The effect of perinatal exposure to the endocrine disruptor bisphenol-a on metabolism and the development of diet-induced obesity in adulthood

H.A. MacKay, D. Tsirlin, S. Patel, Z. Patterson, R. Khazall, A. Abizaid

Bisphenol-A (BPA) is a component of polycarbonate plastic, epoxy resins, and is commonly found in food and drink containers. Owing to its ubiquity in the environment and its status as an endocrine disrupting chemical (EDC), continual exposure to low doses of BPA leeched from its various sources has recently become a source of concern. Of particular interest here is the possibility that low-dose exposure to BPA contributes to the development of obesity. Here, we investigate the effect of early life exposure to BPA on metabolic parameters and the development of obesity in adult life. Female CD-1 mice maintained on a purified diet were mated and placed on one of the following ecologically relevant diets through to weaning: 1 µg/kg/diet BPA (low dose), 20 µg/kg/diet BPA (high dose), 4 µg/kg/diet diethylstilbesterol (DES), or a purified control diet. All pups were weaned onto a purified control diet. Indirect calorimetry was used to evaluate energy expenditure and substrate utilization in offspring at two and five months of age. At three months of age, a subset of animals was placed on a high fat diet for two months to evaluate the effect of perinatal BPA exposure on the susceptibility to diet-induced obesity. Perinatal exposure to the high BPA dose was associated with elevated body weight following exposure to a high-fat diet. Males exposed to the estrogenic DES also showed elevated body weight under a high-fat diet (p<0.01). Males in the high BPA condition showed impaired glucose tolerance (p<0.05 for area under the curve), while females in this treatment showed elevated blood glucose at the 60 and 120 minute timepoints in the test (p<0.05). Females in the high BPA condition eating a high-fat diet showed significantly increased visceral, subcutaneous (p<0.001), retroperitoneal (p<0.01) and brown adipose (p<0.05) fat pad weights. Males in the DES, low, and high BPA treatments eating high-fat chow all showed elevated retroperitoneal fat pad weights (p<0.01), while only males in the DES treatment showed elevated subcutaneous fat (p<0.05). Males exposed to the high dose of BPA but eating regular chow showed elevated brown adipose tissue (p<0.01) and retroperitoneal fat (p=0.059). These males also showed elevated energy expenditure (VO2) at two (p<0.01) and five months (p<0.001), but this difference was eliminated by exposure to a high fat diet. In all these studies provide evidence for increased susceptibility to diet induced obesity as a result of perinatal exposure to BPA.