Dataset Information

Effects of atherogenic diet and atorvastatin treatment on gene expression profiles in the C57BL/6J mouse liver.

ABSTRACT: 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.

SUBMITTER: Zhao Y

PROVIDER: S-EPMC6042009 | biostudies-literature | 2008

REPOSITORIES: biostudies-literature

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Effects of atherogenic diet and atorvastatin treatment on gene expression profiles in the C57BL/6J mouse liver.

Zhao Yulan Y Chan Mei-Yen MY Zhou Shuli S Heng Chew-Kiat CK

Gene expression 20080101 3

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. ...[more]

PMID: 18590051

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Project description:BackgroundAlcohol addiction develops through a series of stages, and mechanistic studies are needed to understand the transition from initial drug use to sustained controlled alcohol consumption followed by abuse and physical dependence. The focus of this study was to examine the effects of voluntary alcohol consumption on brain gene expression profiles using a mouse model of binge drinking. The main goal was to identify alcohol-responsive genes and functional categories after a single episode of drinking to intoxication.MethodsWe used a modification of a "Drinking In the Dark" (DID) procedure (Rhodes et al., 2005) that allows mice to experience physiologically relevant amounts of alcohol in a non-stressful environment and also allows for detection of alcohol-sensitive molecular changes in a dose-dependent manner. C57BL/6J male mice were exposed to either 20% ethanol solution or water (single bottle) starting 3 hours after lights off for 4 hours and brains were harvested immediately after the drinking session. cDNA microarrays were used to assess the effects of voluntary drinking on global gene expression in 6 brain regions. We employed three statistical approaches to analyze microarray data.ResultsA commonly used approach that applies a strict statistical threshold identified the eight top statistically significant genes whose expression was significantly correlated with blood ethanol concentration (BEC) in one of the brain regions. We then used a systems network approach to examine brain region-specific transcriptomes and identify modules of co-expressed (correlated) genes. In each brain region, we identified alcohol-responsive modules, i.e., modules significantly enriched for genes whose expression was correlated with BEC. A functional over-representation analysis was then applied to examine the organizing principles of alcohol-responsive modules. Genes were clustered into modules according to their roles in different physiological processes, functional groups, and cell types, including blood circulation, signal transduction, cell-cell communication, and striatal neurons. Finally, a meta-analysis across all brain regions suggested a global role of increasing alcohol dose in coordination of brain blood circulation and reaction of astrocytes.ConclusionsThis study showed that acute drinking resulted in small but consistent changes in brain gene expression which occurred in a dose-dependent manner. We identified both general and region-specific changes, some of which represent adaptive changes in response to increasing alcohol dose, which may play a role in alcohol-related behaviours, such as tolerance and consumption. Our systems approach allowed us to estimate the functional values of individual genes in the context of their genetic networks and formulate new refined hypotheses. An integrative analysis including other alcohol studies suggested several top candidates for functional validation, including Mt2, Gstm1, Scn4b, Prkcz, and Park7.

Dataset Information

Effects of atherogenic diet and atorvastatin treatment on gene expression profiles in the C57BL/6J mouse liver.

Publications

Effects of atherogenic diet and atorvastatin treatment on gene expression profiles in the C57BL/6J mouse liver.

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