Bisphenol A-induced metabolic disorders: From exposure to mechanism of action

Bisphenol A (BPA) is considered as ubiquitous xenooestrogen and an endocrine disrupting chemical which has deleterious effects on endocrine functions. Human populations are continuously exposed to BPA as it is abundant in daily life. It has been found to be associated with wide range of metabolic disorders notably type 2 diabetes mellitus (DM). Numerous epidemiological studies have been conducted to find its role in development of DM. Experimental studies have found that BPA exposure is associated with pathogenesis of DM and also considered as a risk factor for gestational diabetes. Being a lipophilic compound, BPA is preferably accumulated in adipose tissues where it alters the production of adipokines that play important roles in insulin resistance. BPA induces apoptosis by caspase activation after mitochondrial damage and it impairs insulin signaling pathways by altering associated ion channel activity especially potassium channels. Perinatal exposure of BPA makes offspring more susceptible to develop DM in early years. Epigenetic modifications are the key mechanisms for BPA-induced metabolic re-programming, where BPA alters the expression of DNA methyltransferases involved in methylation of various genes. In this way, DNA methyltransferase controls the expression of numerous genes including genes important for insulin secretion and signaling. Furthermore, BPA induces histone modifications and alters miRNA expression. In this article, we have briefly described the sources of BPA exposure to human being and summarized the evidence from epidemiological studies linking DM with BPA exposure. Additionally, we have also highlighted the potential molecular pathways for BPA-induced DM.