Abstract
BackgroundNon-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Both iron and lipid metabolism seem to be involved in its pathogenesis. We aimed to assess the relationship between levels of hepcidin, the master iron-regulatory protein, in plasma and the presence of NAFLD in morbidly obese (MO) patients, and to investigate the association between the hepatic expression of the main iron and lipid metabolism -related genes.Materials and methodsEnzyme-linked immunosorbent assay was used to measure plasma hepcidin levels in 49 normal-weight control women, 23 MO women with normal liver (NL) histology and 46 MO women with NAFLD. The mRNA expression of hepcidin, the main iron metabolism-related genes, and the main lipid-metabolism genes was quantified by qRT-PCR in liver biopsies from members of the MO group undergoing bariatric surgery.ResultsCirculating hepcidin levels were significantly greater in MO than in normal-weight control women. However, there were no significant differences between MO women with NL and those with NAFLD. PCR analysis showed increased expression of hepcidin, FPN1, TfR1 and TfR2 in the liver of MO NAFLD women compared to those with NL. Moreover, a positive association of hepatic hepcidin mRNA expression and the iron metabolism-related genes was found with some key genes involved in the lipid metabolism.ConclusionThese findings suggest that circulating hepcidin levels are associated with obesity but not with the presence of NAFLD. However, the hepatic expression of hepcidin and the iron metabolism-related genes seem to play a role in regulating lipid metabolism pathways in liver, which has implications for NAFLD pathogenesis.
Highlights
Non-alcoholic fatty liver disease (NAFLD) is a wide spectrum liver disease, ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH)
A positive association of hepatic hepcidin mRNA expression and the iron metabolism-related genes was found with some key genes involved in the lipid metabolism
These findings suggest that circulating hepcidin levels are associated with obesity but not with the presence of NAFLD
Summary
Non-alcoholic fatty liver disease (NAFLD) is a wide spectrum liver disease, ranging from simple steatosis (SS) to non-alcoholic steatohepatitis (NASH). Lipid accumulation alone may be benign, more aggressive forms of NAFLD can develop as a result of other mechanisms In this regard, the most generally accepted hypothesis at present to explain the progression from SS to NASH is the “multiple hit” hypothesis, which considers multiple insults acting together, including hormones secreted from the adipose tissue, oxidative stress, mitochondrial dysfunction, gut microbiota, genetic and epigenetic factors, and iron overload [5,6,7,8]. Non-alcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver disease in Western countries. Both iron and lipid metabolism seem to be involved in its pathogenesis. We aimed to assess the relationship between levels of hepcidin, the master ironregulatory protein, in plasma and the presence of NAFLD in morbidly obese (MO) patients, and to investigate the association between the hepatic expression of the main iron and lipid metabolism -related genes.
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