In vivo bisphenol-A exposure in combination with high-fat diet modulates murine innate immune responses (INC6P.345)

Abstract

Abstract The recent obesity epidemic has led to an expansion in our understanding of the link between adipose tissue and inflammation. The prevalent use of bisphenol-A (BPA) in food containers and other products provides an additional environmental challenge to the immune system. BPA disrupts the action of physiologic estrogens by binding to estrogen receptors and has previously been shown to impact immune responses. We explored the combined effects of high-fat diet and in vivo BPA exposure on spleen innate immune mediators. BPA treatment (2.5 or 25.0 ug/kg body weight per day; 4 weeks) reduced the LPS-induced secretion of KC chemokine, a neutrophil chemotaxin, by 25% and 40% respectively in normal diet mice, with a more dramatic BPA-induced decrease in KC secretion observed in high-fat fed mice. High-fat diet increased TNF-α mRNA expression overall compared to normal diet, and high dose-BPA reduced LPS-stimulated TNF-α mRNA expression in both normal (19%) and high-fat fed (34%) mice. High-fat fed mice also had a greater increase in LPS-induced COX-2 mRNA expression than normal diet mice, with BPA modulating expression in both groups in a dose dependent manner. High-fat diet and low dose BPA exposure increased non-fasting blood glucose levels by 30% on average when compared to control normal diet mice. These data demonstrate that peripubertal BPA exposure dampens aspects of innate immune function and that BPA combined with high-fat diet may disrupt glucose metabolism.