title: Low doses of bisphenol A induce gene expression related to lipid synthesis and trigger triglyceride accumulation in adult mouse liver.
abstract: Changes in lifestyle are suspected to have strongly influenced the current obesity epidemic. Based on recent experimental, clinical, and epidemiological work, it has been proposed that some food contaminants may exert damaging effects on endocrine and metabolic functions, thereby promoting obesity and associated metabolic diseases such as nonalcoholic fatty liver disease (NAFLD). In this work, we investigated the effect of one suspicious food contaminant, bisphenol A (BPA), in vivo. We used a transcriptomic approach in male CD1 mice exposed for 28 days to different doses of BPA (0, 5, 50, 500, and 5,000 μg/kg/day) through food contamination. Data analysis revealed a specific impact of low doses of BPA on the hepatic transcriptome, more particularly on genes involved in lipid synthesis. Strikingly, the effect of BPA on the expression of de novo lipogenesis followed a nonmonotonic dose-response curve, with more important effects at lower doses than at the higher dose. In addition to lipogenic enzymes (Acc, Fasn, Scd1), the expression of transcription factors such as liver X Receptor, the sterol regulatory element binding protein-1c, and the carbohydrate responsive element binding protein that govern the expression of lipogenic genes also followed a nonmonotonic dose-response curve in response to BPA. Consistent with an increased fatty acid biosynthesis, determination of fat in the liver showed an accumulation of cholesteryl esters and of triglycerides.
  
  
  CONCLUSIONS
  Our work suggests that exposure to low BPA doses may influence de novo fatty acid synthesis through increased expression of lipogenic genes, thereby contributing to hepatic steatosis. Exposure to such contaminants should be carefully examined in the etiology of metabolic diseases such as NAFLD and nonalcoholic steatohepatitis.
authors.affiliation: INRA, TOXALIM (Research Centre in Food Toxicology), Toulouse, France.
authors.forename: Alice
authors.initials: A
authors.lastname: Marmugi
authors.forename: Simon
authors.initials: S
authors.lastname: Ducheix
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lasserre
authors.forename: Arnaud
authors.initials: A
authors.lastname: Polizzi
authors.forename: Alain
authors.initials: A
authors.lastname: Paris
authors.forename: Nathalie
authors.initials: N
authors.lastname: Priymenko
authors.forename: Justine
authors.initials: J
authors.lastname: Bertrand-Michel
authors.forename: Thierry
authors.initials: T
authors.lastname: Pineau
authors.forename: Hervé
authors.initials: H
authors.lastname: Guillou
authors.forename: Pascal G P
authors.initials: PG
authors.lastname: Martin
authors.forename: Laïla
authors.initials: L
authors.lastname: Mselli-Lakhal
mesh_terms: D000818:Animals; D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal / Q000008:administration & dosage*; D015870:Gene Expression / Q000187:drug effects*; D020869:Gene Expression Profiling; D007328:Insulin / Q000097:blood; D050356:Lipid Metabolism; D008055:Lipids / Q000096:biosynthesis*; D008099:Liver / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D020411:Oligonucleotide Array Sequence Analysis; D010636:Phenols / Q000008:administration & dosage*; D000098826:Bisphenol A Compounds
chemical_list: D001559:Benzhydryl Compounds; D004968:Estrogens, Non-Steroidal; D007328:Insulin; D008055:Lipids; D010636:Phenols; C006780:bisphenol A; D000098826:Bisphenol A Compounds