Steatosis, also known as fatty liver, is a pathological process characterized by abnormal accumulation of lipid within cells. There are two distinct patterns of steatosis: macrovesicular and microvesicular. The former is frequently seen in alcohol-induced liver injury, as a complication of metabolic syndrome such as obesity and type II diabetes, and is a marker of the hepatotoxic side effect of certain drugs. Microvesicular steatosis is more commonly related to mitochondrial dysfunction and defects in b-oxidation responsible for fatty liver seen in pregnancy and Reye’s syndrome. While simple steatosis may not be associated with significant impairment of liver function, extensive fat accumulation can lead to cirrhosis and even liver failure. Studies on alcohol-induced steatosis revealed a set of transcription factors which are thought to be involved in the process, including SREBP1, PPARa, and Erg-1. The mechanism of non-alcoholic steatosis formation is poorly understood and little information is available on the pathway(s) responsible for progressive hepatocellular damage following lipid accumulation.

Determining the hepatotoxicity of drug candidates is an essential component of the pharmaceutical discovery process. Steatosis is one of the parameters that is evaluated when determining the hepatoxicity of a drug candidate. In vitro liver models, such as the HepG2 cell line, are available for mechanism-based testing of the hepatotoxic effects of drug candidates. Chloroquine is a well known cationic amphiphilic drug that is known to induce steatosis which is often used as a positive control in drug screening for steatosis.