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- Title
Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis.
- Authors
Ming-Ling Chang; Chau-Ting Yeh; Jeng-Chang Chen; Chau-Chun Huang; Shi-Ming Lin; I-Shyan Sheen; Dar-In Tai; Chia-Ming Chu; Wei-Pin Lin; Ming-Yu Chang; Chun-Kai Liang; Cheng-Tang Chiu; Deng-Yn Lin
- Abstract
Background: Because the gene expression patterns of nonobese hepatic steatosis in affected patients remain unclear, we sought to explore these patterns using an animal model of nonobese hepatic steatosis. Methods: We developed mice that conditionally express the hepatitis C virus (HCV) core protein regulated by the tetracycline transactivator (tTA). Microarray analyses and reverse-transcription polymerase chain reaction were performed using liver samples of both the double transgenic mice (DTM), which express both the HCV core and tTA, and single transgenic mice (STM), which express tTA alone, at 2 months of age. Functional categories of genes with altered expression were classified using gene ontology programs. Serum glucose, lipid levels, and systemic blood pressure were also measured. Results: Approximately 20-30% of hepatocytes from the DTM were steatotic. No significant differences were observed in the serum glucose, lipid content, or blood pressure levels between the DTM and STM. Gene expression analyses revealed Sterol-regulatory element-binding protein (SREBP) pathway activation and dysregulation of the following genes involved in lipid metabolism: 3-hydroxy-3-methylglutarylcoenzyme A synthase 1, Apolipoprotein AII, Apolipoprotein CI, acyl-CoA thioesterase I, and fatty acid binding protein 1; in mitochondrial function: solute carrier family 25 member 25 and cytochrome c oxidase subunit II; in immune reaction: complement component 3, lymphocyte antigen 6 complex, locus A, lymphocyte antigen 6 complex, locus C, lymphocyte antigen 6 complex, locus D, and lymphocyte antigen 6 complex, locus E. Conclusion: Some genes of lipid metabolism, mitochondrial function, and immune reaction and the SREBP pathway are involved in HCV core-related, nonobese, modest hepatic steatosis.
- Subjects
GENE expression; METABOLIC regulation; ANIMAL genetics; HEPATITIS C virus; FATTY degeneration; TETRACYCLINE; TRANSGENIC mice; LIVER cells
- Publication
BMC Genomics, 2008, Vol 9, p1
- ISSN
1471-2164
- Publication type
Article
- DOI
10.1186/1471-2164-9-109