The Influence of Maternal High Fat Diet and Ozone Exposure on Serum Metabolomic Profiles in Juvenile Offspring
Authors: Snow Samantha J. , Gordon Chris , Phillips Pam , Schladweiler Mette , Ledbetter Allen , Henriquez Andres , Miller Colette , Broniowska Kasia , Karoly Ed , Kodavanti Urmila 
Published: June 2021

There is growing interest in understanding how maternal diet can affect the sensitivity of offspring to environmental exposures. Previous studies have demonstrated that adult offspring from dams given a high fat diet (HFD) prior to, during, and after pregnancy had elevated pulmonary responses to an acute ozone exposure. In this study, we examined the influence of maternal HFD on metabolic responses to ozone in male and female juvenile offspring. F0 female Long Evans rats began HFD (60% kcal from fat) or control diet (CD; 10.5% kcal from fat) at post‐natal day (PND) 30. Rats were bred on PND 75 and allowed to give birth. F1 litters were culled at PND 6 and offspring were weaned on PND 21. Offspring were maintained on respective HFD or CD until PND 30 when all groups were switched to CD. On PND 40, male and female offspring (n=8/group) were exposed to air or 0.8 ppm ozone for 5h. Immediately following exposure, animals were necropsied, serum was collected, and samples were subsequently assessed for changes in metabolite abundance using a metabolomic approach. Overall, analysis revealed significant changes in circulating metabolites due to sex, diet, and exposure. Maternal HFD increased serum microbiome‐associated histidine metabolites in male and tyrosine metabolites in female offspring, whereas selected free fatty acids were increased and phospholipids were decreased in both sexes. Furthermore, lower levels of 1,5‐anhydroglucitol were observed in all HFD groups regardless of sex or exposure. During hyperglycemic episodes, this metabolite is competitively inhibited by glucose for renal tubular reabsorption, thus decreases here may point towards development of insulin resistance in the offspring of mothers fed the HFD. Ozone exposure also had significant effects on serum metabolites. Decreases in biliverdin and bilirubin, heme catabolites with antioxidant properties, were detected in ozone‐exposed male and female offspring fed the CD but not the HFD, suggesting that the maternal diet may impact heme metabolism in offspring. Increases in free polyunsaturated fatty acids (PUFAs) were observed in ozone‐exposed male rats whereas in the female HFD ozone group, decreases in free PUFAs and monounsaturated fatty acids were apparent. Moreover, exposure to ozone led to increased levels of glucose in male rats regardless of maternal diet; however, in female offspring, pyruvate levels were elevated suggesting an increase in glucose utilization. This is supported by an ozone‐induced increase in the TCA cycle intermediates citrate and isocitrate in the female offspring of the HFD group. Collectively, the dataset suggest that ozone exposure elicits greater metabolic impact in juvenile female than male rats, and that maternal diet may further potentiate this effect. These results represent the basis to study the effects of maternal HFD on offspring sensitivity towards environmental factors and clearly suggest that susceptibility to ozone‐induced injury is sex‐dependent. (This abstract does not reflect US EPA Policy)Support or Funding InformationThis work was supported by US EPA funds.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.