Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

Analysis of liver gene expression profile in male mice fed alcoholic (Lieber-Decarli's) diet and calorie-matched control diet for 6 weeks

ABSTRACT: Microarray analysis showed dysregulation of genes involved in lipid, xenobiotic and glutathione metabolism as well as those involved in mitochondrial function and cell proliferation in the livers of C57BL6 mice fed alcoholic liquid diet for 6 weeks. We analyzed liver RNA from 4 mice fed alcoholic diet and 4 mice fed control diet using the Affymetrix Mouse Exon 1.0 ST platform. Array data was processed by Affymetrix Exon Array Computational Tool.

ORGANISM(S): Mus musculus

SUBMITTER: kalpana ghoshal

PROVIDER: E-GEOD-30829 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Reduced susceptibility of DNA methyltransferase 1 hypomorphic (Dnmt1N/+) mice to hepatic steatosis upon feeding liquid alcohol diet.

Kutay Huban H Klepper Corie C Wang Bo B Hsu Shu-hao SH Datta Jharna J Yu Lianbo L Zhang Xiaoli X Majumder Sarmila S Motiwala Tasneem T Khan Nuzhat N Belury Martha M McClain Craig C Jacob Samson S Ghoshal Kalpana K

PloS one 20120808 8

<h4>Background</h4>Methylation at C-5 (5-mdC) of CpG base pairs, the most abundant epigenetic modification of DNA, is catalyzed by 3 essential DNA methyltransferases (Dnmt1, Dnmt3a and Dnmt3b). Aberrations in DNA methylation and Dnmts are linked to different diseases including cancer. However, their role in alcoholic liver disease (ALD) has not been elucidated.<h4>Methodology/principal findings</h4>Dnmt1 wild type (Dnmt1(+/+)) and hypomorphic (Dnmt1(N/+)) male mice that express reduced level of ...[more]

PMID: 22905112

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Project description:Background: Calorie restriction (CR) is the only intervention known to extend lifespan in a wide range of organisms, including mammals. However, the mechanisms by which it regulates mammalian aging remain largely unknown and the involvement of the TOR and Sirtuin pathways (which regulate aging in lower organisms) remain controversial. Femaleness is a second phenotype generally associated with longevity but the relationship between sex-biased and CR-induced gene expression remains undetermined. Methodology/Principal Findings: We generated microarray gene expression data from livers of male mice fed high calorie or CR diets, and we find that CR significantly changes the expression of over 3,000 genes, many between 10- and 50-fold. We compare our data to the GenAge database of known aging-related genes and to prior microarray expression data of genes expressed differently between male and female mice. CR generally feminizes gene expression and many of the most significantly changed individual genes are involved in aging, hormone signaling, and p53-associated regulation of the cell cycle and apoptosis. Among the genes showing the largest and most statistically significant CR-induced expression differences are Ddit4, a key regulator of the TOR pathway, and Nnmt, a regulator of lifespan linked to the Sirtuin pathway. Using Western analyses, we confirmed post-translational inhibition of the TOR pathway. Conclusions: Our data show that CR induces widespread gene expression changes and acts through highly evolutionarily conserved pathways, from microorganisms to mammals, and that its life-extension effects might arise partly from a shift toward a gene expression profile more typical of the longer-lived female sex. Keywords: Two-class gene expression comparison. Calorie restriction (CR) versus HIGH CALORIE feeding. Design of the experiment is a two-class paired design in which the two classes are HIGH CALORIE and CALORIE RESTRICTION (CR) dietary regimens fed to mice, resulting in 15 HIGH CALORIE microarrays and 8 CR microarrays; 23 total microarrays. Four HIGH CALORIE and 2 CR microarrays were produced using pools of 3 RNA samples for each microarray (6 pools of 3, plus 17 individual samples = 35 individual mouse liver samples, 23 microarrays). Total liver RNA was labeled directly. Reference RNA: Stratagene Universal Mouse Reference RNA.

Project description:To elucidate the effect of the polyphenols contained in alcoholic beverages on the metabolic stress induced by ethanol consumption, four groups of mice were fed for five weeks on Lieber's diet with or without ethanol, with ethanol plus ellagic acid, and with ethanol plus trans-resveratrol. Alcoholic fatty liver was observed in the group fed the ethanol diet but not in those fed the ethanol plus polyphenol diets. Liver transcriptome analysis revealed that the addition of the polyphenols suppressed the expression of the genes related to cell stress that were up-regulated by ethanol alone. Conversely, the polyphenols up-regulated the genes involved in bile acid synthesis, unsaturated fatty acid elongation, and tetrahydrofolate synthesis that were down-regulated by ethanol alone. Because parts of these genes were known to be regulated by the constitutive androstane receptor (CAR), we performed the same experiment in the CAR-deficient mice. As a result, fatty liver was observed not only in the ethanol group but also with the ethanol plus polyphenol groups. In addition, there was no segregation of the gene expression profiles among these groups. These results provide a molecular basis for the prevention of alcohol-induced stress by the polyphenols in alcoholic beverages. Five-week-old C3H/HeN female mice (CLEA, Japan) were acclimated to the maintenance condition (25Â°C, 8:00-20:00 day / 20:00-8:00 night cycle and 35~40 % humidity), fed a CE-2 diet (CLEA, Japan), and given water ad libitum for one week. Each group of mice (n=4 for wild type mice analysis and n=3 for CAR decficient mice analysis) was fed Lieber's isocaloric diet (Oriental yeast, Japan) containing water, containing ethanol, containing ethanol and ellagic acid (Fluka Biochemika, Switzerland), or containing ethanol and trans-resveratrol (Sigma, USA) (Supplementary Table 1) for one week at 10:00 ad libitum. Then, the mice were fed each diet at 12 g / day for four weeks (Supplementary Fig. 1A). The approximate intake of each polyphenol was 50 mg / kg body weight / day. At 10:00 of the final day of the experimental period, the animals were anesthetized by diethyl ether, sacrificed by cervial fracture, and the heart blood, and the liver were collected.

Dataset Information

Analysis of liver gene expression profile in male mice fed alcoholic (Lieber-Decarli's) diet and calorie-matched control diet for 6 weeks

Publications

Reduced susceptibility of DNA methyltransferase 1 hypomorphic (Dnmt1N/+) mice to hepatic steatosis upon feeding liquid alcohol diet.

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