Background   

Specific oxysterols acting as ligands for nuclear transcription factors were shown to affect expression of genes involved in lipid metabolism. However, the various biological effects of oxysterols such as cytotoxicity, atherogenicity or mutagenicity suggest that other genes may be also affected by oxysterols than lipid metabolism.

Aim of the study   

The present study was conducted to investigate the effects of dietary oxidized cholesterol containing significant amounts of oxysterols and its interactions with different dietary fats on gene expression profiles as assessed by DNA array technology in rats.

Methods   

54 male Sprague–Dawley rats were assigned to six groups and were fed six semisynthetic diets, which varied in the type of dietary fat (coconut oil vs. salmon oil) and dietary cholesterol (none cholesterol vs. 5 g unoxidized cholesterol/kg vs. 5 g oxidized cholesterol/kg).

Results   

Changes in gene expression as observed in response to dietary oxidized cholesterol were strongly dependent on the type of fat. In the rats fed coconut oil, the expression of 7 genes (5 up– and 2 down–regulated) was altered by dietary oxidized cholesterol, while in the rats fed salmon oil, the expression of 50 genes (16 up– and 34 down–regulated) was altered. 29 genes (22 up- and 7 down–regulated) were identified as possible targets for an altered gene expression by dietary salmon oil as compared to dietary coconut oil.

Conclusion   

The present study showed that dietary oxidized cholesterol transcriptionally affects many genes involved in xenobiotic metabolism and stress response—an effect that was amplified by the administration of fish oil as dietary fat.