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“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 NVP-LDE225 cost 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 PF-02341066 chemical structure 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. Conclusion: 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. (Hepatology 2012) Changes in diet and lifestyle are leading causes for the emergence of the metabolic diseases associated with obesity. Recently, the hypothesis that a number of food contaminants acting as endocrine-disrupting chemicals may influence metabolic diseases has been proposed.1 Bisphenol A (BPA) is an endocrine disruptor highly prevalent in our environment. It is used as the monomer of polycarbonate plastics and epoxy resins.2 The human population is widely exposed to low see more levels of BPA, primarily by way of the diet by migration from food and beverage containers.2 93% of urine samples collected from the National Health and Nutrition Examination Survey (NHANES III) cohort revealed detectable levels of BPA.3 As a protective measure the U.S. Environmental Protection Agency and the European Food Safety Agency have established a tolerable daily intake (TDI) of 50 μg/kg/day derived by applying an uncertainty factor of 100 to the no-observed-adverse-effect level (NOAEL) of 5,000 μg/kg/day mainly based on liver and reproductive toxicity.