Investigation of the Effects of Bisphenol A and High-Fat Diet Co-Exposure on the Suppression of Insulin Signaling Molecule Expression and GLUT4 Translocation Leading to Insulin Resistance

Background/Objectives: Bisphenol A (BPA) is a pervasive environmental endocrine disruptor, and the lifestyle associated with a high-fat diet is becoming increasingly common. The precise relationship between these factors and the high incidence of insulin resistance and type 2 diabetes worldwide in recent years remains unclear. Given the critical role of skeletal muscle in maintaining systemic glucose metabolism, this study aimed to explore the potential effects of co-exposure to BPA and a high-fat diet on insulin signaling molecules and GLUT4 translocation in mouse gastrocnemius muscle and C2C12 myotubes through both in vivo and in vitro experiments. Methods: We observed the effects of 90 days of BPA and high-fat diet treatment on animal insulin resistance, as well as the expression levels of potential signaling molecules and proteins related to GLUT4 translocation. In vitro experiments involved co-treatment of C2C12 myotubes with BPA and palmitic acid to observe their effects on insulin signaling molecules, GLUT4 translocation, and insulin resistance. Results: Animals co-exposed to BPA and a high-fat diet exhibited a significant increase in insulin resistance indices and impaired oral glucose tolerance. During this process, the expression levels of insulin signaling molecules were markedly reduced, and GLUT4 translocation was significantly blunted. In vitro cellular experiments further demonstrated that BPA and palmitic acid could inhibit the expression levels of GLUT4 on the cell membrane, i.e., the translocation of GLUT4 from the nucleus to the cell membrane was significantly suppressed. Conclusions: Co-exposure to BPA and a high-fat diet significantly affected the expression levels of insulin signaling molecules in gastrocnemius tissue and C2C12 cells, which may be closely related to their effects on inducing insulin resistance and affecting GLUT4 translocation.