Maia Maria Luz, Sousa Sara, Pestana Diogo, Faria Ana, Teixeira Diana, Delerue-Matos Cristina, Domingues Valentina Fernandes, Calhau Conceição
REQUIMTE/LAQV-GRAQ, Instituto Superior de Engenharia do Porto, Instituto Politécnico do Porto, 4200-072, Porto, Portugal; Center for Research in Health Technologies and Information Systems, 4200-450, Porto, Portugal.
Center for Research in Health Technologies and Information Systems, 4200-450, Porto, Portugal; Nutrição e Metabolismo, NOVA Medical School Faculdade de Ciências Médicas Universidade Nova de Lisboa, 1169-056, Lisboa, Portugal.
Environ Pollut. 2022 Feb 1;294:118639. doi: 10.1016/j.envpol.2021.118639. Epub 2021 Dec 4.
Brominated flame retardants (BFRs) are chemicals employed to lower the flammability of several objects. These endocrine disruptor chemicals are lipophilic and persistent in the environment. Due to these characteristics some have been restricted or banned by the European Union, and replaced by several new chemicals, the novel BFRs (NBFRs). BFRs are widely detected in human samples, such as adipose tissue and some were linked with altered thyroid hormone levels, liver toxicity, diabetes and metabolic syndrome in humans. However, the disturbance in lipid metabolism caused by BFRs with emphases to NBFRs remains poorly understood. In this study, we used a pre-adipocyte (3T3-L1) cell line and a hepatocyte (HepG2) cell line to investigate the possible lipid metabolism disruption caused by four BFRs: hexabromobenzene (HBB), pentabromotoluene (PBT), 2-ethylhexyl-2,3,4,5-tetrabromobenzoate (TBB) and hexabromocyclododecane (HBCD). For that purpose, proliferation and Oil Red O assays, as well as, medium fatty acids profile evaluation using Gas chromatography and RNA extraction for quantitative RT-PCR assays were performed. We detected a significant reduction in the proliferation of preadipocytes and an increased lipid accumulation during differentiation caused by HBB. This BFR also lead to a significant increased expression of IL-1β and decreased expression of PGC-1α and adiponectin. Nevertheless, PBT, TBB and HBCD show to increase lipid accumulation in hepatocytes. PBT also display a significant increase of PPARγ gene expression. Lipid accumulation in the cells can occur by diverse mechanisms depending on the BFR. These results highlight the importance of endocrine disruptor compounds in obesity etiopathogeny.
溴化阻燃剂（BFRs）是用于降低多种物品可燃性的化学物质。这些内分泌干扰化学物质具有亲脂性且在环境中持久存在。由于这些特性，其中一些已被欧盟限制或禁止，并被几种新的化学物质所取代，即新型溴化阻燃剂（NBFRs）。BFRs在人体样本中广泛被检测到，如脂肪组织，并且一些与人体甲状腺激素水平改变、肝脏毒性、糖尿病和代谢综合征有关。然而，BFRs，尤其是NBFRs对脂质代谢的干扰仍知之甚少。在本研究中，我们使用前脂肪细胞（3T3-L1）细胞系和肝细胞（HepG2）细胞系来研究四种BFRs：六溴苯（HBB）、五溴甲苯（PBT）、2-乙基己基-2,3,4,5-四溴苯甲酸酯（TBB）和六溴环十二烷（HBCD）可能引起的脂质代谢紊乱。为此，进行了增殖和油红O测定，以及使用气相色谱评估培养基脂肪酸谱和用于定量RT-PCR测定的RNA提取。我们检测到HBB导致前脂肪细胞增殖显著降低以及分化过程中脂质积累增加。这种BFR还导致IL-1β表达显著增加以及PGC-1α和脂联素表达降低。然而，PBT、TBB和HBCD显示会增加肝细胞中的脂质积累。PBT还显示PPARγ基因表达显著增加。细胞中的脂质积累可通过多种机制发生，这取决于BFR。这些结果突出了内分泌干扰化合物在肥胖病因学中的重要性。
