A subset of dysregulated metabolic and survival genes is associated with severity of hepatic steatosis in obese Zucker rats

• DOI: 10.1194/jlr.m001966
• Publication Date: 2009-09-26T00:17:48Z
• Authors: Xabier Buqué; María José Martínez; Ainara Cano; María E. Miquilen...; Carmelo García-Mo...; Patricia Aspichueta; Begoña Ochoa
• Keywords: Lipogenesis; Steatosis; CD36; Steatohepatitis

We aimed to characterize the primary abnormalities associated with fat accumulation and vulnerability hepatocellular injury of obesity-related fatty liver. performed functional analyses comparative transcriptomics isolated hepatocytes from livers obese insulin-resistant Zucker rats (comprising mild severe hepatic steatosis) age-matched lean littermates, searching for novel genes linked chronic steatosis. Of tested genome, 1.6% was identified as steatosis linked. Overexpressed were mainly dedicated metabolism (100%), signaling, defense/acute phase (approximately 70%); detoxification, steroid, sulfur 65%) well cell growth/proliferation protein synthesis/transformation 70%) downregulated. The overexpression key involved in de novo lipogenesis, acid glycerolipid import synthesis, acetyl-CoA cofactor provision paralleled by enhanced lipogenesis production large triacylglycerol-rich VLDL. Greatest changes gene expression seen those encoding lipogenic malic enzyme (up 7-fold increased) cell-to-cell interacting cadherin 17 8-fold decreased). Among validated genes, synthase, stearoyl-CoA desaturase 1, translocase/Cd36, enzyme, cholesterol-7 alpha hydroxylase, 17, peroxisome proliferator-activated receptor significantly correlated severity In conclusion, dysregulated metabolic survival accompany may render steatotic more vulnerable progressive nonalcoholic liver disease.