Endoplasmic reticulum stress is associated with cardiac effects of bisphenol S independently of a high-fat diet

Obesity and endocrine disruptors (EDs) promote endoplasmic reticulum (ER) stress, a mechanism associated with cardiovascular diseases. Among EDs, BPS is widely used in consumer products. Whether BPS promotes cardiac ER stress, either alone or combined with a high-fat diet, remains unclear. Male C57BL/6 mice were assigned to a standard chow diet (SC-15 kJ/g), SC+BPS (SCB), high-fat diet (HF-21 kJ/g), or HF+BPS (HFB), receiving BPS (25 μg/kg/day) through their drinking water for 12 weeks. Body mass (BM), lipid profile, cardiac risk ratio, heart mass, and cardiac ER stress, apoptosis, and oxidative stress markers were assessed. A high-fat diet intake increased BM gain, total cholesterol, cardiac risk ratio, and heart mass compared with standard chow diet intake. These parameters were higher in the SCB group than in the SC group. ER stress (GRP78, ATF4, and CHOP protein expression), pro-apoptotic (BAX protein expression and caspase 3 immunostaining), and pro-oxidative (NOX2 and NOX4 protein expression as well as MDA levels) markers were elevated in high-fat diet-fed animals compared with standard chow-fed animals. BPS exposure increased these parameters in standard chow-fed animals. High-fat diet intake reduced BCL2 expression and increased the BAX/BCL2 ratio compared with standard chow diet intake. BPS exposure increased BCL2 expression in standard chow-fed animals and increased the BAX/BCL2 ratio in high-fat diet-fed animals. ER stress appears to play a role in the cardiac effects of BPS. BPS exposure exacerbated the high-fat diet-induced pro-apoptotic response.