Lipidomic biomarkers and mechanisms of lipotoxicity in non-alcoholic fatty liver disease

• Published in: Free radical biology & medicine 2019-11, Vol.144, p.293-309
• Main Authors: Svegliati-Baroni, Gianluca, Pierantonelli, Irene, Torquato, Pierangelo, Marinelli, Rita, Ferreri, Carla, Chatgilialoglu, Chryssostomos, Bartolini, Desirée, Galli, Francesco
• Format: Article
• Language: English
• Subjects: Arachidonic acid; DHA; Eicosanoids; Erythrocyte membrane fatty acids; Lipid peroxidation; Lipidomics; Lipotoxicity; Non-alcoholic fatty liver disease; Non-alcoholic steatohepatitis; Oxidant stress; Polyunsaturated fatty acids; Vitamin E
• ISSN: 0891-5849; 1873-4596
• DOI: 10.1016/j.freeradbiomed.2019.05.029

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 fibrosis, which increase the risk of developing liver failure, cirrhosis and hepatocellular carcinoma. 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 the liver cells is not the main determinant of lipotoxicity and that specific lipid classes act as damaging agents. These lipotoxic species affect the cell behavior via multiple mechanisms, including activation of death receptors, endoplasmic reticulum stress, modification of mitochondrial function and oxidative stress. The gut microbiota, which provides signals through the intestine to the liver, is also reported to play a key role in lipotoxicity. Finally, we summarize the most recent lipidomic strategies utilized to explore the liver lipidome and its modifications in the course of NALFD. These include measures of lipid profiles in blood plasma and erythrocyte membranes that can surrogate to some extent lipid investigation in the liver. [Display omitted] •Non-alcoholic fatty liver disease (NAFLD) is a highly prevalent form of chronic liver disease worldwide.•3–5% of NAFLD patients develop non-alcoholic steatohepatitis (NASH) and have higher risk of hepatocellular carcinoma.•Lipid accumulation generates toxic effects leading to hepatocellular damage and inflammation i.e. lipotoxicity.•Lipotoxic species and their cellular and molecular effects/mechanisms are reviewed.•The role of gut microbiota and gut-liver axis in lipotoxicity is also described.•Lipidomic strategies utilized to explore the liver lipidome and its modifications in NALFD are summarized.