PolySearch2 - Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis.

PolySearch2 - Result Details

(2015) Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis. Toxicology and applied pharmacology;Toxicol. Appl. Pharmacol.;2015 Apr;284(2):101-12

Developmental Bisphenol A (BPA) exposure increases adulthood hepatic steatosis with reduced mitochondrial function. To investigate the potential epigenetic mechanisms behind developmental BPA-induced hepatic steatosis, pregnant Sprague-Dawley rats were dosed with vehicle (oil) or BPA (100I1/4g/kg/day) from gestational day 6 until postnatal day (PND) 21. After weaning, offspring were either challenged with a high-fat (HF; 45 % fat) or remained on a control (C) diet until PND110. From PND60 to 90, both BPA and HF diet increased the fat/lean ratio in males only, and the combination of BPA and HF diet appeared to cause the highest ratio. On PND110, Oil-HF, BPA-C, and BPA-HF males had higher hepatic lipid accumulation than Oil-C, with microvesicular steatosis being marked in the BPA-HF group. Furthermore, on PND1, BPA increased and modified hepatic triglyceride (TG) and free fatty acid (FFA) compositions in males only. In PND1 males, BPA increased hepatic expression of FFA uptake gene Fat/Cd36, and decreased the expression of TG synthesis- and I2-oxidation-related genes (Dgat, Agpat6, CebpI+-, CebpI2, Pck1, Acox1, Cpt1a, Cybb). BPA altered DNA methylation and histone marks (H3Ac, H4Ac, H3Me2K4, H3Me3K36), and decreased the binding of several transcription factors (Pol II, C/EBPI2, SREBP1) within the male Cpt1a gene, the key I2-oxidation enzyme. In PND1 females, BPA only increased the expression of genes involved in FFA uptake and TG synthesis (Lpl, Fasn, and Dgat). These data suggest that developmental BPA exposure alters and reprograms hepatic I2-oxidation capacity in males, potentially through the epigenetic regulation of genes, and further alters the response to a HF diet.

MEDLINE 25748669 : Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis.

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Legend

Query Term

Association Word

Drug, Toxin

Gene, Protein, Gene Family, Pathway, SNP

Human Metabolite, Food Metaboilte, MeSH Compound

Tissue, Organ, Subcellular Localization

MeSH Term, Gene Ontology, Chemical Taxonomy, ICD-10 Code

Health Effect, Drug Effect, Adverse Effect

Disease, Species

Please cite:

Liu Y., Liang Y., Wishart D.S. (2015) PolySearch 2.0: A significantly improved text-mining system for discovering associations between human diseases, genes, drugs, metabolites, toxins, and more. Nucleic Acids Res. 2015 Jul 1;43(Web Server Issue):W535-42.

To cite the original version of PolySearch (no longer active), please cite:

Cheng D., Knox C., Young N., Stothard P., Damaraju S., Wishart D.S. (2008) PolySearch: a web-based text mining system for extracting relationships between human diseases, genes, mutations, drugs and metabolites. Nucleic Acids Res. 2008 Jul 1;36(Web Server Issue):W399-405.

This project is supported by the Canadian Institutes of Health Research (award #111062), Alberta Innovates - Health Solutions, and by The Metabolomics Innovation Centre (TMIC), a nationally-funded research and core facility that supports a wide range of cutting-edge metabolomic studies. TMIC is funded by Genome Alberta, Genome British Columbia, and Genome Canada, a not-for-profit organization that is leading Canada's national genomics strategy with $900 million in funding from the federal government.