Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis
Perfluoroalkyl substances, metabolomic profiling, and alterations in glucose homeostasis among overweight and obese Hispanic children: A proof-of-concept analysis
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DOI：
10.1016/j.envint.2019.02.047
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发表时间：
2019-05-01
影响因子：
11.8
通讯作者：
Chatzi, Lida
中科院分区：
文献类型：
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作者：
Alderete, Tanya L.;Jin, Ran;Chatzi, Lida
目的：为了研究暴露于全氟烷基物质（PFASs）和纵向测量的葡萄糖代谢的高危超重和肥胖的西班牙裔children.Methods：40超重和肥胖的西班牙裔儿童（8-14岁）从城市洛杉矶进行了临床措施和2小时口服葡萄糖耐量试验（OGTT）在基线和随访访视（范围：1-3年后登记）之间的前瞻性关联。基线血浆全氟辛酸（PFOA），全氟辛烷磺酸（PFOS），全氟己烷磺酸（PFHxS），和血浆代谢组测定液相色谱高分辨率质谱。使用多元线性回归模型评估基线PFAS与随访期间葡萄糖稳态变化之间的相关性。进行了一项代谢组范围相关性研究和途径富集分析，以评价与血浆PFAS浓度相关的代谢失调。我们进行了结构综合分析，旨在描述所有因素的联合影响，并根据其暴露和代谢组学特征，确定葡萄糖稳态改变的儿童的潜在集群。（95% CI：8.8-52.4）和10.2 mg/dL（95% CI：2.7-17.7）时，2小时血糖水平分别升高。PFHxS浓度增加ln（ng/ml）也与葡萄糖曲线下面积增加17.8 mg/dL相关（95% CI：1.5-34.1）。途径富集分析显示脂质的显著改变（例如，鞘糖脂、亚油酸和从头脂肪生成），和氨基酸（例如，天冬氨酸和天冬酰胺，酪氨酸，精氨酸和脯氨酸）与PFASs暴露相关。综合分析确定了一个集群的儿童增加2小时的葡萄糖水平超过随访，其特点是增加PFAS水平和改变代谢物patterns.Conclusions：这证明的概念分析表明，较高的PFAS暴露与失调的几个脂质和氨基酸途径和纵向改变葡萄糖稳态在西班牙裔青年。需要更大规模的研究来证实这些发现，并充分阐明潜在的生物学机制。
Objective: To examine the prospective associations between exposure to perfluoroalkyl substances (PFASs) and longitudinal measurements of glucose metabolism in high-risk overweight and obese Hispanic children.Methods: Forty overweight and obese Hispanic children (8-14 years) from urban Los Angeles underwent clinical measures and 2-hour oral glucose tolerance tests (OGTT) at baseline and a follow-up visit (range: 1-3 years after enrollment). Baseline plasma perfluorooctanoic acid (PFOA), perfluorooctane sulfonate (PFOS), perfluorohexane sulfonic acid (PFHxS), and the plasma metabolome were measured by liquid-chromatography with high-resolution mass spectrometry. Multiple linear regression models were used to assess the association between baseline PFASs and changes in glucose homeostasis over follow-up. A metabolome-wide association study coupled with pathway enrichment analysis was performed to evaluate metabolic dysregulation associated with plasma PFASs concentrations. We performed a structural integrated analysis aiming to characterize the joint impact of all factors and to identify latent clusters of children with alterations in glucose homeostasis, based on their exposure and metabolomics profile.Results: Each ln (ng/ml) increase in PFOA and PFHxS concentrations was associated with a 30.6 mg/dL (95% CI: 8.8-52.4) and 10.2 mg/dL (95% CI: 2.7-17.7) increase in 2-hour glucose levels, respectively. A ln (ng/ml) increase in PFHxS concentrations was also associated with 17.8 mg/dL increase in the glucose area under the curve (95% CI: 1.5-34.1). Pathway enrichment analysis showed significant alterations of lipids (e.g., glycosphingolipids, linoleic acid, and de novo lipogenesis), and amino acids (e.g., aspartate and asparagine, tyrosine, arginine and proline) in association to PFASs exposure. The integrated analysis identified a cluster of children with increased 2-h glucose levels over follow up, characterized by increased PFAS levels and altered metabolite patterns.Conclusions: This proof-of-concept analysis shows that higher PFAS exposure was associated with dysregulation of several lipid and amino acid pathways and longitudinal alterations in glucose homeostasis in Hispanic youth. Larger studies are needed to confirm these findings and fully elucidate the underlying biological mechanisms.