Identification of novel biomarkers of altered homeostasis

Identificador:  TDX:2642

Handle: https://hdl.handle.net/20.500.11797/TDX2642

Autores:  Suárez García, Susana

Resumen:
Poor eating habits exert a direct influence on the incidence of chronic diseases of high global prevalence, such as cardiovascular and fatty liver diseases. Nevertheless, the beneficial effects of a correct nutrition are pincipally effective in the opening phase of the metabolic disorder, being able to prevent and even reverse its development. By contrast, current biomarkers have a delayed response, contributing to the late diagnosis of the disease and encouraging the use of pharmacological therapies. These treatments can also be expensive and lead to serious side effects for the patients. Therefore, it is essential to find new risk markers that assist on early diagnosis. Only with these novel biomarkers able to determine the primarily metabolic disturbances that lead into a plethora of diseases, nutrition can be efficient in disease therapy. The recent emergence of the omics sciences along with the improvement of the equipment and tools for the processing of large volumes of data, provide the adequate support for biomarker search. In this context, the present doctoral thesis was aimed to identify novel early biomarkers useful in the diagnosis of metabolic disorders derived for altered nutrition and lifestyle. For this purpose, non-targeted metabolomics was applied to the analysis of plasma samples from rodents fed different diets and subject to behavioral intervention. Once the biomarkers were selected, their distribution and metabolism were further studied. Finally, the adequacy of the putative biomarkers was determined in humans. Our results revealed circulating lysophospholipids as early predictors of chronic disorder. The metabolic assessment of the lysophospholipidome was relevant for the subclinical non-invasive diagnosis of fatty liver. Furthermore, the findings in humans seemed to confirm this assumption. As a conclusion, we propose lysophospholipids, including lysophosphatidylcholines and lysophosphatidylethanolamines, as good candidates for biomarkers of risk of fatty liver in humans.