Bisphenol A (BPA) has a variety of adverse effects on human health; therefore, BPA analogs are increasingly used as replacements. Notably, recent studies have revealed that BPA exposure induced hepatic lipid accumulation, but few studies are available regarding the similar effects of other bisphenol analogues (BPs). Thus, in the present study, a high-content screening (HCS) assay was performed to simultaneously evaluate the hepatic lipid accumulation of 13 BPs in vitro. The BPs induced lipid deposition in HepG2 cells ranking as below: 4,4′-thiodiphenol (TDP) < bisphenol S (BPS) < 4,4′-dihydroxybenzophenone (DHBP) < tetrabromobisphenol A (TBBPA) < tetrachlorobisphenol A (TCBPA) < bisphenol E (BPE) < bisphenol F (BPF) < bisphenol B (BPB) < bisphenol AF (BPAF) < bisphenol A (BPA) < bisphenol C (BPC) < tetramethylbisphenol A (TMBPA) < bisphenol AP (BPAP). Meanwhile, Oil Red O staining and triacylglycerol detection further validated the lipid accumulation elicited by the latter 8 BPs, which exhibited the more significant effects on lipid deposition. Mechanistically, significantly increased expressions of genes involved in fatty acid synthesis and nuclear receptors and decreased levels of genes associated with fatty acid β-oxidation were observed under BPs treatment. Therefore, the present work is the first to systematically provide direct evidence for BPs-induced hepatic lipid accumulation in vitro via HCS, which can be helpful for safety assessments of BPs.

双酚A（BPA）对人体健康有多种不良影响；因此，BPA类似物越来越多地用作替代品。值得注意的是，最近的研究表明，BPA暴露会引起肝脂质蓄积，但是关于其他双酚类似物（BPs）的类似作用的研究很少。因此，在本研究中，进行了高含量筛选（HCS）测定以同时评估的13个BP肝脂质积聚在体外。BP诱导的HepG2细胞脂质沉积排名如下：4,4'-硫代双酚（TDP）<双酚S（BPS）<4,4'-二羟基二苯甲酮（DHBP）<四溴双酚A（TBBPA）<四氯双酚A（TCBPA）<双酚E（BPE）<双酚F（BPF）<双酚B（BPB）<双酚AF（BPAF）<双酚A（BPA）<双酚C（BPC）<四甲基双酚A（TMBPA）<双酚AP（BPAP）。同时，油红O染色和三酰基甘油检测进一步验证了后8个BP引起的脂质蓄积，这对脂质沉积具有更显着的影响。从机制上讲，在BPs处理下，观察到与脂肪酸合成和核受体有关的基因表达显着增加，而与脂肪酸β-氧化有关的基因水平下降。因此，通过HCS在体外进行，这有助于评估BP的安全性。