Underlying metabolic processes behind non-alcoholic fatty liver disease in population with metabolic syndrome features: Nutritional status and non-invasive liver tools

espanolLa enfermedad del higado graso no alcoholico (EHGNA) es actualmente la causa mas comun de enfermedad hepatica en el mundo occidental, afectando a un 20-30% de la poblacion adulta en general. Es un problema creciente debido al aumento de la prevalencia de patologias que contribuyen a su desarrollo como la obesidad y el estado inflamatorio. El metodo de diagnostico de referencia para EHGNA es la biopsia hepatica, dificultando el seguimiento a grandes grupos de poblacion durante un largo periodo de tiempo. Por ello, es necesario identificar herramientas de dano hepatico no invasivas que faciliten su diagnostico y su pronostico. La principal base terapeutica es la modificacion del estilo de vida a traves de la dieta y el ejercicio. Este trabajo de investigacion tuvo como objetivos: 1) evaluar la posible asociacion entre un indice inflamatorio de la dieta (DII) con marcadores no invasivos del estado hepatico en sujetos con sobrepeso/obesidad y riesgo cardiovascular; 2) evaluar la influencia de dos dietas con restriccion energetica sobre marcadores no invasivos de dano hepatico en individuos con sobrepeso/obesidad y con criterios de sindrome metabolico tras seis meses de seguimiento nutricional, asi como evaluar el papel de la fibra en las variables clinicas estudiadas; 3) evaluar la influencia de la perdida de peso sobre el metabolismo de los lisofosfolipidos (LP) y el estado hepatico en sujetos con sobrepeso/obesidad, asi como proporcionar evidencia sobre la interaccion del metabolismo de LP como un factor clave en el manejo de higado graso no alcoholico y obesidad; 4) evaluar cambios en el FGF-21 tras seguimiento de una intervencion de perdida de peso y su posible interaccion con otros biomarcadores inflamatorios de dano hepatico; 5) evaluar el estado hepatico mediante tecnologia validada y comparar los resultados obtenidos mediante tecnicas de imagen, marcadores sanguineos de rutina y un test lipidomico con el resultado de la resonancia magnetica (RM) en sujetos con EHGNA. En relacion con el primer objetivo, los resultados muestran que el consumo de un patron dietetico antiinflamatorio podria contribuir a la reduccion de la obesidad y las comorbilidades relacionadas, especialmente al abordaje de EHGNA mediante el diseno de patrones dieteticos personalizados y de precision. En cuanto al segundo objetivo, se concluye que el diseno de patrones dieteticos con restriccion energetica y basados en el consumo de fibra insoluble y fibra proveniente de las frutas son una buena opcion para el manejo de pacientes obesos con EHGNA. El tercer estudio evidencia una reduccion en los niveles circulantes de LP despues de una intervencion dietetica con restriccion energetica, asi como su relacion con marcadores del estado hepatico (FLI, BAAT score) y la circunferencia de la cintura. El cuarto articulo muestra una reduccion en los niveles de FGF-21 despues del seguimiento de una restriccion energetica, asi como la interaccion con biomarcadores inflamatorios hepaticos, especificamente M30 y PAI-I. Finalmente, en relacion con el quinto objetivo, los resultados muestran que la ecografia, un test metabolomico y un panel que incluye marcadores sanguineos de rutina vinculados a resistencia insulinica, mostraron elevados valores de prediccion utilizando como referencia metodologica la resonancia magnetica, sugiriendo que estas herramientas podrian contribuir en el diagnostico y pronostico de EHGNA. EnglishNon-alcoholic fatty liver disease (NAFLD) is currently the most common cause of liver disease in the Western world, affecting up to 20-30% of the general adult population. It is a growing public health problem, because of the increasing prevalence of the pathologies that contribute to its development such as obesity and inflammation status. The diagnostic method of choice for NAFLD is liver biopsy, but since it is a long-standing disease, it is difficult to follow large population groups through serial biopsies. Therefore, it is necessary to identify noninvasive liver damage tools that facilitate the diagnosis and prognosis of the disease and allow for the establishment of a follow-up protocol that prevents progression to severe stages of NAFLD. Moreover, the main therapeutic basis is the modification of lifestyle through diet and exercise In this context, this research work aimed: 1) to assess the possible association between a validated Dietary Inflammatory Index (DII) and specific dietary components with suitable non-invasive markers of liver status in overweight/obese subjects with cardiovascular risk; 2) to evaluate the influence of two energy-restricted diets on non-invasive markers and scores of liver damage in overweight/obese individuals with features of metabolic syndrome after six months of follow-up and to assess the role of fiber content in metabolic outcomes; 3) to assess the influence of weight loss on lysophospholipid metabolism and liver status in overweight/obese subjects as well as to provide new evidence regarding the interaction of lysophospholipids metabolism as a key factor in the onset and management of obesity-related diseases such as liver damage; 4) to analyze the response of FGF-21 after a weight loss intervention and the relationships with other putative inflammatory liver biomarkers; 5) to evaluate the fatty liver status by several validated approaches and to compare imaging techniques, lipidomic and routine blood markers with magnetic resonance imaging (MRI) in adults subjects with NAFLD. In relation with the first objective, the results of this chapter evidended that the consumption of an anti-inflammatory dietary pattern might contribute to the reduction of obesity and related comorbidities, especially NAFLD through precision nutrition guidelines. Concerning the second objective, we concluded that the design of dietary patterns based on the consumption of insoluble fiber and fiber from fruits in the context of energy restriction is a good choice the management of obese patients suffering from NAFLD. The third chapter suggested a generalized decrease in circulating lysophospholipids (LP), particularly lysophosphatidylcholine, after a weight loss intervention in a population with metabolic syndrome features. Changes in fatty liver index, waist circumference and BAAT score revealed positive association with lysophosphatidylcholine score. The involvement of particular LP in liver metabolism and obesity merits further attention. The fourth chapter revealed that FGF-21 changes exhibit a great association with non-alcoholic fatty liver inflammation, M30 fragment and PAI-I, independently of weight loss. These findings suggest that FGF-21 is involved in the obesity-inflammation-liver process. Finally, in relation to the fifth objective we concluded that ultrasonography, a metabolomic test and a panel combination including routine blood markers linked to insulin resistance showed the highest associations with MRI, which is considered the gold standard for non-invasive liver fat content assessment, suggesting these tools could contribute to the diagnosis and prognosis of NAFLD.