Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Hepatic expression data between C57BL/6J and DBA/2J mice

ABSTRACT: C57BL/6J (B6) and DBA/2J (D2) mice were fed a high-fat/high-cholesterol diet in order to investigate the responses to that diet over time and their underlying genetic factors. We observed distinctly diverse responses between B6 and D2 mice, including dynamic distribution of cholesterol in serum and bile, hepatic apoptosis and dynamic formation of gallstones and atherosclerosis. Hepatic microarray analysis revealed distinctly different gene expression patterns in functional pathway groups including lipid metabolism, oxidative stress, immune/inflammation response and apoptosis, which might account for the different responses.This might provide us not only new insights into gallstones formation and atherosclerosis, but also opportunities to identify candidate genes for high-fat/high-cholesterol related diseases. C57BL/6J (B6) and DBA/2J (D2) mice were fed a high-fat/high-cholesterol diet in 0,1,4 12,21 weeks,respectively. Liver tissues of mice from each time-point were removed for RNA extraction. Equal amounts of RNA samples from five mice of each strain at each time-point were pooled and then used to generate biotinylated cRNA targets for Affymetrix GeneChip Mouse Genome 430 2.0 Array.

ORGANISM(S): Mus musculus

SUBMITTER: Mingzhe Zhu

PROVIDER: E-GEOD-17810 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:High-fat diets are associated with increased obesity and metabolic disease in mice and humans. Here we used analysis of variance (ANOVA) to scrutinize a microarray data set consisting of 10 inbred strains of mice from both sexes fed atherogenic high-fat and control chow diets. An overall F-test was applied to the 40 unique groups of strain-diet-sex to identify 15,288 genes with altered transcription. Bootstrapping k-means clustering separated these changes into four strain-dependent expression patterns, including two sex-related profiles and two diet-related profiles. Sex-induced effects correspond to secretion (males) or fat and energy metabolism (females), whereas diet-induced changes relate to neurological processes (chow) or immune response (high-fat). The full set of pairwise contrasts for differences between strains within sex (90 different statistical tests) uncovered 32,379 total changes. These differences were unevenly distributed across strains and between sexes, indicating that strain-specific responses to high-fat diet differ between sexes. Correlations between expression levels and 8 obesity-related traits identified 5,274 associations between transcript abundance and measured phenotypic endpoints. From this number, 2,678 genes are positively correlated with total cholesterol levels and associate with immune-related categories while 2,596 genes are negatively correlated with cholesterol and connect to cholesterol synthesis. Keywords: gene expression analysis, strain comparision, effect of dietary fat, sex-specific effects One group of mice was fed an atherogenic high-fat (30% fat) diet containing cholic acid to increase fat uptake and another was fed a low-fat (6% fat) regular chow diet. Males and females from both diets were studied for mouse strains 129S1/SvImJ, A/J, BALB/cJ, C3H/HeJ, C57BL/6J, CAST/EiJ, DBA/2J, I/LnJ, MRL/MpJ-Tnfrsf6lpr/J, NZB/BINJ, PERA/Ei, and SM/J. All strains were sacrificed between 11- and 13 weeks of age except for CAST and PERA, which were harvested after 50 weeks of age. CAST and PERA were subsequently removed from our analysis based on discrepant harvest age, but can be found in our database (see below). Three replicate animals were used for each combination of diet, strain, and sex, resulting in a total of 120 mice surveyed for gene expression.

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Hepatic expression data between C57BL/6J and DBA/2J mice

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