DISTAV, Dipartimento di Scienze della Terra, dell'Ambiente e della Vita, Università di Genova, Genova, Italy.
Chemosphere. 2013 May;91(8):1123-9. doi: 10.1016/j.chemosphere.2013.01.016. Epub 2013 Feb 9.
Bisphenol A (BPA), used in the manufacture of polycarbonate plastic and epoxy resin, is one of the most abundant endocrine disruptors in the environment, considered as a xenoestrogen. BPA has recently become of additional public health concern because of increasing evidence of deleterious effects on metabolism. Dietary intake seems the most important route for BPA exposure, followed by rapid biotransformation in the gut and liver and elimination in the urine. Although hepatocytes can represent a significant target for this compound, little is known on the direct effects and mechanisms of action of BPA on lipid homeostasis at the cellular level. In this work, the effects of BPA (0.3-3-30-300 ng mL(-1), 24 h) were investigated in rat FaO hepatoma, a well differentiated liver cell line. At both 30 and 300 ng mL(-1), BPA significantly increased intracellular triglyceride (TAG) content and lipid accumulation in lipid droplets (LDs), without affecting cell viability. The effects of BPA were associated with decreased mRNA levels of the transcription factors Peroxisome Proliferator-Activated Receptor (PPAR) isoforms α and βδ, as well as of their downstream genes acyl-CoA oxidase (AOX) and carnitine palmitoyl transferase (CPT1) involved in lipid oxidation. No increase in transcription of lipogenic genes was observed. BPA also decreased mRNA levels of ApolipoproteinB (apoB) and the extracellular TAG content, indicating alterations in lipid secretion. FaO cells did not express Estrogen Receptor α (ERα and showed a very low expression of ERβ compared to rat liver. All the effects of BPA were prevented by cell pretreatment with Wortmannin, indicating the involvement of phosphatidyl inositol-3 kinase activation. The results demonstrate a direct action of BPA on lipid homeostasis in FaO cells through interference with lipid oxidation and secretion, and add further information on the cellular pathways that can be perturbed by this compound.
双酚 A（BPA），用于制造聚碳酸酯塑料和环氧树脂，是环境中最丰富的内分泌干扰物之一，被认为是一种外源性雌激素。由于越来越多的证据表明其对新陈代谢有有害影响，BPA 最近引起了公众对健康的额外关注。膳食摄入似乎是 BPA 暴露的最重要途径，其次是在肠道和肝脏中的快速生物转化以及在尿液中的消除。尽管肝细胞可能是该化合物的重要靶标，但对于 BPA 对细胞水平脂质稳态的直接影响和作用机制知之甚少。在这项工作中，研究了 BPA（0.3-3-30-300ngmL(-1)，24 小时）对大鼠 FaO 肝癌细胞的影响，FaO 肝癌细胞是一种分化良好的肝细胞系。在 30 和 300ngmL(-1)时，BPA 显著增加了细胞内甘油三酯（TAG）含量和脂质在脂滴（LDs）中的积累，而不影响细胞活力。BPA 的作用与转录因子过氧化物酶体增殖物激活受体（PPAR）同工型α和βδ以及它们下游基因酰基辅酶 A 氧化酶（AOX）和肉碱棕榈酰转移酶（CPT1）的 mRNA 水平降低有关，这些基因参与脂质氧化。未观察到脂肪生成基因转录增加。BPA 还降低了载脂蛋白 B（apoB）的 mRNA 水平和细胞外 TAG 含量，表明脂质分泌发生改变。FaO 细胞不表达雌激素受体 α（ERα），与大鼠肝脏相比，ERβ 的表达水平非常低。Wortmannin 预处理细胞可防止 BPA 的所有作用，表明涉及磷脂酰肌醇-3 激酶的激活。研究结果表明，BPA 通过干扰脂质氧化和分泌直接作用于 FaO 细胞的脂质稳态，并提供了有关该化合物可干扰的细胞途径的更多信息。
