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Influences of Peri-Implantation Ozone Exposure and Post-Natal High Fat Diet on Energy Balance and Hypothalamic DNA Methylation.
Citation:
Miller, C., E. Stewart, Kathy Mcdaniel, P. Phillips, J. Richards, M. Schladweiler, M. Valdez, C. Gordon, U. Kodavanti, AND J. Dye. Influences of Peri-Implantation Ozone Exposure and Post-Natal High Fat Diet on Energy Balance and Hypothalamic DNA Methylation. ENDO2019, New Orleans, Lousianna, March 23 - 26, 2019.
Impact/Purpose:
Ozone exposure during implantation receptivity reduces fetal growth during gestation. Intrauterine growth restriction is associated with increased metabolic disease risk as offspring age into adulthood. Therefore, the purpose of this study was to investigate the risk of obesity in offspring from ozone-exposed dams.
Description:
Ozone exposure during implantation receptivity reduces fetal growth during gestation. Intrauterine growth restriction is associated with increased metabolic disease risk as offspring age into adulthood. Therefore, the purpose of this study was to investigate the risk of obesity in offspring from ozone-exposed dams. Long-Evans dams were exposed to filtered air or 0.8 ppm ozone for 4-hours on gestation days 5 and 6. To assess metabolic risk, subsets of peri-adolescent offspring were fed a 45% high-fat diet (HFD) for 3-days, which is an established model of acute leptin and insulin resistance in rats. Over the 3-day challenge, HFD-fed offspring from ozone-exposed dams consumed more calories and had reduced metabolic rate compared to their low-fat diet (LFD)-fed controls. Accordingly, HFD-fed males from ozone-exposed dams had a nearly 300% increase in fat accrual compared to controls, whereas females failed to exhibit this response. Analysis of hypothalamic gene expression found reductions in the appetite-regulating genes including insulin receptor (Insr) and cocaine and amphetamine regulated transcript (Cartpt) in male offspring from ozone-exposed dams fed HFD. Gene-specific DNA methylation was performed using MeDIP-qPCR. Neither prenatal ozone nor HFD affected methylation of Insr or Cartpt in males. However, prenatal ozone exposure increased DNA methylation of Insr in females, which occurred without a decrease in Insr transcript. Together, our data suggest that a relatively acute exposure to ozone in early pregnancy alters energy balance in the offspring, the mechanisms and consequences of which is likely to be sex specific. Abstract does not reflect US EPA policy.