Dysregulation of systemic iron metabolism in alcoholic liver diseases.
Alcoholic liver diseases (ALD) are frequently associated with iron overload. Until recently, the effects of ethanol in hepatic iron uptake and intestinal iron absorption have not been clarified in detail. Two possible mechanisms for iron overload are the uptake of iron into hepatocytes in a specific manner through the increased expression of transferrin receptor (TfR) 1; and increased intestinal iron absorption by the lowering of hepcidin. It is worthwhile to examine whether a similar mechanism is present in the development of steatosis and non-alcoholic steatohepatitis (NASH). Hepatocytes have several iron uptake pathways. Ethanol increases transferrin (Tf)-mediated uptake via a receptor-dependent manner, but downregulates the non-Tf-bound iron uptake. According to immunohistochemical study, TfR1 was increased in hepatocytes in 80% of hepatic tissues of patients with ALD, but was not detected in normal hepatic tissues. In an experimental model, ethanol exposure to the primary cultured-hepatocytes in the presence of iron increased TfR1 expression and (59)Fe-labeled Tf uptake. In patients with ALD, intestinal iron absorption is increased by oral iron uptake assay. The regulatory hormone for iron homeostasis, hepcidin is downregulated in ethanol-loaded mice liver. As well as ALD, a similar mechanism was present in the mouse model fed with a high-fat diet, a model of the initial phenomenon of steatosis. The common mechanism for hepatic iron deposition and the triggering role of iron may be present in the development of ALD and non-alcoholic fatty liver disease/NASH.
Kohgo
Yutaka
Y
Division of Gastroenterology and Hematology/Oncology, Department of Medicine, Asahikawa Medical College, Asahikawa, Japan. yk1950@asahikawa-med.ac.jp
Ohtake
Takaaki
T
Ikuta
Katsuya
K
Suzuki
Yasuaki
Y
Torimoto
Yoshihiro
Y
Kato
Junji
J
D000818:Animals; D019189:Iron Metabolism Disorders / Q000209:etiology*; D008108:Liver Diseases, Alcoholic / Q000150:complications* / Q000378:metabolism; D051379:Mice