The spectrum of nonalcoholic fatty liver disease (NAFLD) includes a nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The specific types and amounts of lipids that accumulate in NAFLD are not fully defined. The free fatty acid (FFA), diacylglycerol (DAG), triacylglycerol (TAG), free cholesterol (FC), cholesterol ester, and phospholipid contents in normal livers were quantified and compared to those of NAFL and NASH, and the distribution of fatty acids within these classes was compared across these groups. Hepatic lipids were quantified by capillary gas chromatography. N onalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in North America. 1 NAFLD is associated with insulin resistance and the metabolic syndrome. 2,3 The clinical-histologic spectrum of NAFLD extends from a nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). 4 Although NASH is distinguished from NAFL by the presence of cytologic ballooning and inflammation, both conditions are characterized by a fatty liver. 4,5 Thus, hepatic fat accumulation is the hallmark of NAFLD.The compositions of the lipids that accumulate in the livers of subjects with NAFLD are not well characterized. Most of the published literature has focused on triglyceride accumulation as the key defect in NAFLD. 6,7 However, it is not known whether there are substantial changes in other lipid classes, such as cholesterol and specific phospholipids (PLs). Although an increase in the n-6:n-3 fatty acid ratio in total lipids in NAFLD has been described recently, 8,9 the distribution of these fatty acids within specific lipid classes has not been extensively characterized. Given the important biological activities of many lipids, such information could provide potential insights into the pathophysiology of NAFLD and the metabolic syndrome.A lipidomic approach was taken to quantify the major lipid classes and the distribution of fatty acids within these classes in the liver. The specific aims of the study were to (1) quantify the absolute and relative amounts of free fatty acids (FFAs), diacylglycerol (DAG), triacylglycerol

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The global emergence of obesity as an epidemic has made fatty liver disease a public health problem in the Western world. The increased incidence of obesity has been paralleled by an increase in metabolic syndrome in the same cohort of patients. The net consequence of insulin resistance in a large majority of these obese individuals is hepatic steatosis, which over time in a proportion of these patients progresses to steatohepatitis and cirrhosis. Despite the increased awareness among physicians regarding its presence, the diagnostic process has been hampered by the lack of sensitive and specific population-based screening tests. Liver biopsy remains the gold standard for diagnosis as well as for grading and staging of the disease process but its precise role in the diagnostic conundrum continues to be debated.

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Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease observed in the clinical practice of hepatology. The coexistence of metabolic syndrome in this cohort of patients has made insulin resistance central to the pathogenesis of these disorders. The metabolic consequence of insulin resistance is impaired hepatic glucose output and abnormal lipid handling. In the face of continued metabolic insults the normal hepatic regulatory mechanism gets overwhelmed and fat accumulates in the hepatocytes. The subsequent fate of steatotic hepatocytes depends on the capacity of additional factors such as adipocytokines and toxicity induced by the free fatty acids themselves to induce inflammatory response. This latter process is responsible for the producing the phenotype of non-alcoholic steatohepatitis (NASH). Irrespective of the process by which these phenotypic response occurs, it is now universally accepted that in the absence of insulin resistance the spectrum of changes one associates with NAFLD does not develop. In this review we will discuss the various processes that are involved in the pathogenesis of NAFLD.