Recent insights on the role of cholesterol in non-alcoholic fatty liver disease

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dc.catalogadoryvc
dc.contributor.authorArgüello Florencio, Graciela Rosalva
dc.contributor.authorBalboa Castillo, Elisa
dc.contributor.authorArrese Jiménez, Marco Antonio
dc.contributor.authorZanlungo Matsuhiro, Silvana
dc.date.accessioned2024-06-06T19:19:44Z
dc.date.available2024-06-06T19:19:44Z
dc.date.issued2015
dc.description.abstractNon-alcoholic fatty liver disease (NAFLD) encompasses a spectrum of hepatic histopathological changes ranging from non-inflammatory intracellular fat deposition to non-alcoholic steatohepatitis (NASH), which may progress into hepatic fibrosis, cirrhosis, or hepatocellular carcinoma. NAFLD hallmark is the excessive hepatic accumulation of neutral lipids that result from an imbalance between lipid availability and lipid removal. Recent data suggest that disturbed hepatic cholesterol homeostasis and liver free cholesterol (FC) accumulation are relevant to the pathogenesis of NAFLD/NASH. Hepatic FC accumulation in NAFLD results from alterations in intracellular cholesterol transport and from unbalanced cellular cholesterol homeostasis characterized by activation of cholesterol biosynthetic pathways, increased cholesterol de-esterification and attenuation of cholesterol export and bile acid synthesis pathways. FC accumulation leads to liver injury through the activation of intracellular signaling pathways in Kupffer cells (KCs), Stellate cells (HSCs) and hepatocytes. The activation of KCs and HSCs promotes inflammation and fibrogenesis. In addition, FC accumulation in liver mitochondria induces mitochondrial dysfunction, which results in increasing production of reactive oxygen species, and triggers the unfolded protein response in the endoplasmic reticulum (ER) causing ER stress and apoptosis. These events create a vicious circle that contributes to the maintenance of steatosis and promotes ongoing hepatocyte death and liver damage, which in turn may translate into disease progression. In the present review we summarize the current knowledge on dysregulated cholesterol homeostasis in NAFLD and examine the cellular mechanisms of hepatic FC toxicity and its contribution to ongoing liver injury in this disease. The therapeutic implications of this knowledge are also discussed.
dc.fuente.origenORCID
dc.identifier.doi10.1016/j.bbadis.2015.05.015
dc.identifier.urihttps://doi.org/10.1016/j.bbadis.2015.05.015
dc.identifier.urihttps://repositorio.uc.cl/handle/11534/86572
dc.information.autorucDepartamento de Ciencias de la Salud;Argüello Florencio, Graciela Rosalva;S/I;1024133
dc.information.autorucFacultad de Ciencias Biológicas;Balboa Castillo, Elisa;142402
dc.information.autorucEscuela de Medicina;Arrese Jiménez, Marco Antonio;0000-0002-0499-4191;76095
dc.information.autorucEscuela de Medicina; Zanlungo Matsuhiro, Silvana; 0000-0001-8383-9829; 72650
dc.language.isoen
dc.nota.accesocontenido parcial
dc.rightsacceso restringido
dc.subject.ddc610
dc.subject.deweyMedicina y saludes_ES
dc.titleRecent insights on the role of cholesterol in non-alcoholic fatty liver disease
dc.typeartículo
sipa.codpersvinculados72650
sipa.trazabilidadORCID;2024-06-03
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