[en] Overweight and obesity are defined by the World Health Organization as an abnormal or excessive fat that accumulate and present a risk to health. Since the 1980s, the prevalence of obesity has doubled and almost tripled in more than 70 countries, mainly in developed and developing countries, and continues to increase year after year. The comorbidities associated with this pathology make it an important risk to health by increasing the mortality rate of people who suffer it. Given the etiogenic nature of this disease, in this thesis we decided to investigate the molecular basis of this disease from several approaches: 1.- We studied several epigenetic mechanism, specifically different microRNAs that could be involved in the differentiation of the adipocytes and in the regulation of obesity. For that, we used an in vitro model (the cell line of preadipocytes 3T3-L1) in order to determine the role of MIR-19 and MIR-200 families in adipogénesis, we used animal models (rats reared with different diets) and finally, we used human subcutaneous adipose tissue samples from volunteers with normal BMI and with obesity. 2.- Study of the proteomic profile of the subcutaneous adipose tissue of obese patients and the same candidates after the weight loss induced by bariatric surgery using mass spectrometry and confirmation of several obtained results by western blot and real-time polymerase chain reaction. 3.- And the study of the circulating levels of irisin (hormone recently related to exercise and browning) and the expression levels of its precursor, FNDC5, under different stages of metabolic stress. With this studies, we were able to demonstrate: - The implication of miR-19a, miR-19b and miR-200c in the adipogenesis process, as well as the deregulation of miR-19b and miR-200c during morbid obesity in humans, while in animal models we observed a greater effect of the diet on the visceral adipose tissue microRNAs expression compared to the other studied tissues. - The existence of differences in the proteomic profile of the subcutaneous adipose tissue of morbid obese patients and the same patients after weight loss, with improvement in metabolic and inflammatory processes after weight loss. - Differences in the central and peripheral control of FNDC5 gene expression and circulating irisin levels under different metabolic stages.

[gl] A obesidade e o sobrepeso están definidos pola Organización Mundial da Saúde como unha acumulación anormal ou excesiva de graxa corporal. Dende os anos 80 a prevaleza da obesidade duplicouse e case triplicouse en máis de 70 países, principalmente en países desenvolvidos e en vías de desenvolvemento, e continúa medrando ano tras ano. As comorbilidades asociadas a esta patoloxía fan que sexa un risco importante para a saúde aumentando a taxa de mortalidade das persoas que a padecen. Dada a natureza etioxénica desta enfermidade, nesta tese de doutoramento decidimos investigar sobre as bases moleculares desta doenza dende varias aproximacións: 1.- Estudamos diversos mecanismos epixenéticos, concretamente diversos microARNs que puidesen estar implicados na diferenciación dos adipocitos e na regulación da obesidade. Para iso empregamos un modelo in vitro (a liña celular de preadipocitos 3T3-L1) co fin de determinar o papel das familias MIR-19 e MIR-200 na adipoxénese, usamos modelos animais (ratas tratadas con distintas dietas) e por último usamos mostras de tecido adiposo subcutáneo humano de voluntarios con IMC normal e con obesidade. 2.- Estudo do perfil proteómico do tecido adiposo subcutáneo de doentes obesos e os mesmos candidatos tras a perda de peso inducida pola cirurxía bariátrica empregando espectrometría de masas e confirmación de varios dos resultados obtidos mediante Western blot e reacción en cadea da polimerasa en tempo real. 3.- E estudo dos niveis circulantes de irisina (hormona relacionada recentemente co exercicio e o browning) e os niveis de expresión xénica do seu precursor, FNDC5, baixo diferentes estadios de estrés metabólico. Con estes estudos, fomos capaces de demostrar: - A implicación de miR-19a, miR-19b e miR-200c no proceso da adipoxénese, así como a desregulación de miR-19b e miR-200c durante a obesidade mórbida en humanos, mentres que en modelos animais observamos un maior efecto da dieta na alteración da expresión dos microARNs do tecido adiposo visceral fronte ó resto de tecidos estudados. - A existencia de diferenzas no perfil proteómico do tecido adiposo subcutáneo de doentes obesos mórbidos e os mesmos tras a perda de peso observándose melloría tras a perda de peso en procesos metabólicos, inflamatorios, etc. - Diferenzas no control central e periférico da expresión xénica de FNDC5 e irisina circulante baixo distintos estadios metabólicos.