Estudio de las células sanguíneas como fuente de marcadores transcriptómicos de utilidad para la investigación de la obesidad y sus complicaciones

Abstract

Introduction: Diet is a major determinant of our health/disease status, and it is one of main factors contributing to the development of obesity. Then, it would be interesting to dispose of easily obtainable biomarkers to determine how the diet affects our metabolism. Particularly, early biomarkers of obesity are of special interest, since they would allow implementing prevention strategies before the appearance of the disease. This thesis is focused in the analysis of the utility of a blood cell fraction, the peripheral blood mononuclear cells (PBMC), as a source of obesity biomarkers, used for the prevention or treatment of obesity using rodents as animal model. Research content: First, we have studied the ability of PBMC to reflect energy homeostatic impairment during the development of diet-induced obesity, testing their response to changes in feeding conditions (fasting and re-feeding), as well as testing PBMC capacity to reflect metabolic recovery associated to weight lost in after switching an obesogenic to a control balanced diet. Our results show that PBMC are good indicators of metabolic adaptations to fasting and re-feeding, as well as of fasting insensibility observed in cafeteria-obese animals since early stages of obesity development. Moreover, these cells are able to reflect the metabolic recovery associated to weight loss, as recovery of fasting response of serum parameters and of gene expression. PBMC of animals fed hyperlipidic diets also reflect alteration in basal expression of genes involved in different pathways related to body weight control and in inflammatory processes, providing a characteristic obesogenic gene expression profile. On the other hand, we have analysed the ability of PBMC to reflect brown adipose tissue activation or white adipose tissue browning (new focus of interest in obesity treatment) in response to the intake of obesogenic diets or as a result of cold exposure. The results of this second aim show how the intake of obesogenic diets, as well as cold exposure, can induce the expression of brown/brite adipocyte markers in PBMC, reflecting the browning process that occurs in white adipose tissue. Thus, these blood cells constitute a suitable biological material for the analysis of nutritional or pharmacological compounds that could induce white to brown adipose tissue remodelling or activate brown adipose tissue, increasing in this way energy dissipating capacity, opening new perspectives for obesity treatment. Conclusion: PBMC are a good tool for energy homeostatic studies, and constitute an easily obtainable source of early obesity biomarkers useful to study the development of strategies for the prevention and treatment of obesity and related diseases. Moreover, PBMC reflect the white adipose tissue browning process induced by different stimuli, such as the intake of fat-rich diets or cold exposure. According to these results we can state that PBMC offer new therapeutic possibilities and provide an interesting material to identify early markers of disease, which can be useful in human studies.