Iron Perturbations in Human Non-Alcoholic Fatty Liver Disease (NAFLD): Clinical Relevance and Molecular Mechanisms

Non-alcoholic fatty liver disease (nafld) is the hepatic manifestation of the insulin resistance syndrome and thus afrequent cause of elevated liver enzymes. the term insulin-resistance associated hepatic iron overload syndrome (irhios)has been coined to describe the frequent association of hepatic steatosis with increased levels of serum ferritin,normal or slightly elevated transferrin saturation and mild hepatic iron deposition. there is mounting evidence thatincreased iron stores in insulin resistance are associated with an unfavorable course of the disease and an increasedprevalence of associated conditions such as diabetes, hypertension or cardiovascular disease. iron depletion viaphlebotomy has been demonstrated to improve several aspects of the insulin-resistance syndrome. multipleinteractions have been observed between molecules of iron and glucose metabolism. on a molecular level, impaired ironexport has been demonstrated to be the principal mechanism of iron accumulation in fatty liver disease. obesity-relatedinflammation, low ferroxidase activity associated with low copper bioavailability and decreased expression of the ironexport molecule ferroportein have so far been identified as contributors to increased iron accumulation in humannafld.