Targeted Metabolomics and Widely Targeted Quantitative Lipidomics Reveal Synergistic Metabolic Interference in Adipose Tissue After the Combined Chronic Exposure to Bisphenol A Substitutes, Bisphenol S and Bisphenol F, and Fructose in Male Rats

The combined effect of environmental exposure and dietary behavior plays a vital role in the occurrence of diseases. Bisphenol S (BPS) and bisphenol F (BPF) are the most commonly used substitutes for bisphenol A (BPA). Previous studies have shown that the combined exposure to BPA and fructose caused significant disturbances in glycolipid metabolism in adipose tissue, however, the interference caused by the combined exposure to BPS and fructose or BPF and fructose on adipose tissue is still unclear. In the present study, we performed a integrated analysis of targeted energy metabolomics and widely targeted quantitative lipidomics on the adipose tissue of Sprague Dawley rats after combined exposure to 2 levels of BPS or BPF (lower dose: 0.25, and higher dose: 25 μg/kg every other day) and 5% fructose for 6 months. Based on the results, lower dose BPS combined with fructose increased succinate significantly, while higher dose BPS or lower dose BPF combined with fructose decreased succinate significantly. Additionally, lower dose BPS combined with fructose might lead to polyunsaturated lipid depletion, while higher dose BPS combined with fructose exposure might lead to choline and carnitine depletion; lower dose BPF combined with fructose might inhibit lipolysis, while higher dose BPF combined with fructose might cause accumulation of free fatty acids. These results indicated the response patterns of adipose tissue to different dose of BPS or BPF combined with fructose were significantly different, and the adipocyte succinate signaling pathway might be the important target for metabolic remodeling in adipose tissue.