Bisphenol S exposure induces cardiac remodeling and aggravates high-fat diet-induced cardiac hypertrophy in mice

Abstract

Bisphenol S (BPS) is widely used in the manufacture products and increase the risk of cardiovascular diseases. The effect of the association between obesity and BPS on cardiac outcomes is still unknown. Male C57BL/6 mice were divided into standard chow diet (SC; 15 kJ/g), standard chow diet + BPS (SCB), high-fat diet (HF; 21 kJ/g), and high-fat diet + BPS (HFB). Over 12 weeks, the groups were exposed to BPS through drinking water (dose: 25 μg/kg/day) and/or a HF diet. We evaluated: body mass (BM), total cholesterol, systolic blood pressure (SBP), left ventricle (LV) mass, and cardiac remodeling. In the SCB group, BM, total cholesterol, and SBP increase were augmented in relation to the SC group. In the HF and HFB groups, these parameters were higher than in the SC and SCB groups. Cardiac hypertrophy was evidenced by augmented LV mass and wall thickness, and ANP protein expression in all groups in comparison to the SC group. Only the HFB group had a thicker LV wall than SCB and HF groups, and increased cardiomyocyte area when compared with SC and SCB groups. Concerning cardiac fibrosis, SCB, HF, and HFB groups presented higher interstitial collagen area, TGFβ, and α-SMA protein expression than the SC group. Perivascular collagen area was increased only in the HF and HFB groups than SC group. Higher IL-6, TNFα, and CD11c protein expression in all groups than the SC group evidenced inflammation. All groups had elevated CD36 and PPARα protein expression in relation to the SC group, but only HF and HFB groups promoted cardiac steatosis with increased perilipin 5 protein expression than the SC group. BPS exposure alone promoted cardiac remodeling with pathological concentric hypertrophy, fibrosis, and inflammation. Diet-induced remodeling is aggravated when associated with BPS, with marked hypertrophy, alongside fibrosis, inflammation, and lipid accumulation.

Keywords: Bisphenol S; Heart; Morphology; Obesity.