Abstract
BackgroundBecause 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.MethodsWe 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.ResultsApproximately 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.ConclusionSome genes of lipid metabolism, mitochondrial function, and immune reaction and the SREBP pathway are involved in HCV core-related, nonobese, modest hepatic steatosis.
Highlights
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 aimed to study the gene expression involved in lipid metabolism of an animal model of nonobese hepatic steatosis free from metabolic syndrome based on the conditional hepatitis C virus (HCV) core transgenic mice developed from our previous work
We developed an animal model of nonobese hepatic steatosis with the transgenic expression of the HCV core protein
Summary
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. The basis for nonobese hepatic steatosis remains uncertain, for those who lack any metabolic syndromes. Cholesterol-fed rabbits share several physiopathological features of NAFLD, like hyperlipidemia, but are devoid of insulin resistance or obesity [3]; while overexpression of SREBP-1a in spontaneously hypertensive rat models were nonobese animals with hypertension, hepatic steatosis, and the metabolic syndrome [4]. Whether the basis of the "uncomplicated" nonobese hepatic steatosis is similar to hepatic steatosis complicated by obesity and/or metabolic syndrome remains unresolved. We aimed to study the gene expression involved in lipid metabolism of an animal model of nonobese hepatic steatosis free from metabolic syndrome based on the conditional HCV core transgenic mice developed from our previous work. Liver from the 2 month old conditional HCV core transgenic mice on chow without doxycycline (dox) showed that the severity of hepatic steatosis correlated with HCV core expression, peaked at the age of 2 months but diminished gradually [6]
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