den Broeder Marjo J, Moester Miriam J B, Kamstra Jorke H, Cenijn Peter H, Davidoiu Valentina, Kamminga Leonie M, Ariese Freek, de Boer Johannes F, Legler Juliette
Institute of Environmental, Health and Societies, Brunel University, UB8 3PH London, UK.
Institute for Environmental Studies, Vrije Universiteit Amsterdam, 1081 HV Amsterdam, The Netherlands.
Int J Mol Sci. 2017 Apr 24;18(4):894. doi: 10.3390/ijms18040894.
Early life stage exposure to environmental chemicals may play a role in obesity by altering adipogenesis; however, robust in vivo methods to quantify these effects are lacking. The goal of this study was to analyze the effects of developmental exposure to chemicals on adipogenesis in the zebrafish (). We used label-free Stimulated Raman Scattering (SRS) microscopy for the first time to image zebrafish adipogenesis at 15 days post fertilization (dpf) and compared standard feed conditions (StF) to a high fat diet (HFD) or high glucose diet (HGD). We also exposed zebrafish embryos to a non-toxic concentration of tributyltin (TBT, 1 nM) or Tris(1,3-dichloroisopropyl)phosphate (TDCiPP, 0.5 µM) from 0-6 dpf and reared larvae to 15 dpf under StF. Potential molecular mechanisms of altered adipogenesis were examined by qPCR. Diet-dependent modulation of adipogenesis was observed, with HFD resulting in a threefold increase in larvae with adipocytes, compared to StF and HGD. Developmental exposure to TBT but not TDCiPP significantly increased adipocyte differentiation. The expression of adipogenic genes such as , and was altered in response to HFD or chemicals. This study shows that SRS microscopy can be successfully applied to zebrafish to visualize and quantify adipogenesis, and is a powerful approach for identifying obesogenic chemicals in vivo.
生命早期阶段暴露于环境化学物质可能通过改变脂肪生成而在肥胖中起作用;然而,缺乏可靠的体内方法来量化这些影响。本研究的目的是分析发育期暴露于化学物质对斑马鱼脂肪生成的影响。我们首次使用无标记受激拉曼散射(SRS)显微镜对受精后15天(dpf)的斑马鱼脂肪生成进行成像,并将标准饲料条件(StF)与高脂饮食(HFD)或高糖饮食(HGD)进行比较。我们还在0至6 dpf期间将斑马鱼胚胎暴露于无毒浓度的三丁基锡(TBT,1 nM)或磷酸三(1,3 - 二氯异丙基)酯(TDCiPP,0.5 µM),并在StF条件下将幼虫饲养至15 dpf。通过定量PCR研究脂肪生成改变的潜在分子机制。观察到脂肪生成的饮食依赖性调节,与StF和HGD相比,HFD导致具有脂肪细胞的幼虫增加了三倍。发育期暴露于TBT而非TDCiPP显著增加了脂肪细胞分化。诸如 、 和 等脂肪生成基因 的表达因HFD或化学物质而改变。本研究表明,SRS显微镜可成功应用于斑马鱼以可视化和量化脂肪生成,并且是一种在体内识别致肥胖化学物质的有力方法。 (注:原文中部分基因名称未给出具体内容,用“ ”表示)