UPLC-QqQMS based targeted metabolomics reveal combination impact on metabolism caused by bisphenol AF and fructose combined exposure in male mice

Bisphenol AF (BPAF), a fluorinated alternative to the plasticizer bisphenol A (BPA), is found in both the environment and the human body. Fructose is one of the sweeteners that has been widely used in recent years. Prior research has verified that the combined exposure to fructose and BPA considerably worsened the impact on glycolipid metabolism. However, it is currently unclear whether BPAF have a combination effect on health with fructose. Serum glucose and insulin, liver biochemistry, histology of the liver and adipose tissue, serum profiles of amino acids, vitamins, bile acids, steroid hormones, catecholamines, and adipocytokines like leptin, omentin-1, adiponectin, asprosin, and adipocyte fatty acid binding protein (A-FABP) of male mice were all investigated in this study following a week of combined exposure to two doses of BPAF (lower dose: 0.25, and higher dose: 25 μg/kg daily). The results showed that simultaneous exposure to lower doses of BPAF and fructose considerably increased blood insulin and liver coefficient, total bilirubin, direct bilirubin, and glucose while significantly decreasing body weight, food intake, liver creatinine, and serum leptin, asprosin, and A-FABP. According to histology analysis, adipocyte enlargement may result from lower dose BPAF and fructose combined exposure, while bile duct dilatation may result from both lower and higher doses of BPAF combined with fructose. Concurrently, the combination of lower doses of BPAF and fructose increased the release of adrenocortical hormones and catecholamines, worsened metabolic disorders in amino acids such as histidine, arginine and proline, branched chain amino acid (isoleucine), and aromatic amino acids (tryptophan and phenylalanine), and aggravated the depletion of vitamin B12 and A. Interestingly, following the combined exposure to BPAF and fructose, bile acids including taurocholic acid, deoxycholic acid, cholic acid, and taurine ursodeoxycholic acid rose in a dose-dependent manner. According to these results, exposure to fructose and BPAF together may have a more detrimental effect on metabolism than either substance alone. Further research should be conducted to verify the impact of joint exposure to BPAF and fructose on human.