis of amino acids (particularly branched-chain and aromatic amino acids), steroid hormones, and phospholipids, as well as other alterations related to the gut microbiota and environmental exposure factors (e.g., diet). In this vein, it should be noted that this complex set of intertwined biochemical and molecular disturbances was generally sharpened among subjects who presented concomitant insulin resistance to childhood obesity, highlighting the need of implementing personalized therapeutic tools depending on the presence/absence of metabolic complications. Furthermore, many of these disorders were found to be deeply influenced by a myriad of factors such as sex, pubertal stage, and the pattern of insulin secretion of the study subjects, thereby pinpointing the importance of addressing this interindividual variability as potential risk factors contributing to the susceptibility of developing obesity-associated complications at early ages. In summary, this Doctoral Thesis has demonstrated that childhood obesity accompanied by metabolic syndrome is characterized by profound alterations in oxidative metabolism, which in turn are affected by a wide range of individual factors (e.g., sex, pubertal stage, insulin secretion profile) and involve a number of closely interrelated molecular mechanisms.","El sobrepeso y la obesidad afectan actualmente a un tercio de la población infantil mundial, y aproximadamente el 60% de los casos presentan alteraciones metabólicas concomitantes que podrían desencadenar futuras complicaciones. Entre estas alteraciones, la resistencia a la insulina se ha identificado como un estado precursor en la aparición de las perturbaciones metabólicas características de la obesidad infantil y sus comorbilidades. En este sentido, es ampliamente reconocido que tanto la inflamación como el estrés oxidativo juegan un papel central en el desarrollo de estas complicaciones. Sin embargo, los mecanismos moleculares detrás de estos eventos patogénicos siguen sin ser totalmente esclarecidos. El objetivo principal de esta Tesis Doctoral es dilucidar los mecanismos moleculares implicados en la inactivación de las defensas antioxidantes en la obesidad infantil y sus comorbilidades, con el fin de así facilitar la búsqueda de nuevas dianas terapéuticas. Para este propósito, reclutamos una población observacional de niños y adolescentes con obesidad, con y sin resistencia a la insulina, así como controles sanos normopeso. De todos estos participantes, se recolectaron muestras de plasma y eritrocitos, las cuales se sometieron a determinaciones ómicas (i.e., metalómica, metabolómica) y de biología molecular complementarias con el objetivo de caracterizar de manera integral las perturbaciones bioquímicas y moleculares que pueden ser la base de estos eventos patogénicos característicos de la obesidad infantil y el síndrome metabólico. Asimismo, la población de estudio se estratificó en base a distintos criterios, incluyendo el sexo, estadio puberal y afecciones en la secreción de insulina, para así investigar la implicación de estos posibles factores de riesgo/susceptibilidad en el deterioro oxidativo relacionado con la obesidad infantil. La aplicación de técnicas de biología molecular evidenció que el estrés oxidativo que se observa en la obesidad infantil y el síndrome metabólico puede tener un origen multifactorial, comprendiendo alteraciones relacionadas con una capacidad disminuida de generar poder reductor a través de la ruta de las pentosas fosfato, modificaciones postraduccionales de la catalasa, y actividad oxidasa exacerbada. Estos resultados se vieron en gran medida reflejados a nivel metalómico, ya que los sujetos de estudio con obesidad presentaron niveles sanguíneos disminuidos de elementos esenciales involucrados en la defensa antioxidante y el control metabólico (e.g., selenio, manganeso, zinc, hierro) y niveles aumentados de especies potencialmente perjudiciales (e.g., cobre). Por último, resultados metabolómicos preliminares corroboran que la obesidad infantil se ve acompañada de una profunda desregulación metabólica, incluyendo fallos en sistemas antioxidantes (e.g., metabolismo del glutatión, generación de productos de oxidación/nitrosilación de ácidos nucleicos, proteínas y lípidos), diversas rutas relacionadas con el metabolismo energético (e.g., glicólisis, ruta de las pentosas fosfato, β-oxidación de lípidos, ciclo de los ácidos tricarboxílicos), la homeostasis de los aminoácidos (en particular aminoácidos de cadena ramificada y aromáticos), las hormonas esteroideas y los fosfolípidos, así como otras alteraciones relacionadas con la microbiota intestinal y factores de exposición ambiental (e.g., dieta). Cabe señalar que este conjunto de complejas perturbaciones bioquímicas y moleculares se vieron por lo general acentuadas entre aquellos sujetos que presentaron resistencia insulínica concomitante a la obesidad infantil, lo que pone de manifiesto la necesidad de implementar herramientas terapéuticas personalizadas en función de la presencia/ausencia de complicaciones metabólicas. Asimismo, encontramos que gran parte de estos trastornos se ven profundamente influenciados por una miríada de factores como el sexo, el estadio puberal y el patrón de secreción de insulina de los sujetos de estudio, lo que subraya la importancia de abordar esta variabilidad interindividual como posible factor de riesgo que contribuye a la susceptibilidad de desarrollar complicaciones asociadas a la obesidad en edad temprana. En conclusión, esta Tesis Doctoral ha permitido demostrar que la obesidad infantil acompañada de síndrome metabólico se caracteriza por profundas alteraciones del metabolismo oxidativo, el cual se ve afectado por una amplia gama de factores individuales (e.g., sexo, estadio puberal, patrón de secreción de insulina) y en el que intervienen diversos mecanismos moleculares estrechamente interrelacionados."],"dc:format":["application/pdf"],"dc:identifier.uri":["http://hdl.handle.net/10498/29467"],"dc:language.iso":["eng"],"dc:rights":["Attribution-NonCommercial-NoDerivatives 4.0 Internacional"],"dc:rights.uri":["http://creativecommons.org/licenses/by-nc-nd/4.0/"],"dc:subject":["childhood obesity","Metabolic Syndrome","oxidative stress","Obesidad infantil","Síndrome metabólico","Estrés oxidativo"],"dc:title":["Study of Erythroid Antioxidant Depletion in Childhood Obesity"],"dc:type":["doctoral thesis"]},"updated_at":"2026-07-24T01:29:47Z"}