Ahmed S, Atlas E
Environmental Health Science and Research Bureau, Health Canada, Ottawa, Ontario, Canada.
Int J Obes (Lond). 2016 Oct;40(10):1566-1573. doi: 10.1038/ijo.2016.95. Epub 2016 May 13.
BACKGROUND/OBJECTIVES: The use of bisphenol A (BPA) in consumer products and food packaging has been associated under certain conditions with a risk of negative health outcomes. This prompted its removal from many products and replacement with structural analogs. Bisphenol S (BPS) is one such analog, but its metabolic effects have not been fully characterized. The objective of our study was to determine whether BPS functions similarly to BPA at inducing adipogenesis.
Murine 3T3-L1 preadipocytes were used to evaluate and compare the adipogenic potential of BPS to BPA. Cells were treated with 0.01-50 μM BPS or 0.01-50 μM BPA and adipogenic effects were measured. Further, their ability to activate peroxisome proliferator-activated receptor gamma (PPARγ), an adipogenic transcription factor, was also determined.
Our results indicate that treatment of 3T3-L1 cells with BPS induced lipid accumulation and increased mRNA and protein expression of key adipogenic markers (1-50 μM; P<0.05). BPS treatment resulted in a higher expression of adipogenic markers as well as greater lipid accumulation when compared with BPA treatment. We showed that BPS can upregulate lipoprotein lipase, adipocyte protein 2, PPARγ, perilipin, adipsin and CCAAT/enhancer-binding protein alpha mRNA expression levels. Furthermore, using transcriptional assays, we showed that BPS and BPA can modestly activate PPARγ using a PPRE (PPARγ response element)-dependent luciferase construct by 1.5-fold (P<0.05). However, BPS but not BPA was able to competitively inhibit rosiglitazone (ROSI)-activated PPARγ, suggesting that BPS interacts with PPARγ distinctly from BPA. Co-treatment of cells with the selective PPARγ antagonist GW9662 inhibits BPS-, BPA-, ROSI- but not dexamethasone-dependent adipogenic differentiation.
Both BPA and BPS can enhance 3T3-L1 adipocyte differentiation in a dose-dependent manner and require PPARγ to induce adipogenesis. Through direct comparison, we show that BPS is a more potent adipogen than BPA.
背景/目的：在某些情况下，消费品和食品包装中使用双酚A（BPA）与负面健康结果风险相关。这促使其从许多产品中去除，并用结构类似物替代。双酚S（BPS）就是这样一种类似物，但其代谢效应尚未完全明确。我们研究的目的是确定BPS在诱导脂肪生成方面是否与BPA功能相似。
使用小鼠3T3-L1前脂肪细胞来评估和比较BPS与BPA的脂肪生成潜力。用0.01 - 50 μM BPS或0.01 - 50 μM BPA处理细胞，并测量脂肪生成效应。此外，还测定了它们激活过氧化物酶体增殖物激活受体γ（PPARγ，一种脂肪生成转录因子）的能力。
我们的结果表明，用BPS处理3T3-L1细胞会诱导脂质积累，并增加关键脂肪生成标志物的mRNA和蛋白质表达（0.01 - 50 μM；P<0.05）。与BPA处理相比，BPS处理导致脂肪生成标志物表达更高，脂质积累更多。我们发现BPS可上调脂蛋白脂肪酶、脂肪细胞蛋白2、PPARγ、围脂滴蛋白、脂肪酶和CCAAT/增强子结合蛋白α的mRNA表达水平。此外，通过转录分析，我们发现BPS和BPA使用依赖于PPRE（PPARγ反应元件）的荧光素酶构建体可适度激活PPARγ达1.5倍（P<0.05）。然而，BPS而非BPA能够竞争性抑制罗格列酮（ROSI）激活的PPARγ，这表明BPS与PPARγ的相互作用与BPA不同。用选择性PPARγ拮抗剂GW9662共同处理细胞可抑制BPS、BPA、ROSI诱导的，但不抑制地塞米松依赖的脂肪生成分化。
BPA和BPS均可剂量依赖性地增强3T3-L1脂肪细胞分化，且需要PPARγ来诱导脂肪生成。通过直接比较，我们表明BPS是比BPA更强效的脂肪生成剂。
