Multi-omics analysis reveals BPF exposure causes hepatic glucose and lipid metabolism disorder in rats by disrupting energy homeostasis

Bisphenol F (BPF) is one of the main substitutes for Bisphenol A (BPA) and is widely used in the manufacture of household products. In addition, BPF threatens human health through environmental pollution and the food chain. However, the hepatotoxicity of BPF and its effects on glucose and lipid metabolism remain unclear. This study used male SD rats as an animal model to investigate the hepatotoxicity of BPF and its effects on glucose and lipid metabolism. The results of the HE staining, serum and liver biochemical indicators show that BPF can damage the basic structure of the liver, cause liver dysfunction and lead to disorders of liver glucose metabolism and lipid metabolism. Furthermore, we conducted metabolomics and proteomics analyses on the livers of the BPF exposed group at 100 mg/kg/d in comparison with the control group. The results indicated that BPF exposure had a significant effect on liver metabolism. Combined with biological analysis and the validation of changes in genes and proteins related to glucose and lipid metabolism in the liver, it was elucidated that BPF can promote fatty acid oxidation and inhibit fatty acid synthesis through the AMPK and PPAR signaling pathways, leading to a reduction in fatty acids. Furthermore, it has been demonstrated that BPF can promote glycogen synthesis and gluconeogenesis via the AKT pathway, which can result in disorders of glucose metabolism.