Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

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Differential gene expression in lactating rats compared against age matched virgin controls

ABSTRACT: Gene level analysis of lactating day 10-11 16h Sprague-Dawley dams compared against age matched virgins. Lactation is a time of significantly increased energy demands imposed by the suckling young that requires a proportional adjustment in the ability of the lactating dam to absorb nutrients and to synthesize critical biomolecules to meet the dietary needs of both the offspring and the dam. We have shown an increase in the size and hydrophobicity of the bile acid pool during lactation [1], implying an increased absorption and disposition of lipids, sterols, nutrients, and xenobiotics. In order to investigate changes at the level of mRNA, we utilized an exon array and calculated gene level summaries to investigate changes in gene expression in the liver, duodenum, jejunum, and ileum of lactating dams when compared against age-matched virgin controls. Affymetrix Rat Exon 1.0ST arrays were used to determine expression of genes in the livers and small intestines of day 10-11 lactating Sprague Dawley rats and compared against virgins of comparable age.

ORGANISM(S): Rattus norvegicus

SUBMITTER: Mary Vore

PROVIDER: E-GEOD-19175 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Project description:Maternal obesity can program metabolic syndrome in offspring but the mechanisms are not well characterized. Moreover, the consequences of maternal overnutrition in the absence of frank obesity remain poorly understood. This study aimed to determine the effects of maternal consumption of a high fat-sucrose diet on the skeletal muscle metabolic and transcriptional profiles of adult offspring. Female Sprague Dawley rats were fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. Although maternal weights were not different between groups at conception or weaning, HFD dams were ~22% heavier than chow fed dams from mid-pregnancy until 4 days post-partum. Adult male offspring of HFD dams were not heavier than controls but demonstrated features of insulin resistance including elevated plasma insulin concentration (+40%, P<0.05). Next Generation mRNA Sequencing was used to identify differentially expressed genes in the soleus muscle of offspring, and Gene Set Enrichment Analysis (GSEA) to detect coordinated changes that are characteristic of a biological function. GSEA identified 15 pathways enriched for up-regulated genes, including cytokine signaling (P<0.005), starch and sucrose metabolism (P<0.017), and inflammatory response (P<0.024). A further 8 pathways were significantly enriched for down-regulated genes including oxidative phosphorylation (P<0.004) and electron transport (P<0.022). Western blots confirmed a ~60% reduction in the phosphorylation of the insulin signaling protein Akt (P<0.05) and ~70% reduction in mitochondrial complexes II (P<0.05) and V expression (P<0.05). On a normal diet, offspring of HFD dams developed an insulin resistant phenotype, with transcriptional evidence of muscle cytokine activation, inflammation and mitochondrial dysfunction. These data indicate that maternal overnutrition, even in the absence of pre-pregnancy obesity can promote metabolic dysregulation and predispose offspring to type 2 diabetes. Messenger RNA profile of skeletal muscle of male offspring from female Sprague Dawley rats fed either a diet rich in saturated fat and sucrose (HFD, 23.5% fat, 20% sucrose wt/wt) or a standard chow diet (NFD, 7% fat, 10% sucrose w/w) for the 3 weeks prior to mating and throughout pregnancy and lactation. There were 5 HFD samples compared to 6 NFD control samples.

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Differential gene expression in lactating rats compared against age matched virgin controls

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