Expression profile of lipid metabolism-associated genes in hepatitis C virus-infected human liver.
OBJECTIVE
Recent studies have shown that lipid metabolic pathways are required for the entry, replication and secretion of hepatitis C virus (HCV). Although little is known about the life cycle of HCV in humans, the activation of cholesterol and fatty acid biosynthesis may be critical for HCV proliferation.


METHODS
We assessed the transcription levels of genes essential for cholesterol and fatty acid biosynthesis in liver samples obtained from patients with chronic hepatitis C and determined their correlations. The serum levels of low-density lipoprotein (LDL) cholesterol and HCV core antigen were also measured.


RESULTS
The gene expression of the LDL receptor (LDLR) was suppressed, whereas that of SREBP1c, liver X receptor-α (LXRα), fatty acid synthase (FASN), and HMG-CoA reductase and synthase (HMGR and HMGS) was significantly increased, and SREBP2 transcription was comparable in HCV-infected liver compared with normal liver. Positive correlations were found for LDLR versus HMGR, HMGR versus SREBP1c, and LDLR versus SREBP2 in the HCV-infected and control liver. Although the LXRα-SREBP1c-FASN pathway was upregulated, proteasome activator 28γ (PA28γ) was downregulated at the transcriptional level in HCV-infected liver, and was not significantly correlated with the other genes examined. The serum LDL cholesterol level was negatively correlated with LDLR and HMGR expression.


CONCLUSIONS
These results suggest that, in HCV-infected liver, the cholesterol load increases and cholesterol uptake is controlled, while de novo cholesterol synthesis is upregulated compared with the normal physiological state. The positive correlations in the expression levels of some cholesterol metabolism-associated genes indicate that not all of the metabolic pathways are dysregulated in HCV-infected liver.
Fujino
Tatsuya
T
Clinical Research Center, Kyushu Medical Center, National Hospital Organization, Japan.
Nakamuta
Makoto
M
Yada
Ryoko
R
Aoyagi
Yoko
Y
Yasutake
Kenichiro
K
Kohjima
Motoyuki
M
Fukuizumi
Kunitaka
K
Yoshimoto
Tsuyoshi
T
Harada
Naohiko
N
Yada
Masayoshi
M
Kato
Masaki
M
Kotoh
Kazuhiro
K
Taketomi
Akinobu
A
Maehara
Yoshihiko
Y
Nakashima
Manabu
M
Enjoji
Munechika
M