# Co-Exposure to Bisphenol A and a High-Fat Diet Induces Insulin Resistance via Suppression of Insulin Signaling Molecule Expression and GLUT4 Translocation

## TL;DR

This study shows that combining bisphenol A exposure with a high-fat diet worsens insulin resistance by disrupting insulin signaling and GLUT4 translocation in muscle cells.

## Contribution

The study reveals novel mechanisms by which co-exposure to BPA and a high-fat diet impairs insulin signaling and GLUT4 translocation.

## Key findings

- Co-exposure to BPA and a high-fat diet reduces insulin signaling molecule expression in mouse muscle.
- BPA and palmitic acid inhibit GLUT4 translocation in C2C12 myotubes, contributing to insulin resistance.
- Combined exposure significantly alters insulin signaling pathways in both in vivo and in vitro models.

## Abstract

While the adverse health effects of bisphenol A (BPA) or high-fat diet (HFD) exposure alone have been relatively well documented, the mechanisms underlying their combined impact on insulin resistance and type 2 diabetes remain poorly understood. In this study, we observed the effects of 90 days of treatment with BPA and an HFD on insulin resistance in mouse gastrocnemius muscle, as well as the expression of signaling molecules and proteins potentially associated with glucose transporter type 4 (GLUT4) translocation. Additionally, C2C12 myotubes were co-treated with BPA and palmitic acid (PA) to observe the effects on insulin signaling molecules, GLUT4 translocation, and insulin resistance. Specifically, in vitro cellular experiments further demonstrated that BPA and PA inhibited GLUT4 translocation from the nucleus to the cell membrane. Taken together, co-exposure to BPA and an HFD (or PA) treatment significantly altered the expression of insulin signaling molecules in both gastrocnemius muscle and C2C12 cells, suggesting a potential link to their impacts on insulin resistance and GLUT4 translocation.