Perinatal exposure to bisphenol A at reference dose predisposes offspring to metabolic syndrome in adult rats on a high-fat diet.

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.