Cide-a and Cide-c are induced in the progression of hepatic steatosis and inhibited by eicosapentaenoic acid.

Cide-a and Cide-c belong to the cell death-inducing DNA fragmentation factor-alpha-like effector family. Recent evidences suggest that these proteins may be involved in lipid accumulation in liver and adipose tissues. We confirmed that in the high-fat/high-sucrose diet-induced murine model of hepatic steatosis, the expression levels of the Cide-a and Cide-c genes were markedly and time-dependently increased, but returned to normal levels following improvement of hepatic steatosis by eicosapentaenoic acid (EPA) administration. Levels of expression of the Cide-a and Cide-c genes correlated well with plasma ALT. EPA inhibited the promoter activity of the Cide-a gene in vitro. Sterol regulatory element-binding protein-1 (SREBP-1) markedly enhanced the promoter activity of Cide-a, and EPA inhibited the expression of Cide-a mRNA. SREBP-1 and EPA did not affect those of Cide-c. These findings indicate that Cide-a and Cide-c are closely involved in the progression of hepatic steatosis, and that EPA inhibits Cide-a gene expression through SREBP-1 regulation.