G. Svegliati-Baroni, I. Pierantonelli, P. Torquato, R. Marinelli, C. Ferreri, C. Chatgilialoglu, D. Bartolini, F. Galli
Free radical biology & medicine, 2019
Non-alcoholic fatty liver disease (NAFLD) represents the most common form of chronic liver disease worldwide (about 25% of the general population); and 3-5% of patients develop non-alcoholic steatohepatitis (NASH), characterized by hepatocytes damage, inflammation and/or fibrosis, which can progress to cirrhosis and/or develop hepatocellular carcinoma (HCC). The pathogenesis of NAFLD, particularly the mechanisms whereby a minority of patients develop a more severe phenotype is still incompletely understood. In this review we examine the available literature on initial mechanisms of hepatocellular damage and inflammation, deriving from toxic effects of excess lipids. Accumulating data indicate that the total amount of triglycerides stored in hepatocytes is not the major determinant of lipotoxicity and that specific lipid classes act as damaging agents on liver cells. These lipotoxic agents affect the cell behavior via multiple mechanisms, including activation of death receptors, endoplasmic reticulum stress, modification of mitochondrial function and oxidative stress. The role of gut microbiota, which provides signals through the intestine, in lipotoxicity is also described. Finally, we summarize the lipidomic strategies utilized to explore the liver lipidome and its modifications in the course of NALFD. These include surrogate measures on blood plasma and erythrocyte membrane lipids.
Cited by 44 publications.
Field of study: Medicine