Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, US Environmental Protection Agency, 109 T.W. Alexander Dr. Research Triangle Park, Durham, NC, USA.
ICF Inc, Durham, NC, USA.
Sci Rep. 2020 Oct 1;10(1):16353. doi: 10.1038/s41598-020-73361-0.
The influence of maternal high-fat diet (HFD) on metabolic response to ozone was examined in Long-Evans rat offspring. F0 females were fed control diet (CD; 10%kcal from fat) or HFD (60%kcal from fat) starting at post-natal day (PND) 30. Rats were bred on PND 72. Dietary regimen was maintained until PND 30 when all offspring were switched to CD. On PND 40, F1 offspring (n = 10/group/sex) were exposed to air or 0.8 ppm ozone for 5 h. Serum samples were collected for global metabolomic analysis (n = 8/group/sex). Offspring from HFD dams had increased body fat and weight relative to CD. Metabolomic analysis revealed significant sex-, diet-, and exposure-related changes. Maternal HFD increased free fatty acids and decreased phospholipids (male > female) in air-exposed rats. Microbiome-associated histidine and tyrosine metabolites were increased in both sexes, while 1,5-anhydroglucitol levels decreased in males indicating susceptibility to insulin resistance. Ozone decreased monohydroxy fatty acids and acyl carnitines and increased pyruvate along with TCA cycle intermediates in females (HFD > CD). Ozone increased various amino acids, polyamines, and metabolites of gut microbiota in HFD female offspring indicating gut microbiome alterations. Collectively, these data suggest that maternal HFD increases offspring susceptibility to metabolic alterations in a sex-specific manner when challenged with environmental stressors.
本研究旨在探讨母体高脂肪饮食（HFD）对后代代谢对臭氧反应的影响。从产后第 30 天（PND30）开始，F0 雌性大鼠分别喂食对照饮食（CD；10%的热量来自脂肪）或 HFD（60%的热量来自脂肪）。在 PND72 时进行配种，饮食方案一直维持到 PND30，此时所有后代均切换为 CD。在 PND40 时，F1 后代（n=10/组/性别）暴露于空气或 0.8ppm 臭氧中 5 小时。收集血清样本进行代谢组学分析（n=8/组/性别）。与 CD 相比，来自 HFD 母鼠的后代体脂和体重增加。代谢组学分析显示，存在显著的性别、饮食和暴露相关变化。HFD 增加了空气暴露大鼠的游离脂肪酸和磷脂（雄性>雌性）。微生物组相关的组氨酸和酪氨酸代谢物在两性中增加，而 1,5-脱水葡萄糖醇水平在雄性中降低，表明易发生胰岛素抵抗。臭氧降低了单羟基脂肪酸和酰基辅酶 A，并增加了雌性中的丙酮酸以及 TCA 循环中间产物（HFD>CD）。臭氧增加了各种氨基酸、多胺和肠道微生物群代谢物，表明肠道微生物群发生了改变。总之，这些数据表明，母体 HFD 增加了后代对环境应激的代谢改变的易感性，且具有性别特异性。
