Bisphenol A (BPA), a widely used environmental endocrine disruptor, has been reported to disrupt glucose homeostasis. BPA exposure may be a risk factor for type 2 diabetes. In this study, we investigated the effects of early-life BPA exposure on metabolic syndrome in rat offspring fed a normal diet and a high-fat diet. Pregnant Wistar rats were exposed to BPA (50, 250, or 1250 μg/kg · d) or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a normal diet or a high-fat diet after weaning. Body weight, parameters of glucose and lipid metabolism, morphology, and function of β-cells were measured in offspring. On a normal diet, perinatal exposure to 50 μg/kg · d BPA resulted in increased body weight, elevated serum insulin, and impaired glucose tolerance in adult offspring. On a high-fat diet, such detrimental effects were accelerated and exacerbated. Furthermore, severe metabolic syndrome, including obesity, dyslipidemia, hyperleptindemia, hyperglycemia, hyperinsulinemia, and glucose intolerance, was observed in high-fat-fed offspring perinatally exposed to 50 μg/kg · d BPA. No adverse effect of perinatal BPA exposure at 250 and 1250 μg/kg · d was observed no matter on a normal diet or a high-fat diet. These results suggest that perinatal exposure to BPA at reference dose, but not at high dose, impairs glucose tolerance in adult rat offspring on a normal diet and predisposes offspring to metabolic syndrome at adult on a high-fat diet. High-fat diet intake is a trigger that initiates adverse metabolic effects of BPA.

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Bisphenol A (BPA) is one of the environmental endocrine disrupting chemicals, which is present ubiquitously in daily life. Accumulating evidence indicates that exposure to BPA contributes to metabolic syndrome. In this study, we examined whether perinatal exposure to BPA predisposed offspring to fatty liver disease: the hepatic manifestation of metabolic syndrome. Wistar rats were exposed to 50 mg/kg per day BPA or corn oil throughout gestation and lactation by oral gavage. Offspring were fed a standard chow diet (SD) or a high-fat diet (HFD) after weaning. Effects of BPA were assessed by examination of hepatic morphology, biochemical analysis, and the hepatic expression of genes and/or proteins involved in lipogenesis, fatty acid oxidation, gluconeogenesis, insulin signaling, inflammation, and fibrosis. On a SD, the offspring of rats exposed to BPA exhibited moderate hepatic steatosis and altered expression of insulin signaling elements in the liver, but with normal liver function. On a HFD, the offspring of rats exposed to BPA showed a nonalcoholic steatohepatitis-like phenotype, characterized by extensive accumulation of lipids, large lipid droplets, profound ballooning degeneration, impaired liver function, increased inflammation, and even mild fibrosis in the liver. Perinatal exposure to BPA worsened the hepatic damage caused by the HFD in the rat offspring. The additive effects of BPA correlated with higher levels of hepatic oxidative stress. Collectively, exposure to BPA may be a new risk factor for the development of fatty liver disease and further studies should assess whether this finding is also relevant to the human population.

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