Miller Desinia B, Ghio Andrew J, Karoly Edward D, Bell Lauren N, Snow Samantha J, Madden Michael C, Soukup Joleen, Cascio Wayne E, Gilmour M Ian, Kodavanti Urmila P
1 Curriculum in Toxicology, University of North Carolina-Chapel Hill, Chapel Hill, North Carolina.
2 Environmental Public Health Division, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina; and.
Am J Respir Crit Care Med. 2016 Jun 15;193(12):1382-91. doi: 10.1164/rccm.201508-1599OC.
Air pollution has been associated with increased prevalence of type 2 diabetes; however, the mechanisms remain unknown. We have shown that acute ozone exposure in rats induces release of stress hormones, hyperglycemia, leptinemia, and glucose intolerance that are associated with global changes in peripheral glucose, lipid, and amino acid metabolism.
To examine ozone-induced metabolic derangement in humans using serum metabolomic assessment, establish human-to-rodent coherence, and identify novel nonprotein biomarkers.
Serum samples were obtained from a crossover clinical study that included two clinic visits (n = 24 each) where each subject was blindly exposed in the morning to either filtered air or 0.3 parts per million ozone for 2 hours during 15-minute on-off exercise. Serum samples collected within 1 hour after exposure were assessed for changes in metabolites using a metabolomic approach.
Metabolomic analysis revealed that ozone exposure markedly increased serum cortisol and corticosterone together with increases in monoacylglycerol, glycerol, and medium- and long-chain free fatty acids, reflective of lipid mobilization and catabolism. Additionally, ozone exposure increased serum lysolipids, potentially originating from membrane lipid breakdown. Ozone exposure also increased circulating mitochondrial β-oxidation-derived metabolites, such as acylcarnitines, together with increases in the ketone body 3-hydroxybutyrate. These changes suggested saturation of β-oxidation by ozone in exercising humans.
As in rodents, acute ozone exposure increased stress hormones and globally altered peripheral lipid metabolism in humans, likely through activation of a neurohormonally mediated stress response pathway. The metabolomic assessment revealed new biomarkers and allowed for establishment of rodent-to-human coherence. Clinical trial registered with www.clinicaltrials.gov (NCT 01492517).
空气污染与2型糖尿病患病率增加有关；然而，其机制仍不清楚。我们已经表明，大鼠急性暴露于臭氧会诱导应激激素释放、高血糖、瘦素血症和葡萄糖不耐受，这些与外周葡萄糖、脂质和氨基酸代谢的整体变化有关。
通过血清代谢组学评估检查臭氧诱导的人类代谢紊乱，建立人与啮齿动物的一致性，并识别新的非蛋白质生物标志物。
血清样本取自一项交叉临床研究，该研究包括两次临床就诊（每次n = 24），在每次就诊时，每位受试者在早晨15分钟开-关运动期间，被盲目暴露于过滤空气或百万分之0.3的臭氧中2小时。使用代谢组学方法评估暴露后1小时内收集的血清样本中代谢物的变化。
代谢组学分析显示，臭氧暴露显著增加血清皮质醇和皮质酮，同时单酰甘油、甘油以及中链和长链游离脂肪酸增加，这反映了脂质动员和分解代谢。此外，臭氧暴露增加血清溶血脂质，可能源自膜脂质分解。臭氧暴露还增加循环线粒体β-氧化衍生的代谢物，如酰基肉碱，同时酮体3-羟基丁酸增加。这些变化表明运动中的人β-氧化被臭氧饱和。
与啮齿动物一样，急性臭氧暴露增加人类应激激素并整体改变外周脂质代谢，可能是通过激活神经激素介导的应激反应途径。代谢组学评估揭示了新的生物标志物，并建立了啮齿动物与人的一致性。临床试验已在www.clinicaltrials.gov注册（NCT 01492517）。
