Insulin resistance in NASH

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.