Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults.
Dysregulated lipid and fatty acid metabolism link perfluoroalkyl substances exposure and impaired glucose metabolism in young adults.
复制标题
DOI：
10.1016/j.envint.2020.106091
复制
发表时间：
2020-12
影响因子：
11.8
通讯作者：
Gilliland FD
中科院分区：
文献类型：
--
作者：
Chen Z;Yang T;Walker DI;Thomas DC;Qiu C;Chatzi L;Alderete TL;Kim JS;Conti DV;Breton CV;Liang D;Hauser ER;Jones DP;Gilliland FD
全氟烷基和多氟烷基物质（PFAS）暴露在美国人口中普遍存在，并与不良健康后果有关，包括心脏代谢疾病，免疫失调和内分泌干扰。然而，PFAS暴露对健康不利影响的代谢机制尚不清楚。该项目的目的是调查PFAS暴露与年轻人心脏代谢风险增加相关的代谢途径改变之间的关联。在2014年至2017年期间，共有102名来自南加州的年轻人参加了研究，其中82%的人超重或肥胖。心脏代谢结果进行了评估，包括口服葡萄糖耐量试验（OGTT）的措施，身体脂肪和血脂谱。高分辨率代谢组学被用来量化血浆暴露水平的三个PFAS同系物和强度分布的非靶向代谢。使用参与脂肪酸和脂质代谢的45种靶向代谢物的空腹浓度来验证非靶向代谢组学结果。贝叶斯核机器回归（BKMR）用于检查PFAS暴露混合物与调整协变量的心脏代谢结果之间的关联。Mummichog途径富集分析用于探索PFAS相关的代谢途径。此外，研究了PFAS暴露对代谢网络的影响，包括代谢组学特征和心脏代谢结果。全氟辛酸（PFOA）的高暴露量与OGTT期间较高的30分钟血糖水平和血糖曲线下面积（AUC）相关（p < 0.001）。PFAS暴露也与脂质途径的改变有关，这有助于连接PFOA和OGTT后更高的葡萄糖水平的代谢网络。靶向代谢组学分析表明，较高的PFOA暴露与较高的甘油水平相关（p = 0.006），甘油本身与较高的30分钟葡萄糖相关（p = 0.006）。增加脂肪分解和脂肪酸氧化可能有助于连接PFAS暴露和葡萄糖代谢受损的年轻人的生物学机制。这项研究的结果值得未来的实验研究和流行病学研究与更大的样本量来复制。
Per- and polyfluoroalkyl substances (PFASs) exposure is ubiquitous among the US population and has been linked to adverse health outcomes including cardiometabolic diseases, immune dysregulation and endocrine disruption. However, the metabolic mechanism underlying the adverse health effect of PFASs exposure is unknown. The aim of this project is to investigate the association between PFASs exposure and altered metabolic pathways linked to increased cardiometabolic risk in young adults. A total of 102 young adults with 82% overweight or obese participants were enrolled from Southern California between 2014 and 2017. Cardiometabolic outcomes were assessed including oral glucose tolerance test (OGTT) measures, body fat and lipid profiles. High-resolution metabolomics was used to quantify plasma exposure levels of three PFAS congeners and intensity profiles of the untargeted metabolome. Fasting concentrations of 45 targeted metabolites involved in fatty acid and lipid metabolism were used to verify untargeted metabolomics findings. Bayesian Kernel Machine Regression (BKMR) was used to examine the associations between PFAS exposure mixture and cardiometabolic outcomes adjusting for covariates. Mummichog pathway enrichment analysis was used to explore PFAS-associated metabolic pathways. Moreover, the effect of PFAS exposure on the metabolic network, including metabolomic profiles and cardiometabolic outcomes, was investigated. Higher exposure to perfluorooctanoic acid (PFOA) was associated with higher 30-minute glucose levels and glucose area under the curve (AUC) during the OGTT (p < 0.001). PFAS exposure was also associated with altered lipid pathways, which contributed to the metabolic network connecting PFOA and higher glucose levels following the OGTT. Targeted metabolomics analysis indicated that higher PFOA exposure was associated with higher levels of glycerol (p = 0.006), which itself was associated with higher 30-minute glucose (p = 0.006). Increased lipolysis and fatty acid oxidation could contribute to the biological mechanisms linking PFAS exposure and impaired glucose metabolism among young adults. Findings of this study warrants future experimental studies and epidemiological studies with larger sample size to replicate.
登录
查看更多内容
影响因子：
5.6
作者：
Lamichane S;Dahal Lamichane B;Kwon SM
通讯作者：
Kwon SM
影响因子：
11.8
作者：
Alderete, Tanya L.;Jin, Ran;Chatzi, Lida
通讯作者：
Chatzi, Lida
影响因子：
16.2
作者：
Domazet, Sidsel L.;Grontved, Anders;Jensen, Tina K.
通讯作者：
Jensen, Tina K.
影响因子：
6
作者：
Liu, Gang;Zhang, Bo;Sun, Qi
通讯作者：
Sun, Qi
DOI：
10.1016/j.ijheh.2013.03.008
发表时间：
2014-01-01
影响因子：
6
作者：
Jain, Ram B.
通讯作者：
Jain, Ram B.