Mice exposed perinatally to the obesogenic endocrine disruptor bisphenol-A (BPA) show impaired central and behavioral leptin sensitivity in advance of diet-induced obesity: evidence for developmental programming of hypothalamic pro-opiomelanocortin (POMC) regulation

H. A. Mackay, Z. R. Patterson, A. Abizaid

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Bisphenol-A (BPA) is a component of polycarbonate plastic, and is commonly found in food and drink containers. BPA has been characterized as an endocrine disruptor capable of acting as a xenoestrogen in a variety of experimental models, and because it is capable of leaching out of food and drink containers, human exposure is nearly ubiquitous. Since BPA can cross the placenta and is also found in breast milk, adverse organizational effects due to early-life exposure are of particular concern. Recent evidence from our lab has demonstrated in mice that early-life exposure to environmentally relevant doses of BPA yields a phenotype characterized by a predisposition to adult obesity in female mice and metabolic disturbance in males. Given the sensitivity of the developing hypothalamus to the organizational effects of sex steroids, we hypothesized that early-life BPA exposure adversely affects the development of hypothalamic feeding circuitry in order to bring about this phenotype. To test this hypothesis, we used male and female CD-1 mice exposed pre- and post-natally to either a control diet, a diet containing BPA (appx. 13.5 µg/kg/day), or the estrogenic diethylstilbestrol (DES) as a positive control (appx. 3 µg/kg/day). Serum from pups was collected on PND2, 8, 10, 12, 16, and 21 for analysis of circulating leptin. Results from this study show that BPA and DES exposed pups have respectively delayed and blunted postnatal leptin surges – a state of affairs that points to a role for leptin in the organizational effects of early-life xenoestrogen exposure. Adult offspring from this experiment were resistant to leptin-induced suppression of food intake, body weight loss, and hypothalamic POMC upregulation. Taken together, these data suggest that BPA, a known obesogen, may exert its effects through developmental programming of the hypothalamic melanocortin circuitry.