Identification of Lipid Species Linked to the Progression of Non-alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) is histologically characterized by the aberrant accumulation of lipid droplets in the liver, which is positively correlated with insulin resistance. Within the spectrum of this disease, patients can develop hepatitis and cirrhosis; i.e., non-alcoholic steatohepatitis (NASH). The mechanisms responsible for the progression of NAFLD are not fully understood. Triacylglycerol (TAG), which is mainly found in lipid droplets, is currently considered to act as a buffer against the accumulation of non-TAG toxic lipid species. In line with this, recent studies have revealed that insulin resistance is driven by the accumulation of phosphatidic acid and diacylglycerol in hepatocytes and that cholesterol-overloaded stellate cells are associated with fibrosis in the liver. Therefore, it is important to identify the toxic lipid species that contribute to NAFLD progression in order to clarify the pathogenesis of NASH and find novel targets for its treatment. In this review, we divided lipids into five classes; i.e., into fatty acyls, glycerophospholipids, glycerolipids, sphingolipids, and sterol lipids, and described their molecular structures, distributions, and metabolism under physiological conditions, as well as the contributions they make to the progression of NAFLD.