Basic–liver, pancreas, and biliary tractHepatitis B Virus X Protein Induces Hepatic Steatosis Via Transcriptional Activation of SREBP1 and PPARγ
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Transgenic Animals
The production of HBx transgenic mice used in this study already has been reported.19 Briefly, we generated HBx homozygous (+/+) transgenic mice by mating HBx heterozygous transgenic mice to each other. To generate HBx homozygous transgenic mice on mixed-background of C57BL/6 and CBA strains, HBx homozygous mice on C57BL/6 mice were crossed with CBA wild-type mice. The heterozygous transgenic offspring with a mixed background of C57BL/6 and CBA strains were mated between them. Among their
Overexpression of HBx Induces Lipid Accumulation in HepG2 and HBx-Transgenic Mice
To investigate the effects of HBx protein on hepatic lipid accumulation, we examined the hepatic lipid content in the liver tissues of HBx-transgenic mice. The livers of 11-week-old HBx-transgenic mice were enlarged and light-colored (Figure 1A). The liver weight per body weight of HBx mice was increased 2-fold compared with the wild-type mice at the same age (Figure 1B). We examined histologic changes of the liver of HBx-transgenic mice. The H&E-stained liver sections of HBx-transgenic mice
Discussion
Increasing evidence indicates that hepatic lipid accumulation is related to hepatic fibrosis, inflammation, apoptosis, and cancer.3, 4 In particular, it is assumed that lipid accumulation is a prerequisite for subsequent events leading to liver injury in nonalcoholic fatty liver disease.31 In addition, it recently was shown that hepatic steatosis may be a more vulnerable factor in HCV-induced liver pathogenesis3 and may impair the response of interferon-based therapy.32, 33 Because of the
References (59)
- et al.
Hepatic steatosis in chronic hepatitis B and C: predictors, distribution and effect on fibrosis
J Hepatol
(2005) - et al.
The hepatitis B virus X protein inhibits secretion of apolipoprotein B by enhancing the expression of N-acetylglucosaminyltransferase III
J Biol Chem
(2004) - et al.
SREBP-1, a basic-helix-loop-helix-leucine zipper protein that controls transcription of the low density lipoprotein receptor gene
Cell
(1993) - et al.
SREBP-1, a membrane-bound transcription factor released by sterol-regulated proteolysis
Cell
(1994) - et al.
Stimulation of adipogenesis in fibroblasts by PPAR gamma 2, a lipid-activated transcription factor
Cell
(1994) - et al.
Liver peroxisome proliferator-activated receptor gamma contributes to hepatic steatosis, triglyceride clearance, and regulation of body fat mass
J Biol Chem
(2003) - et al.
Adipocyte-specific gene expression and adipogenic steatosis in the mouse liver due to peroxisome proliferator-activated receptor gamma1 (PPARgamma1) overexpression
J Biol Chem
(2003) - et al.
Altered constitutive expression of fatty acid-metabolizing enzymes in mice lacking the peroxisome proliferator-activated receptor alpha (PPARalpha)
J Biol Chem
(1998) - et al.
Incidence of hepatocellular carcinoma in transgenic mice expressing the hepatitis B virus X-protein
J Hepatol
(1999) - et al.
Sterol regulation of fatty acid synthase promoterCoordinate feedback regulation of two major lipid pathways
J Biol Chem
(1995)
Hepatitis B virus X protein regulates transactivation activity and protein stability of the cancer-amplified transcription coactivator ASC-2
Hepatology
Functional interaction of bZIP proteins and the large subunit of replication factor C in liver and adipose cells
J Biol Chem
Regulation of activating transcription factor-2 in early stage of the adipocyte differentiation program
Biochem Biophys Res Commun
The hepatitis B virus-X protein activates a phosphatidylinositol 3-kinase-dependent survival signaling cascade
J Biol Chem
Steatosis in chronic hepatitis C: can weight reduction improve therapeutic efficacy?
J Hepatol
KGF induces lipogenic genes through a PI3K and JNK/SREBP-1 pathway in H292 cells
J Lipid Res
ADD1/SREBP-1c mediates insulin-induced gene expression linked to the MAP kinase pathway
Biochem Biophys Res Commun
Regulatory role of glycogen synthase kinase 3 for transcriptional activity of ADD1/SREBP1c
J Biol Chem
CYP2E1: from ASH to NASH
Hepatol Res
In situ detection of lipid peroxidation and oxidative DNA damage in non-alcoholic fatty liver diseases
J Hepatol
Mitochondrial adaptations to obesity-related oxidant stress
Arch Biochem Biophys
Hepatitis B virus X protein induces cell death by causing loss of mitochondrial membrane potential
J Biol Chem
Human hepatitis B virus-X protein alters mitochondrial function and physiology in human liver cells
J Biol Chem
Hepatitis B virus X protein induced expression of interleukin 18 (IL-18): a potential mechanism for liver injury caused by hepatitis B virus (HBV) infection
J Hepatol
Impaired expression of the peroxisome proliferator-activated receptor alpha during hepatitis C virus infection
Gastroenterology
Chronic hepatitis B
N Engl J Med
Steatosis: co-factor in other liver diseases
Hepatology
Hepatic steatosis is a risk factor for hepatocellular carcinoma in patients with chronic hepatitis C virus infection
Cancer
cDNA microarray analysis of HBV transgenic mouse liver identifies genes in lipid biosynthetic and growth control pathways affected by HBV
J Med Virol
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Supported by the Korean Ministry of Health and Welfare, Republic of Korea (A050404), and the 21st century Frontier Program in the Functional Human Genome Project of Korea (HGC0300526).
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K.H.K. and H.-J.S. contributed equally to this work.