Altered expression patterns of lipid metabolism genes in an animal model of HCV core-related, nonobese, modest hepatic steatosis.
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-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.


CONCLUSIONS
Some genes of lipid metabolism, mitochondrial function, and immune reaction and the SREBP pathway are involved in HCV core-related, nonobese, modest hepatic steatosis.
Chang
Ming-Ling
ML
Liver Research Center and Department of Hepatogastroenterology, Chang Gung Memorial Hospital, No 5, Fu Hsing Street, Kuei Shan, Taoyuan, Taiwan. mlchang8210@gmail.com
Yeh
Chau-Ting
CT
Chen
Jeng-Chang
JC
Huang
Chau-Chun
CC
Lin
Shi-Ming
SM
Sheen
I-Shyan
IS
Tai
Dar-In
DI
Chu
Chia-Ming
CM
Lin
Wei-Pin
WP
Chang
Ming-Yu
MY
Liang
Chun-Kai
CK
Chiu
Cheng-Tang
CT
Lin
Deng-Yn
DY
D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D005234:Fatty Liver / Q000097:blood / Q000235:genetics*; D020869:Gene Expression Profiling; D007150:Immunohistochemistry; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism / Q000235:genetics*; D008055:Lipids / Q000097:blood; D051379:Mice; D008822:Mice, Transgenic; D020411:Oligonucleotide Array Sequence Analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics; D014758:Viral Core Proteins / Q000235:genetics* / Q000378:metabolism
D001786:Blood Glucose; D007328:Insulin; D008055:Lipids; D051779:Sterol Regulatory Element Binding Proteins; D014758:Viral Core Proteins; C069130:nucleocapsid protein, Hepatitis C virus