Effects of atherogenic diet and atorvastatin treatment on gene expression profiles in the C57BL/6J mouse liver.
This study investigated the early and long-term effects of atherogenic diet on hepatic gene expression, and the restorative effects of atorvastatin in treating hypercholesterolemia. Two groups of female C57BL/6J mice were fed standard chow or atherogenic diet for 1-week early phase study and two other groups for 10 weeks. The fifth group had daily 10 mg/kg atorvastatin injections for 3 weeks from week 8 of the atherogenic diet. Gene expression profiling was carried out with Affymetrix GeneChips. One-week atherogenic diet elevated 38 and inhibited 127 gene expressions, while 10-week atherogenic diet elevated 165 and inhibited 281 genes by more than twofold. Atorvastatin could restore 78.2% and 68%, respectively, of the genes to normal levels. Genes in the Insig (insulin-induced gene)-SREBP (sterol regulatory element binding proteins) pathway were mostly inhibited by atherogenic diet at week 1 but elevated at week 10. Of these, 65.2% were restored by atorvastatin. In conclusion, lipid homeostatic mechanism coped well with short-term atherogenic diet. However, when such a diet was prolonged, the mechanism was no longer effective but entered into a pathological state in which lipogenic genes, especially those in the Insig-SREBP pathway, were upregulated. Atorvastatin could restore changes in the Insig-SREBP pathway that were induced by the atherogenic diet.
Zhao
Yulan
Y
Department of Paediatrics, Yong Loo Lin School of Medicine, National University of Singapore, Singapore.
Chan
Mei-Yen
MY
Zhou
Shuli
S
Heng
Chew-Kiat
CK
D000818:Animals; D000924:Anticholesteremic Agents / Q000494:pharmacology*; D000069059:Atorvastatin; D004036:Diet, Atherogenic; D005260:Female; D020869:Gene Expression Profiling; D006538:Heptanoic Acids / Q000494:pharmacology*; D050356:Lipid Metabolism; D008099:Liver / Q000187:drug effects / Q000502:physiology; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011758:Pyrroles / Q000494:pharmacology*; D051779:Sterol Regulatory Element Binding Proteins / Q000235:genetics / Q000378:metabolism
D000924:Anticholesteremic Agents; D006538:Heptanoic Acids; D011758:Pyrroles; D051779:Sterol Regulatory Element Binding Proteins; D000069059:Atorvastatin