title: A biphasic response pattern of lipid metabolomics in the stage progression of hepatitis B virus X tumorigenesis.
abstract: Metabolic syndrome has closely linked to the development of human hepatocellular carcinoma (HCC). By using the hepatitis B virus (HBV) X (HBx) transgenic mouse model, we studied the dynamic evolution of serum and liver profiles of lipids and global cDNA expression at different stages of HBx tumorigenesis. We observed that the lipid (triglycerides, cholesterol, and fatty acids) profiles revealed a biphasic response pattern during the progression of HBx tumorigenesis: a small peak at early phase and a large peak or terminal switch at the tumor phase. By analyzing cDNA microarray data, the early peak correlated to the oxidative stress and pro-inflammatory response, which then resolved at the middle phase and were followed by the terminal metabolic switch in the tumor tissues. Five lipid metabolism-related genes, the arachidonate 5-lipoxygenase, lipoprotein lipase, fatty acid binding protein 4, 1-acylglycerol-3-phosphate O-acyltransferase 9, and apolipoprotein A-IV were identified to be significantly activated in HBx transgenic HCCs and further validated in human HBV-related HCCs. Inhibition of these lipid genes could reverse the effect of HBx on lipid biosynthesis and suppress HBx-induced cell proliferation in vitro. Our results support the concept that metabolic syndrome plays an important role in HBV tumorigenesis. The dysregulation of lipid metabolic genes may predict the disease progression to HCC in chronic hepatitis B patients.
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Chiao-Fang
authors.initials: CF
authors.lastname: Teng
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Wen-Chuan
authors.initials: WC
authors.lastname: Hsieh
authors.affiliation: Institute of Basic Medical Research, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Ching-Wen
authors.initials: CW
authors.lastname: Yang
authors.affiliation: Department of Physiology, National Taiwan University College of Medicine, Taipei, Taiwan.
authors.forename: Hui-Min
authors.initials: HM
authors.lastname: Su
authors.affiliation: Department of Life Sciences and Institute of Genome Sciences, National Yang-Ming University, Taipei, Taiwan.|Institute of Molecular and Genomic Medicine, National Health Research Institutes, Zhunan, Taiwan.
authors.forename: Ting-Fen
authors.initials: TF
authors.lastname: Tsai
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.
authors.forename: Wang-Chou
authors.initials: WC
authors.lastname: Sung
authors.affiliation: Department of Medical Laboratory Science and Biotechnology, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Wenya
authors.initials: W
authors.lastname: Huang
authors.affiliation: National Institute of Infectious Diseases and Vaccinology, National Health Research Institutes, Tainan, Taiwan.|Institute of Basic Medical Research, National Cheng Kung University College of Medicine, Tainan, Taiwan.
authors.forename: Ih-Jen
authors.initials: IJ
authors.lastname: Su
mesh_terms: D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D049109:Cell Proliferation; D002472:Cell Transformation, Viral / Q000235:genetics; D004195:Disease Models, Animal; D018450:Disease Progression; D005227:Fatty Acids / Q000097:blood / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008099:Liver / Q000378:metabolism / Q000473:pathology; D008113:Liver Neoplasms / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D051379:Mice; D008822:Mice, Transgenic; D009367:Neoplasm Staging; D015534:Trans-Activators / Q000235:genetics*; D054334:Viral Regulatory and Accessory Proteins
chemical_list: D005227:Fatty Acids; D008055:Lipids; D015534:Trans-Activators; D054334:Viral Regulatory and Accessory Proteins; C057628:hepatitis B virus X protein
keywords: cholesterol; fatty acids; hepatocellular carcinoma; metabolic syndrome; triglycerides