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HERO ID
5932838
Reference Type
Journal Article
Title
Molecular pathways of nonalcoholic fatty liver disease development and progression
Author(s)
Bessone, F; Razori, MV; Roma, MG
Year
2019
Is Peer Reviewed?
Yes
Journal
Cellular and Molecular Life Sciences (CMLS)
ISSN:
1420-682X
EISSN:
1420-9071
Volume
76
Issue
1
Page Numbers
99-128
Language
English
PMID
30343320
DOI
10.1007/s00018-018-2947-0
Abstract
Nonalcoholic fatty liver disease (NAFLD) is a main hepatic manifestation of metabolic syndrome. It represents a wide spectrum of histopathological abnormalities ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) with or without fibrosis and, eventually, cirrhosis and hepatocellular carcinoma. While hepatic simple steatosis seems to be a rather benign manifestation of hepatic triglyceride accumulation, the buildup of highly toxic free fatty acids associated with insulin resistance-induced massive free fatty acid mobilization from adipose tissue and the increased de novo hepatic fatty acid synthesis from glucose acts as the "first hit" for NAFLD development. NAFLD progression seems to involve the occurrence of "parallel, multiple-hit" injuries, such as oxidative stress-induced mitochondrial dysfunction, endoplasmic reticulum stress, endotoxin-induced, TLR4-dependent release of inflammatory cytokines, and iron overload, among many others. These deleterious factors are responsible for the triggering of a number of signaling cascades leading to inflammation, cell death, and fibrosis, the hallmarks of NASH. This review is aimed at integrating the overwhelming progress made in the characterization of the physiopathological mechanisms of NAFLD at a molecular level, to better understand the factor influencing the initiation and progression of the disease.
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