Interactions between hepatic iron and lipid metabolism with possible relevance to steatohepatitis

Abstract

The liver is an important site for iron and lipid metabolism and the main site for the interactions between these two metabolic pathways. Although conflicting results have been obtained, most studies support the hypothesis that iron plays a role in hepatic lipogenesis. Iron is an integral part of some enzymes and transporters involved in lipid metabolism and, as such, may exert a direct effect on hepatic lipid load, intrahepatic metabolic pathways and hepatic lipid secretion. On the other hand, iron in its ferrous form may indirectly affect lipid metabolism through its ability to induce oxidative stress and inflammation, a hypothesis which is currently the focus of much research in the field of non-alcoholic fatty liver disease/non-alcoholic steatohepatitis (NAFLD/NASH). The present review will first discuss how iron might directly interact with the metabolism of hepatic lipids and then consider a new perspective on the way in which iron may have a role in the two hit hypothesis for the progression of NAFLD via ferroportin and the iron regulatory molecule hepcidin. The review concludes that iron has important interactions with lipid metabolism in the liver that can impact on the development of NAFLD/NASH. More defined studies are required to improve our understanding of these effects.

Iron Overload Reduces Cholestrol and Triglyceride Serum of Mice

“…Thus, iron accumulation in the liver may interact and alter hepatic lipid metabolism. [9,15] Previous study about alteration of cholesterol synthesis in iron overload condition showed that from various genes related to cholesterol synthesis, some genes showed unsignificant increase of expression while a gene showed negative correlation with increase of cholesterol synthesis. [14] The other study also revealed decline of both forms of 3-hydroxy 3-methylglutaryl Iron overload has corelation with lipid metabolism, however the conclusion is still debatable.…”

“…Meanwhile, other study about hepatic iron overload using carbonyl iron in the methionine-choline deficient rat model of NAFLD is associated with decreased hepatic triglyceride. [9] Another study of iron overload in humans homozygous for the Cys282-Tyr (C282Y) mutation in HFE, which causes hemochromatosis, plasma low-density lipoprotein (LDL) cholesterol has been found to be reduced. Besides, there was also negative correlation between iron overloas and upregulation of transcriptions of Abca1 and Abcb4 which related to cholesterol export to the plasma.…”

“…Besides, hepatic iron level enhancement may cause upregulation of the transcription of seven enzymes related to cholesterol synthesis, in other words, it increases hepatic cholesterol synthesis. [9] Iron overload also increases intracellular lipid droplets formation through higher expression of 1D cluster (Class 1 inconventional MHC) which related to pathogenesis of non-alcoholic steatohepatitis. [9,14] The underlying mechanism of relationship between metabolism alteration due to iron overload condition in the liver is remain uncertain.…”

“…[9] Iron overload also increases intracellular lipid droplets formation through higher expression of 1D cluster (Class 1 inconventional MHC) which related to pathogenesis of non-alcoholic steatohepatitis. [9,14] The underlying mechanism of relationship between metabolism alteration due to iron overload condition in the liver is remain uncertain. This study is aimed to investigate the effect of iron overload to triglyceride and cholesterol level in the serum of mice.…”

“…[6][7][8] In the iron overload condition, liver would have higher iron deposit leads to hepatic iron overload condition and end up with liver fibrosis. [6,[8][9][10] Hepatic iron overload would likely to generate free radicals and lipid peroxidation causing progressive hepatic injury result in fibrosis, cirrhosis and hepatocyte carcinoma. [11][12][13] Hepatic iron overload is suggested having relation with alteration of hepatic lipid metabolism.…”