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Hepatic Gene Expression Changes in Diethynitrosamin-initiated and Cholic Acid promoted tumors

ABSTRACT: Mice were fed with either normal diet (ND), 0.2% cholic acid diet (0.2%CA), DEN treated and fed ND or DEN treated and fed 0.2%CA diet. DEN was treated at 15 microgram/kg body weight at postnatal day 15. Diets were fed for two months starting 8 months of age till 10 months of age. Livers were collected at10 months of age, Total RNA was isolated and used for microarray experiments.

ORGANISM(S): Mus musculus

PROVIDER: GSE75445 | GEO | 2016/08/10

SECONDARY ACCESSION(S): PRJNA304304

REPOSITORIES: GEO

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Project description:To determine the effects of age and lipoic acid supplementation on hepatic gene expression, we fed young (3 months) and old (24 months) male Fischer 344 rats a diet with or without 0.2% (w/w) R-?-lipoic acid (LA) for two weeks. Total RNA isolated from liver tissue was analyzed by Affymetrix microarray to examine changes in transcriptional profile. Results showed an increase in pro-inflammatory gene expression in the aging liver, with increased immune cell function and tissue remodeling genes, representing 45% of the age-related transcriptome changes. Increased inflammation was corroborated by increases in soluble ICAM1 levels with age. There were also observed age-related increases in transcription of genes related to lipid and cholesterol synthesis including Acetyl CoA Carboxylase (Acacb) and Fatty acid Synthase (Fasn). Supplementation of old animals with LA did not reverse this necro-inflammatory phenotype, yet limited age-associated hepatic dyslipidemia. Dietary LA further affected a small but concerted number of hepatic genes regardless of age. These included declines in lipid and bile synthesis genes. Decline in lipid synthesis genes was further corroborated by a decrease in Fasn and Acc protein levels. Intriguingly, LA also altered the expression of genes governing circadian rhythm, most notably Bmal1, Npas2, and Per2, which changed in a coordinated manner with respect to their rhythmic transcription. Thus, advanced age is associated with a necro-inflammatory phenotype and increased lipid synthesis, while chronic LA supplementation influences hepatic genes associated with energy metabolism and circadian rhythm regardless of age. Young (3 months) and old (24 months) Fischer 344 male rats were fed an AIN-93M diet ± 0.2% (w/w) R-?-lipoic acid for two weeks prior to sacrifice. Total RNA was extracted from the median lobe of the liver and analyzed using Affymetrix Rat Genome 230 2.0 Genechips. There were hybridizations for 8 animals in each of the young control, young LA-supplemented, and old control groups, and 6 animals in the old LA-supplemented group. There are only 6 animals in the old LA group because two animals died during the two-week feeding period. This is the reason for nonsequential numbering of animals in this group.

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Hepatic Gene Expression Changes in Diethynitrosamin-initiated and Cholic Acid promoted tumors

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