文章基本信息

标题：A subset of dysregulated metabolic and survival genes is associated with severity of hepatic steatosis in obese Zucker rats
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作者：Xabier Buqué ; María José Martínez ; Ainara Cano 等
期刊名称：JLR Papers In Press
印刷版ISSN：0022-2275
电子版ISSN：1539-7262
出版年度：2010
卷号：51
期号：3
页码：500-513
DOI：10.1194/jlr.M001966
语种：English
出版社：American Society for Biochemistry and Molecular Biology
摘要：We aimed to characterize the primary abnormalities associated with fat accumulation and vulnerability to hepatocellular injury of obesity-related fatty liver. We performed functional analyses and comparative transcriptomics of isolated primary hepatocytes from livers of obese insulin-resistant Zucker rats (comprising mild to severe hepatic steatosis) and age-matched lean littermates, searching for novel genes linked to chronic hepatic steatosis. Of the tested genome, 1.6% was identified as steatosis linked. Overexpressed genes were mainly dedicated to primary metabolism (100%), signaling, and defense/acute phase (∼70%); detoxification, steroid, and sulfur metabolism (∼65%) as well as cell growth/proliferation and protein synthesis/transformation (∼70%) genes were downregulated. The overexpression of key genes involved in de novo lipogenesis, fatty acid and glycerolipid import and synthesis, as well as acetyl-CoA and cofactor provision was paralleled by enhanced hepatic lipogenesis and production of large triacylglycerol-rich VLDL. Greatest changes in gene expression were seen in those encoding the lipogenic malic enzyme (up to 7-fold increased) and cell-to-cell interacting cadherin 17 (up to 8-fold decreased). Among validated genes, fatty acid synthase, stearoyl-CoA desaturase 1, fatty acid translocase/Cd36, malic enzyme, cholesterol-7α hydroxylase, cadherin 17, and peroxisome proliferator-activated receptor α significantly correlated with severity of hepatic steatosis. In conclusion, dysregulated expression of metabolic and survival genes accompany hepatic steatosis in obese insulin-resistant rats and may render steatotic hepatocytes more vulnerable to cell injury in progressive nonalcoholic fatty liver disease.
关键词：gene expression ; lipid synthesis ; triglyceride secretion