Mastoridou, E.M.; Goussia, A.C.; Kanavaros, P.; Charchanti, A.V. Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets. Int. J. Mol. Sci.2023, 24, 15891.
Mastoridou, E.M.; Goussia, A.C.; Kanavaros, P.; Charchanti, A.V. Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets. Int. J. Mol. Sci. 2023, 24, 15891.
Mastoridou, E.M.; Goussia, A.C.; Kanavaros, P.; Charchanti, A.V. Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets. Int. J. Mol. Sci.2023, 24, 15891.
Mastoridou, E.M.; Goussia, A.C.; Kanavaros, P.; Charchanti, A.V. Involvement of Lipophagy and Chaperone-Mediated Autophagy in the Pathogenesis of Non-Alcoholic Fatty Liver Disease by Regulation of Lipid Droplets. Int. J. Mol. Sci. 2023, 24, 15891.
Abstract
Non-alcoholic fatty liver disease (NAFLD) is defined as the accumulation of lipids in the form of lipid droplets in more than 5% of hepatocytes. It is regarded as a range of diverse pathologies, including simple steatosis and steatohepatitis. The structural characteristics of lipid droplets have been implicated in the etiology of the disease, along with their protein composition, mainly perilipins. These proteins have garnered increasing attention as a pivotal regulator, since their levels and distinct expression appear to be associated with the progression from simple steatosis to steatohepatitis. Perilipins are target proteins of chaperone-mediated autophagy, and their degradation is a prerequisite for lipolysis and lipophagy to access the lipid core. Both lipophagy and chaperone-mediated autophagy have significant implications in the development of the disease, as evidenced by their upregulation during the initial phases of simple steatosis, and their subsequent downregulation once steatosis is established. On the contrary, during steatohepatitis, the process of chaperone-mediated autophagy is enhanced, although lipophagy remains suppressed. Evidently, the reduced levels of autophagic pathways observed in simple steatosis serve as a defensive mechanism against lipotoxicity. Conversely, in steatohepatitis chaperone mediated autophagy fails to compensate for the continuous generation of small lipid droplets and thus cannot protect hepatocytes from lipotoxicity.
Medicine and Pharmacology, Gastroenterology and Hepatology
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