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Artículo

Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease

Sookoian, Silvia CristinaIcon ; Pirola, Carlos JoseIcon
Fecha de publicación: 07/02/2013
Editorial: Public Library Science
Revista: Plos One
ISSN: 1932-6203
Idioma: Inglés
Tipo de recurso: Artículo publicado
Clasificación temática:
Gastroenterología y Hepatología

Resumen

The abnormal accumulation of fat in the liver is often related either to metabolic risk factors associated with metabolic syndrome in the absence of alcohol consumption (nonalcoholic fatty liver disease, NAFLD) or to chronic alcohol consumption (alcoholic fatty liver disease, AFLD). Clinical and histological studies suggest that NAFLD and AFLD share pathogenic mechanisms. Nevertheless, current data are still inconclusive as to whether the underlying biological process and disease pathways of NAFLD and AFLD are alike. Our primary aim was to integrate omics and physiological data to answer the question of whether NAFLD and AFLD share molecular processes that lead to disease development. We also explored the extent to which insulin resistance (IR) is a distinctive feature of NAFLD. To answer these questions, we used systems biology approaches, such as gene enrichment analysis, protein?protein interaction networks, and gene prioritization, based on multi-level data extracted by computational data mining. We observed that the leading disease pathways associated with NAFLD did not significantly differ from those of AFLD. However, systems biology revealed the importance of each molecular process behind each of the two diseases, and dissected distinctive molecular NAFLD and AFLD-signatures. Comparative co-analysis of NAFLD and AFLD clarified the participation of NAFLD, but not AFLD, in cardiovascular disease, and showed that insulin signaling is impaired in fatty liver regardless of the noxa, but the putative regulatory mechanisms associated with NAFLD seem to encompass a complex network of genes and proteins, plausible of epigenetic modifications. Gene prioritization showed a cancer-related functional map that suggests that the fatty transformation of the liver tissue is regardless of the cause, an emerging mechanism of ubiquitous oncogenic activation. In conclusion, similar underlying disease mechanisms lead to NAFLD and AFLD, but specific ones depict a particular disease signature that has a different impact on the systemic context.
Palabras clave: Liver , Fatty Liver , Systems Biology , Alcohol
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info:eu-repo/semantics/openAccess Excepto donde se diga explícitamente, este item se publica bajo la siguiente descripción: Creative Commons Attribution-NonCommercial-ShareAlike 2.5 Unported (CC BY-NC-SA 2.5)
Identificadores
URI: http://hdl.handle.net/11336/572
URL: http://dx.doi.org/ doi:10.1371/journal.pone.0058895
Colecciones
Articulos(IDIM)
Articulos de INST.DE INVEST.MEDICAS
Citación
Sookoian S; Carlos J Pirola; Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease; Public Library Science; Plos One; 8; 2013-3; 58895-58899;
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