Abstracts Poster Abstracts - Dr Falk

The role of insulin resistance and extra-hepatic signaling infatty liverAnna Mae Diehl, MDDuke University, Durham, North Carolina, USANonalcoholic fatty liver disease (NAFLD) is the hepatic component of the metabolicsyndrome, a systemic state of insulin resistance caused by abnormal production offat- and liver-derived factors that modulate energy substrate flux to coordinate tissueanabolism and catabolism. These factors are produced by multiple types of cells inboth tissues. Many, if not all, of the intermediary metabolism regulators are alsopotent regulators of immune system functions. Conversely, acknowledged immuneregulators, such as cytokines, modulate the production and biological activity of themetabolic factors. Steatosis, steatohepatitis and insulin resistance develop as a resultof excessive proinflammatory factors. Because the metabolic syndrome is a chronicinflammatory state, early stage NAFLD is very common in individuals with thiscondition. However, although chronic exposure to inflammatory mediators generallypromotes the generation of various profibrogenic factors, progression from steatohepatitisto cirrhosis is actually relatively uncommon. This paradox may reflect therequirement for additional factors, such as certain Th-2 cytokines, that are selectivelyinduced in subpopulations of individuals with the metabolic syndrome who haveparticular hepatic innate immune system defects. Defective hepatic innate immunitymay also contribute to the evolution of hepatocellular carcinoma in some patientswith chronic NAFLD. More research is needed to delineate mechanisms that governliver remodeling during conditions of metabolic stress in order to clarify thepathogenesis of NAFLD and prevent its progression.54