Cadmium exposure exacerbates hyperlipidemia in cholesterol-overloaded hepatocytes via autophagy dysregulation.

Cadmium exposure exacerbates hyperlipidemia in cholesterol-overloaded hepatocytes via autophagy dysregulation.

Toxicology. 2018 Feb 24;:

Authors: Rosales-Cruz P, Domínguez-Pérez M, Reyes-Zárate E, Bello-Monroy O, Enríquez-Cortina C, Miranda-Labra R, Bucio L, Gómez-Quiroz LE, Rojas-Del Castillo E, Gutiérrez-Ruíz MC, Souza-Arroyo V

Abstract
Metabolic factors are the major risk of non-alcoholic fatty liver disease, although other factors may contribute steatosis. Cadmium exposure produces histopathological and molecular changes in liver, which are consistent with steatosis. In the present study, we describe the effect of low cadmium acute treatment on hepatocytes obtained from mice fed with a high cholesterol diet. Our data suggest that hepatocytes with cholesterol overload promote an adaptive response against cadmium-induced acute toxicity by up-regulating anti-apoptotic proteins, managing ROS overproduction, increasing GSH synthesis and MT-II content to avoid protein oxidation. Cadmium treatment increases lipid content in cholesterol-fed mice hepatocytes because of an impaired autophagy process. Our data suggest an essential function of macroautophagy in the regulation of lipid storage induced by Cd on hepatocytes, that implies that alterations in this pathway may be a mechanism that aggravates hepatic steatosis.

PMID: 29486218 [PubMed - as supplied by publisher]

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