Altered Transcriptomic Effects of Ozone Across the Brain Following Maternal High Fat Diet
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Obesity affects more than one-third of US adults and is one of the leading causes of preventable death. Previously, we have found that dams fed a high fat diet (HFD) for 6-weeks prior to breeding and through postnatal day (PND) 32, generated offspring with significantly elevated susceptibility to ozone (O3) when exposed as adults. We concluded that poor maternal diet choices may alter offspring's susceptibility to air pollutants. We hypothesized that maternal HFD would alter the transcriptome of the hypothalamus (HYP) and impact the effect of O3 on global gene expression in both HYP and hippocampus (HIP). A 6-week pre-breeding HFD treatment was performed alongside a control diet (CD) on Long Evans dams and continued through PND 30 when all offspring were switched to control diet. At PND 40, rats were exposed to filtered air or ozone (0.8 ppm for 5 hr), followed by necropsy. Total isolated RNA (RIN score > 6) was prepped for using a PrepX RNA-Seq kit (Takara) and sequenced on an Illumina NextSeq 500 for 75 single-read cycles. Sequencing data was aligned to rn6 Ensemble Transcripts (r97), outliers identified by principal components analysis, and differentially expressed genes (DEGs) were determined by DEseq2 using a false discovery rate cutoff of <0.05. In the HYP, HFD increased expression of PCDH20, which encodes for a non-clustered protocadherin involved in neuronal diseases. O3 exposure blocked this increase. HFD also increased expression of ACADSB in the HYP, which is involved in dietary protein processing. Exposure to O3 reversed this expression. Within the HYP of CD, O3 exposure resulted in 17 DEGs, 11 of which were also altered in the HYP of HFD exposed to O3. In the HIP, the O3 induced only 7 ozone-mediated DEGs identified in CD. O3 influenced the expression of the majority of the DEGs. The most consistent effect of ozone across both brain regions was an increased expression of the lipid droplet storage factor, Plin4. These results indicate that ozone induces changes in gene expression in both the HYP and HIP and maternal diet may interact with these expressions. (This abstract does not necessarily reflect US EPA policy).