Effects of dietary fat and oxidized cholesterol on gene expression in rat liver as assessed by cDNA expression array analysis.
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.


OBJECTIVE
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.


CONCLUSIONS
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.
Ringseis
Robert
R
Institut für Ernährungswissenschaften, Martin-Luther-Universität Halle-Wittenberg, Emil-Abderhalden-Strasse 26, 06108, Halle/Saale, Germany, eder@landw.uni-halle.de.
Eder
Klaus
K
D000818:Animals; D001205:Ascorbic Acid / Q000032:analysis / Q000097:blood; D001835:Body Weight; D002791:Cholesterol, Dietary / Q000494:pharmacology*; D000074263:Coconut Oil; D004041:Dietary Fats / Q000494:pharmacology*; D004042:Dietary Fats, Unsaturated / Q000494:pharmacology*; D005227:Fatty Acids / Q000032:analysis; D005395:Fish Oils; D005786:Gene Expression Regulation / Q000187:drug effects*; D005978:Glutathione / Q000032:analysis / Q000097:blood; D006888:Hydroxycholesterols / Q000032:analysis / Q000097:blood / Q000494:pharmacology; D008099:Liver / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism; D008297:Male; D020411:Oligonucleotide Array Sequence Analysis; D010713:Phosphatidylcholines / Q000737:chemistry; D010938:Plant Oils; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics; D051381:Rats; D017207:Rats, Sprague-Dawley; D020133:Reverse Transcriptase Polymerase Chain Reaction; D024502:alpha-Tocopherol / Q000032:analysis / Q000097:blood
D002791:Cholesterol, Dietary; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D005395:Fish Oils; D006888:Hydroxycholesterols; D010713:Phosphatidylcholines; D010938:Plant Oils; D011506:Proteins; C011724:cholest-5-en-3 beta,7 alpha-diol; C030341:salmon oil; D005978:Glutathione; D024502:alpha-Tocopherol; D001205:Ascorbic Acid; D000074263:Coconut Oil