Avances en la regulación de la obesidadmicroARNs, genes y proteínas

Abstract

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.