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Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies
The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, reflecting the current epidemics of obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. NAFLD is characterized by the accumulation of fat in the liver, and is known to be a cause of cirrho...
Autores principales: | , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
XIA & HE Publishing Inc.
2022
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039703/ https://www.ncbi.nlm.nih.gov/pubmed/35528989 http://dx.doi.org/10.14218/JCTH.2021.00247 |
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author | Rojas, Ángela García-Lozano, María Rosario Gil-Gómez, Antonio Romero-Gómez, Manuel Ampuero, Javier |
author_facet | Rojas, Ángela García-Lozano, María Rosario Gil-Gómez, Antonio Romero-Gómez, Manuel Ampuero, Javier |
author_sort | Rojas, Ángela |
collection | PubMed |
description | The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, reflecting the current epidemics of obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. NAFLD is characterized by the accumulation of fat in the liver, and is known to be a cause of cirrhosis. Although many pathways have been proposed, the cause of NAFLD-linked fibrosis progression is still unclear, which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular carcinoma. Cirrhosis is associated with activation of hepatic stellate cells (HSC) and accumulation of excess extracellular matrix proteins, and inhibiting the activation of HSCs would be expected to slow the progression of NAFLD-cirrhosis. Multiple molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC activation. Both mechanisms are plausible antifibrotic targets in NASH, as the activation of HSCs the proliferation of myofibroblasts depend on those processes. This review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression, and shows how the axis could be a novel therapeutic target. |
format | Online Article Text |
id | pubmed-9039703 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2022 |
publisher | XIA & HE Publishing Inc. |
record_format | MEDLINE/PubMed |
spelling | pubmed-90397032022-05-06 Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies Rojas, Ángela García-Lozano, María Rosario Gil-Gómez, Antonio Romero-Gómez, Manuel Ampuero, Javier J Clin Transl Hepatol Review Article The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, reflecting the current epidemics of obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. NAFLD is characterized by the accumulation of fat in the liver, and is known to be a cause of cirrhosis. Although many pathways have been proposed, the cause of NAFLD-linked fibrosis progression is still unclear, which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular carcinoma. Cirrhosis is associated with activation of hepatic stellate cells (HSC) and accumulation of excess extracellular matrix proteins, and inhibiting the activation of HSCs would be expected to slow the progression of NAFLD-cirrhosis. Multiple molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC activation. Both mechanisms are plausible antifibrotic targets in NASH, as the activation of HSCs the proliferation of myofibroblasts depend on those processes. This review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression, and shows how the axis could be a novel therapeutic target. XIA & HE Publishing Inc. 2022-04-28 2022-01-04 /pmc/articles/PMC9039703/ /pubmed/35528989 http://dx.doi.org/10.14218/JCTH.2021.00247 Text en © 2022 Authors. https://creativecommons.org/licenses/by-nc/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-Noncommercial 4.0 International License (CC BY-NC 4.0), permitting all non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Review Article Rojas, Ángela García-Lozano, María Rosario Gil-Gómez, Antonio Romero-Gómez, Manuel Ampuero, Javier Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies |
title | Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies |
title_full | Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies |
title_fullStr | Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies |
title_full_unstemmed | Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies |
title_short | Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies |
title_sort | glutaminolysis-ammonia-urea cycle axis, non-alcoholic fatty liver disease progression and development of novel therapies |
topic | Review Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9039703/ https://www.ncbi.nlm.nih.gov/pubmed/35528989 http://dx.doi.org/10.14218/JCTH.2021.00247 |
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