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Early gestational exposure to ozone increases caloric consumption in male and female peri-adolescent offspring when challenged with a high fat diet
Citation:
Miller, C., E. Stewart, Kathy Mcdaniel, P. Phillips, M. Schladweiler, J. Richards, M. Valdez, C. Gordon, U. Kodavanti, AND J. Dye. Early gestational exposure to ozone increases caloric consumption in male and female peri-adolescent offspring when challenged with a high fat diet. Experimental Biology, San Diego, California, April 21 - 25, 2018.
Impact/Purpose:
We have previously demonstrated that acute exposure to the air pollutant, ozone, in early pregnancy results in reduced fetal growth. Utilizing this same model, we sought to explore the risk of obesity in early adulthood in offspring that were prenatally exposed to ozone during implantation.
Description:
Offspring that are growth restricted at birth have increased risk of infant mortality and cardiometabolic disease as they mature. We have previously demonstrated that acute exposure to the air pollutant, ozone, in early pregnancy results in reduced fetal growth. Utilizing this same model, we sought to explore the risk of obesity in early adulthood in offspring that were prenatally exposed to ozone during implantation. Pregnant, Long-Evans rats were exposed to filtered air or 0.8 ppm ozone, 4 hours/day on gestational day 5 and 6. Peri-adolescent (~post-natal day, PND, 45) male and female offspring from the aforementioned dams were fed either a 10% low-fat diet (LFD) or 45% high-fat diet (HFD) for 72 hours. Food intake, body weight gain, and changes in body composition were monitored during this time period. Basal metabolic rate was determined for the final 24 hours of the diet challenge. At birth, offspring from ozone-exposed pregnancies were approximately 4-7% smaller than control litters. By PND 4, males from ozone pregnancies caught up in weight to that of control males, and by PND 34 had become heavier than controls (~4%). Female offspring from ozone pregnancies remained smaller than control females until ~PND 22. A significant effect of prenatal ozone exposure was found in both grams and calories consumed over 72 hours in male and female offspring. When both sexes were challenged with a HFD, rats from ozone-exposed pregnancies consumed more calories than LFD-fed rats (~30% kcal increase). Although increased caloric consumption did not increase body weight gain in either sex of the ozone-exposed offspring, males of the ozone-exposed, HFD-group had increased fat deposition over the 72-hour period compared to both LFD-fed groups (~290% increase). Measurement of basal metabolic rate indicated that all rats increased fat metabolism, without an effect of prenatal ozone exposure, when fed a 72-hour HFD. However, a significant effect of prenatal ozone to reduce metabolic rate during the light cycle was observed in female offspring. Taken together, these data suggest that ozone exposure early in gestation disrupted energy balance in adolescence. Because both food intake and metabolic rate are regulated within the hypothalamus, we postulate that the prenatal growth restriction observed in our model was associated with disrupted hypothalamic development. Moreover, the increase in caloric intake observed in ozone-exposed offspring may serve to increase the risk of obesity, particularly in males. This abstract does not reflect U.S. EPA policy.