首页|Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies

Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies

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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 accu-mulation of fat in the liver, and is known to be a cause of cir-rhosis. Although many pathways have been proposed, the cause of NAFLD-linked fibrosis progression is still unclear, which posed challenges for the development of new thera-pies 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.

Non-alcoholic fatty liver diseaseCirrhosisFibrosisGlutaminoly-sisAmmoniaUrea

ángela Rojas、María Rosario García-Lozano、Antonio Gil-Gómez、Manuel Romero-Gómez、Javier Ampuero

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Department of Unit of Digestive Diseases,Virgen del Rocío University Hospital,Seville,Spain

SeLiver group at the Insti-tute of Biomedicine of Seville(IBIS),Virgen del Rocío University Hospital/CSIC/University of Seville,Seville,Spain

Center for the Study of Liver and Gastrointestinal Diseases(CIBERehd),Carlos Ⅲ National Institute of Health,Madrid,Spain

De-partment of Organic and Medicinal Chemistry,Faculty of Pharmacy,University of Seville,E-41071,Seville,Spain

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Spanish Ministry of Economy,Innovation and Competition,Instituto de Salud Car-losⅢSpanish Ministry of Economy,Innovation and Competition,Instituto de Salud Car-losⅢSpanish Ministry of Economy,Innovation and Competition,Instituto de Salud Car-losⅢSpanish Ministry of Economy,Innovation and Competition,Instituto de Salud Car-losⅢSpanish Ministry of Economy,Innovation and Competition,Instituto de Salud Car-losⅢángela Rojas has received the Sara Bor-rell postdoctoral fellowships from Instituto de Salud Carlo

PI19/00589PI19/01404PI16/01842PI17/00535GLD19/00100sⅢCD18/00126

2022

10.14218/JCTH.2021.00247

临床与转化肝病杂志(英文版)

临床与转化肝病杂志(英文版)

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年,卷(期)：2022.10(2)
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