Bisphenol A Coupled with a High-Fat Diet Promotes Hepatosteatosis through Reactive-Oxygen-Species-Induced CD36 Overexpression

Abstract

Bisphenol A (BPA) is an endocrine-disrupting chemical that affects lipid metabolism and contributes to non-alcoholic fatty liver disease (NAFLD). The mechanism of BPA exposure in hepatic lipid accumulation and its potential effect on NAFLD remain unclear. This study investigated the effect of BPA-exposure-induced hepatic lipid deposition on the pathology of NAFLD and its underlying mechanism in vitro and in vivo. BPA increased intracellular reactive oxygen species (ROS) levels, and promoted fatty acid uptake through upregulation of a free fatty acid uptake transporter, cluster of differentiation 36 (CD36), in HUH-7 cells. Additionally, C57BL/6 mice administered a high-fat/high-cholesterol/high-cholic acid diet (HFCCD) and BPA (50 mg/kg body weight) for 8 weeks developed a steatohepatitis-like phenotype, characterized by alpha-smooth muscle actin (α-SMA, an indicator of hepatic fibrosis) and cleaved caspase 3 (an indicator of apoptosis) in hepatic tissue; moreover, they had a higher oxidative stress index of 8-hydroxydeoxyguanosine (8-OHdG) in liver tissue compared to the control group. Treatment with ROS scavenger n-acetylcysteine (NAC) ameliorated BPA-mediated HFCCD-induced lipid accumulation and steatohepatitis in the livers of treated mice. Our study indicates that BPA acts synergistically to increase hepatic lipid uptake and promote NAFLD development by stimulating ROS-induced CD36 overexpression.

Protective effects of Allium macrostemon extract on adipose tissue and liver dysregulation induced by high-fat diet and bisphenol A in C57BL/6 mice

“…1). In accordance with our data, an increase in serum TG levels by combined exposure to HF and BPA has been reported earlier, and previous studies have reported BPA-ampli ed promotion of fatty liver by enhancing reactive oxygen species production and hepatic lipid accumulation (Lee et al 2022, Pirozzi et al 2020). Activation of ER stress is a key pathological mechanism of steatosis (Zhang et al 2014).…”

“…These results indicated that BPA may exert toxicity by inhibiting body weight gain. This result agrees with the results of a previous study in which 8-week-old HF/ high-cholesterol/high-cholic acid diet (HFCCD)-fed C57BL/6 male mice were treated with 50 mg/kg/day BPA for 8 weeks (Lee et al 2022). BPA coupled with HFCCD promoted the development of fatty liver by enhancing reactive oxygen species production in hepatocytes.…”

Application of In Vitro Models for Studying the Mechanisms Underlying the Obesogenic Action of Endocrine-Disrupting Chemicals (EDCs) as Food Contaminants—A Review

“…Wada et al [ 205 ] showed that BPA and 4-NP exposure stimulated lipid accumulation in Huh-7 cells. Similarly, Lee et al [ 206 ] confirmed that BPA increased intracellular lipid accumulation and fatty acid uptake in Huh-7 cells.…”

CD36-Fatty Acid-Mediated Metastasis via the Bidirectional Interactions of Cancer Cells and Macrophages

“…Another study further explored that at very low doses of BPA can induces prostate cancer cells migration [ 91 ], and similar effects were observed in breast cancer cells [ 92 , 93 ]. However, the link between BPA and CD36 expression has been determined in non-alcoholic fatty liver disease (NAFLD), which BPA increases hepatic lipid uptake by stimulating ROS-induced CD36 overexpression [ 94 ]. Based on this evidence, further studies must be investigated to understand the underlying mechanism and association of BPA with CD36 in cancer progression and immune response.…”