VEGF-A Remissions Brown Adipocyte Function Following Combined Exposure to Bisphenol A and a High-Fat Diet

Obesity has emerged as a global health crisis, with its pathogenesis being closely linked to metabolic dysregulation in brown adipose tissue (BAT). However, the underlying mechanisms by which high-fat diets and environmental endocrine disruptors, such as bisphenol A (BPA), affect BAT remain largely unknown. This study was conducted to investigate how combined exposure to BPA and a high-fat diet influences BAT function and the development of obesity via the VEGF/VEGFR2/PI3K/AKT pathway.Male C57BL/6J mice were randomly assigned to four groups and received different treatments for 90 days: a normal chow diet (NCD), a normal chow diet supplemented with BPA (NCD + BPA), a high-fat diet (HFD), or a high-fat diet supplemented with BPA (HFD + BPA). Additionally, cell experiments were carried out using C3H10T1/2 cells induced to differentiate into brown adipocytes. These cells were exposed to different combinations of BPA and palmitic acid (PA).To comprehensively assess the effects on mice and cells, a variety of assays were employed, including cell viability assays, hematoxylin and eosin (H&E) staining, enzyme-linked immunosorbent assay (ELISA), immunohistochemistry, immunofluorescence, Western blotting, and mitochondrial electron microscopy.The combined treatment of BPA and HFD (PA) successfully established an animal obesity model and a cellular triglyceride (TG) accumulation model. BPA and HFD exposure affected serum lipid levels and the expression of inflammatory factors in animals. It also inhibited brown adipose tissue thermogenesis and the expression of VEGF pathway proteins, leading to a reduction in capillaries and mitochondrial damage. Similarly, the combined treatment of BPA and PA influenced the expression of inflammatory factors in mature brown adipose cells and inhibited the expression of related proteins.Overall, combined exposure to BPA and a high-fat diet impairs BAT function through multiple mechanisms, including inflammation, thermogenic dysfunction, microvascular damage, mitochondrial injury, and alteration of the VEGF/VEGFR2/PI3K/AKT pathway. These findings suggest that such combined exposure ultimately promotes the development of obesity.