Abstract：Objective To investigate the effects of 2, 2', 4, 4'-tetrabromodiphenyl ether ( BDE-47 ) on the differentiation of mouse embryonic fibroblasts-3T3-L1, so as to provide the basis for revealing the mechanism of environmental obesity factors. Methods The 3T3-L1 cells were divided into five BDE-47 intervention groups ( 25, 18.75, 12.5, 7.5 and 2.5 µmol/L ), a positive control group (1 µmol/L 2, 4-thiazolidinedione) and a negative control group ( 0.1% dimethyl sulfoxide ) for the induction of differentiation. The lipid droplet accumulation in adipocytes was observed by oil red O staining treatment and detection of optical desity ( OD ) on the eighth day of differentiation. Triglyceride ( TG ) content was measured using the histiocyte TG enzymatic assay kit. The mRNA expression of adiponectin and peroxisome proliferator activated receptor-γ ( PPARγ ) was measured by RT-PCR. Results The positive areas of oil red O staining, OD values, TG content and mRNA expression of adiponectin and PPARγ in 3T3-L1 cells were significantly different among seven groups ( P<0.05 ). The positive areas of oil red O staining and OD values in the BDE-47 groups with different concentrations were higher than those in the negative control group ( P<0.05 ). The 18.75 µmol/L BDE-47 group had higher TG levels than the negative control group ( P<0.05 ). The mRNA expression of PPARγ in the 25, 18.75, 12.5, and 7.5 µmol/L BDE-47 groups and the positive control group was higher than that in the negative control group ( P<0.05 ). The mRNA expression of PPARγ in the 12.5 µmol/L BDE-47 group was higher than that in the 25, 18.75, 7.5, 2.5 µmol/L BDE-47 group and the positive control group ( P<0.05 ). The mRNA expression of adiponectin in the 12.5, 7.5 µmol/L BDE-47 group and the positive control group was higher than that in the negative control group ( P<0.05 ). The mRNA expression of adiponectin in the 12.5 µmol/L BDE-47 group was higher than that in the 25, 18.75, 2.5 µmol/L BDE-47 group ( P<0.05 ). The mRNA expression of PPARγ and adiponectin in the different concentration groups of BDE-47 distributed like inverted "U" shape. Conclusion BDE-47 can promote the differentiation of 3T3-L1 preadipocytes. Low concentration of BDE-47 may induce adipocyte differentiation by activating PPARγ.
[1] JUNG H O,FATIH K,JUNG I L,et al.Artemisia princeps inhibits adipogenic differentiation of 3T3-L1 pre-adipocytes via downregulation of PPARγ and MAPK pathways[J].Prev Nutr Food Sci,2019,24(3):299-307. [2] FARMER S R.Regulation of PPAR gamma activity during adipogenesis[J]. Int J Obes(Lond),2005,29(Suppl.1):S13-S16. [3] 马武仁,卿颖,李子琪,等.食品中典型持久性有机污染物暴露及毒性通路研究进展[J].中华预防医学杂志,2019,53(6):645-652. [4] WISEMAN S B,WAN Y,CHANG H,et al.Polybrominated diphenyl ethers and their hydroxylated/methoxylated analogs: environmental sources, metabolic relationships, and relative toxicities[J].Mar Pollut Bull,2011,63(5/6/7/8/9/10/11/12):179-188. [5] 翟金霞,童世庐.多溴联苯醚的健康效应研究进展[J].中华预防医学杂志,2016,50(6):559-562. [6] SALES L B,KAMSTRA J H,CENIJN P H,et al.Effects of endocrine disrupting chemicals on in vitro global DNA methylation and adipocyte differentiation[J].Toxicology In Vitro,2013,27(6):1634-1643. [7] 于雪. 利用MTT/MTS法和细胞成像技术评价fHMSN的载药性及AC对细胞增殖的影响[D].长春:吉林大学,2017. [8] TUNG E W Y,BOUDREAU A,WADE M G,et al.Induction of adipocyte differentiation by polybrominated diphenyl ethers (PBDEs) in 3T3-L1 Cells[J/OL].PLoS One,2014,9(4):e94583. [2021-03-31].https://pubmed.ncbi.nlm.nih.gov/24722056/.DOI: 10.1371/journal.pone.0094583. [9] KASSOTIS C,HOFFMAN K,STAPLETON H M.Characterization of adipogenic activity of house dust extracts and semi-volatile indoor contaminants in 3T3-L1 cells[J].Environ Sci Technol,2017,51(15):8735-8745. [10] YANG C,ZHU L,KANG Q,et al.Chronic exposure to tetrabromodiphenyl ether (BDE-47) aggravates hepatic steatosis and liver fibrosis in diet-induced obese mice[J/OL].J Hazard Mater,2019,378:120766. [2021-03-31]. https://pubmed.ncbi.nlm.nih.gov/31226595/.DOI: 10.1016/j.jhazmat.2019.120766. [11] MARION-LETELLIER R,SAVOYE G,GHOSH S.Fatty acids, eicosanoids and PPAR gamma[J].Eur J Pharmacol,2016,785:44-49. [12] AL-GHADBAN S,DIAZ Z T,SINGER H J,et al.Increase in leptin and PPAR-γ gene expression in lipedema adipocytes differentiated in vitro from adipose-derived stem cells[J/OL].Cells,2020,9(2):430. [2021-03-31]. https://pubmed.ncbi.nlm.nih.gov/32059474/.DOI: 10.3390/cells9020430. [13] WANG Y,WANG X H,LI R X.Interaction between peroxisome proliferator-activated receptor gamma polymorphism and overweight on diabetic retinopathy in a Chinese case-control study[J].Int J Clin Exp Med,2015,8(11):21647-21652. [14] 宋琪,司婧,张蕴晖.孕期多溴联苯醚暴露与胎儿发育不良关联的研究进展[J].环境与职业医学,2017,34(12):1105-1110. [15] FANG M L,WEBSTER T F,FERGUSON P L, et al.Characterizing the peroxisome proliferator-activated receptor (PPARγ) ligand binding potential of several major flame retardants, their metabolites, and chemical mixtures in house dust[J].Environ Health Perspect,2015,123(2):166-172. [16] KAMSTRA J H,HRUBA E,BLUMBERS B,et al.Transcriptional and epigenetic mechanisms underlying enhanced in vitro adipocyte differentiation by the brominated flame retardant BDE-47[J].Environ Sci Technol,2014,48(7):4110-4119. [17] 杨晓萌,周丽平,邓洁琳,等.脂联素降低右侧星状神经节活性抑制心肌梗死后室性心律失常[J].中华心律失常学杂志,2020,24(1):66-72. [18] ISHTIAQ S M,RASHID H,HUSSAIN Z,et al.Adiponectin and PPAR: a setup for intricate crosstalk between obesity and non-alcoholic fatty liver disease[J].Rev Endocr Metab Disord,2019,20(3):253-261. [19] SHERRIER M,LI H S.The impact of keto-adaptation on exercise performance and the role of metabolic-regulating cytokines[J].American J Clin Nutr,2019,110(3):562-573. [20] YANG C X,WONG C M,WEI J T,et al.The brominated flame retardant BDE 47 upregulates purine metabolism and mitochondrial respiration to promote adipocyte differentiation[J].Sci Total Environ,2018,644:1312-1322.
