Lipid metabolism in hepatic steatosis

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are conditions in which an excess of lipid, principally triglycerides (TGs), accumulates in hepatocytes. In early NAFLD, simple hepatocellular steatosis is the only histologic abnormality, while NASH, by definition, exhibits some degree of inflammation or fibrosis, often in association with other histologic features such as Mallory bodies [1,2]. It is thought that simple steatosis generally precedes NASH, and that the disordered lipid metabolism that leads to steatosis is the first hit in a multi-stage progression to NASH [3–8]. NASH, in turn, may progress to cirrhosis and end-stage liver disease. Development of NASH, however, is by no means a foregone conclusion in all cases of NAFLD, which is, in fact, reversible in many instances. If the alterations of hepatic lipid metabolism leading to NAFLD were understood, it might be possible to prevent or reverse steatosis before progression to steatohepatitis. This goal becomes especially critical, because NAFLD, like obesity, is often a disease of affluence, and its prevalence is increasing along with obesity. The widespread and increasing prevalence of obesity in the United States [9,10] is documented by sequential surveys conducted by the National Center for Health Statistics, Centers for Disease Control and Prevention (CDC). These include the National Health Examination Survey (NHES I, 1960 to 1962) and the National Health and Nutrition Examination Surveys (NHANES) I (1971 to 1974), II (1976 to 1980), and III (1988 to 1994). In 1999, the NHANES surveys