Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis
1 Liver Research Center and Department of Hepatogastroenterology, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan; Chang Gung University, College of Medicine, Taoyuan, Taiwan
2 Department of Surgery, Chang Gung Memorial Hospital, Taoyuan, Taiwan
3 Division of Endocrinology & Metabolism, Department of Internal Medicine, Chang Gung Memorial Hospital, Taipei, Taiwan
4 Division of Pediatric Critical Care and Emergency Medicine, Chang Gung Memorial Hospital, Taoyuan, Taiwan
BMC Genomics 2008, 9:109 doi:10.1186/1471-2164-9-109Published: 29 February 2008
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.
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.
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-methylglutaryl-coenzyme 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.
Some genes of lipid metabolism, mitochondrial function, and immune reaction and the SREBP pathway are involved in HCV core-related, nonobese, modest hepatic steatosis.