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

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 his...

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Autores principales: Sookoian, Silvia, Pirola, Carlos J.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596348/
https://www.ncbi.nlm.nih.gov/pubmed/23516571
http://dx.doi.org/10.1371/journal.pone.0058895
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author Sookoian, Silvia
Pirola, Carlos J.
author_facet Sookoian, Silvia
Pirola, Carlos J.
author_sort Sookoian, Silvia
collection PubMed
description 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.
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spelling pubmed-35963482013-03-20 Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease Sookoian, Silvia Pirola, Carlos J. PLoS One Research Article 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. Public Library of Science 2013-03-13 /pmc/articles/PMC3596348/ /pubmed/23516571 http://dx.doi.org/10.1371/journal.pone.0058895 Text en © 2013 Sookoian and Pirola http://creativecommons.org/licenses/by/4.0/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are properly credited.
spellingShingle Research Article
Sookoian, Silvia
Pirola, Carlos J.
Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease
title Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease
title_full Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease
title_fullStr Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease
title_full_unstemmed Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease
title_short Systems Biology Elucidates Common Pathogenic Mechanisms between Nonalcoholic and Alcoholic-Fatty Liver Disease
title_sort systems biology elucidates common pathogenic mechanisms between nonalcoholic and alcoholic-fatty liver disease
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3596348/
https://www.ncbi.nlm.nih.gov/pubmed/23516571
http://dx.doi.org/10.1371/journal.pone.0058895
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