LAUSR

The prevalence of non-alcoholic fatty liver disease (NAFLD) is now 25% in the general population but increases to more than 55% in subjects with obesity and/or type 2 diabetes. Simple steatosis (NAFL) can develop into more severe, i.e., non-alcoholic steatohepatitis (NASH), cirrhosis, hepatocellular carcinoma and death. In this review we have discussed several mechanisms that have recently been indicated as primary promoters of NAFL progression to NASH. In particular, the role of insulin resistance, mitochondrial function and lipotoxic lipids. Insulin resistance, mainly in adipose tissue, is the main driver of NAFLD due to excess release of fatty acid. We discussed several lipids that are bioactive or toxic to cells and can be used to identify individuals at risk of progression to NASH. Not only lipid, but also amino acid metabolism is impaired in NAFL/NASH, and some amino acids, such as branched-chain and aromatic amino acids, glutamate, serine, and glycine, have been linked to impaired metabolism and severity of NAFLD.