Long-term exposure to low doses of bisphenol S has hypoglycaemic effect in adult male mice by promoting insulin sensitivity and repressing gluconeogenesis

Highlights: • Environmentally relevant concentration of BPS exposure leads to hypoglycaemia. • BPS increases insulin sensitivity in different nutritionally conditioned mice. • Low dose BPS reduces gluconeogenesis in high-fat diet-fed mice. • BPS exposure disrupts thyroid hormone signalling. Bisphenol S (BPS), an industrial chemical that is a structural analogue of bisphenol A, has been widely reported to be involved in various biological processes. Epidemiological studies have demonstrated that exposure to BPS is associated with dysglycaemia-related health outcomes. The role of BPS in glucose metabolism, however, remains controversial. In this study, we aimed to investigate the effects of chronic exposure to environmentally relevant concentrations of BPS on glucose metabolism in different nutritionally conditioned mice. Our results revealed that 1-month exposure to a BPS dosage of 100 μg/kg bw slightly increased the insulin sensitivity of normal diet-fed mice, and that this effect was enhanced after 3-month exposure. It was also found that BPS exposure attenuated insulin resistance and reduced gluconeogenesis in high-fat diet-fed mice. Consequently, the concentrations of hepatic metabolites related to glucose metabolism were altered in both groups of mice. Moreover, thyroid hormone signalling was disrupted after BPS administration in both groups of mice. Taken together, our results demonstrated that chronic exposure to environmentally relevant concentrations of BPS exerted an unexpected hypoglycaemic effect in mice of different nutritional statuses, and that this was partly attributable to disrupted thyroid hormone signalling.