Iron state in association with retinoid metabolism in non-alcoholic fatty liver disease.
OBJECTIVE
We have recently reported that hyperdynamic state of retinoid metabolism, which may lead to the shortage of retinoid, is observed in patients with non-alcoholic fatty liver disease (NAFLD). Hepatic iron overload, which causes production of reactive oxygen species (ROS), is also frequently seen in NAFLD patients. The aim of the study is to examine iron state and retinoid metabolic state simultaneously, and to clarify the relationship between two disorders.


METHODS
Thirty-six persons, comprising 17 patients with simple steatosis (SS), 11 with NASH, and 8 normal controls (N), were examined on hepatic expression of iron metabolism-related genes including hemojuvelin (HJV), hepcidin (HEPC), transferrin receptor 1 and 2 (TfR1, TfR2), ferroportin (FPN), neogenin (NEO) and ferritin heavy chain (FtH) and hepatic iron contents in addition to expression 51 genes which is involved in retinoid metabolism and antioxidative action.


RESULTS
In patients with NAFLD, expression of HJV, TfR2, FPN, TfR1, FtH, SOD and catalase was increased, compared with that in N. In addition, hepatic iron content, which was increased in NASH, was correlated with expression level of TfR2. Expression of cellular retinoid binding protein (CRBP1), alcohol dehydrogenase 1 (ADH1) and cytochrome P450 26A1(CYP26A1) was significantly correlated with that of HJV, TfR2 and FPN, respectively.


CONCLUSIONS
The results of the present study suggest that the reasons responsible for iron accumulation in NASH in the present study may partly be due to enhanced expression of TfRs, especially TfR2, and hyperdynamic state of retinoid metabolism is closely related to iron metabolism in the disease.
Tsuchiya
Hiroyuki
H
Division of Molecular and Genetic Medicine Division of Regenerative Therapeutics, Department of Genetic Medicine and, Regenerative Therapeutics, Graduate School of Medicine Division of Organ Pathology, Department of Microbiology and Pathology, Tottori University, Japan.
Ashla
An Afida
AA
Hoshikawa
Yoshiko
Y
Matsumi
Yoshiaki
Y
Kanki
Keita
K
Enjoji
Munechika
M
Momosaki
Seiya
S
Nakamuta
Makoto
M
Taketomi
Akinobu
A
Maehara
Yoshihiko
Y
Shomori
Kohei
K
Kurimasa
Akihiro
A
Hisatome
Ichiro
I
Ito
Hisao
H
Shiota
Goshi
G