Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT.
Transgenerational metabolomic fingerprints in mice ancestrally exposed to the obesogen TBT.
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DOI：
10.1016/j.envint.2021.106822
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发表时间：
2021-12
影响因子：
11.8
通讯作者：
Zalko D
中科院分区：
文献类型：
--
作者：
Chamorro-García R;Poupin N;Tremblay-Franco M;Canlet C;Egusquiza R;Gautier R;Jouanin I;Shoucri BM;Blumberg B;Zalko D
内分泌干扰化学物质 (EDC) 会导致肥胖、胰岛素抵抗和肝功能障碍等代谢紊乱的病因。人们越来越关注围产期 EDC 暴露对以后生活中疾病易感性的影响。代谢组学是研究生命早期接触 EDC 的长期后果的有前景的方法。这些方法可以识别和表征直接或祖先暴露的生物标志物，这些生物标志物可以诊断个体对疾病的易感性，并有助于了解 EDC 的作用机制。我们试图鉴定祖先暴露于肥胖原三丁基锡（TBT）模型的小鼠的代谢组指纹，以评估代谢组学是否可以区分潜在的跨代肥胖易感性，并识别由祖先TBT暴露调节的代谢途径。我们使用非靶向 1H NMR 代谢组学分析，对从祖先暴露于 TBT 的雄性和雌性小鼠收集的血浆和肝脏样本进行了两个独立的跨代实验，其中 F3 和 F4 雄性在面临膳食脂肪增加的挑战时变得肥胖。代谢组学在两项独立研究中证实了环境相关剂量的 TBT 对 F3 和 F4 雄性的跨代肥胖效应。尽管雌性小鼠从未变得肥胖，但其特定的代谢组学指纹证明了 TBT 对雌性小鼠的明显跨代影响，这与肝脏生物转化能力受损相一致。这项研究是代谢组学首次应用来揭示 EDC 暴露的跨代影响。很早就在祖先接触过 TBT 的动物中观察到血浆代谢组发生显着变化。这些变化先于 TBT 组中膳食脂肪增加引起的肥胖效应发生，并最终导致肝脏代谢组发生显着变化。代谢组指纹的开发可以促进识别携带祖先肥胖原暴露特征的个体，这可能会增加他们对其他危险因素（例如膳食脂肪增加）的易感性。
Endocrine disrupting chemicals (EDCs) contribute to the etiology of metabolic disorders such as obesity, insulin resistance and hepatic dysfunction. Concern is growing about the consequences of perinatal EDC exposure on disease predisposition later in life. Metabolomics are promising approaches for studying long-term consequences of early life EDC exposure. These approaches allow for the identification and characterization of biomarkers of direct or ancestral exposures that could be diagnostic for individual susceptibility to disease and help to understand mechanisms through which EDCs act. We sought to identify metabolomic fingerprints in mice ancestrally exposed to the model obesogen tributyltin (TBT), to assess whether metabolomics could discriminate potential trans-generational susceptibility to obesity and recognize metabolic pathways modulated by ancestral TBT exposure. We used non-targeted 1H NMR metabolomic analyses of plasma and liver samples collected from male and female mice ancestrally exposed to TBT in two independent transgenerational experiments in which F3 and F4 males became obese when challenged with increased dietary fat. Metabolomics confirmed transgenerational obesogenic effects of environmentally relevant doses of TBT in F3 and F4 males, in two independent studies. Although females never became obese, their specific metabolomic fingerprint evidenced distinct transgenerational effects of TBT in female mice consistent with impaired capacity for liver biotransformation. This study is the first application of metabolomics to unveil the transgenerational effects of EDC exposure. Very early, significant changes in the plasma metabolome were observed in animals ancestrally exposed to TBT. These changes preceded the onset of obesogenic effects elicited by increased dietary fat in the TBT groups, and which ultimately resulted in significant changes in the liver metabolome. Development of metabolomic fingerprints could facilitate the identification of individuals carrying the signature of ancestral obesogen exposure that might increase their susceptibility to other risk factor such as increased dietary fat.
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DOI：
10.1146/annurev-pharmtox-010818-021304
发表时间：
2019-01-06
影响因子：
12.5
作者：
Heindel JJ;Blumberg B
通讯作者：
Blumberg B
影响因子：
5.6
作者：
Milton FA;Lacerda MG;Sinoti SBP;Mesquita PG;Prakasan D;Coelho MS;de Lima CL;Martini AG;Pazzine GT;Borin MF;Amato AA;Neves FAR
通讯作者：
Neves FAR
影响因子：
2.5
作者：
Corbin KD;Zeisel SH
通讯作者：
Zeisel SH
影响因子：
10.4
作者：
Chamorro-García R;Shoucri BM;Willner S;Käch H;Janesick A;Blumberg B
通讯作者：
Blumberg B
HIV蛋白酶易感性的蛋白化学调查模型。
影响因子：
3
作者：
Lapins, Maris;Eklund, Martin;Spjuth, Ola;Prusis, Peteris;Wikberg, Jarl E. S.
通讯作者：
Wikberg, Jarl E. S.