Adrenal stress hormone regulation of hepatic homeostatic function after an acute ozone exposure

ABSTRACT: Ozone-induced lung injury/inflammation and pulmonary/hypothalamus gene expression are diminished in adrenalectomized (ADREX) rats. Acute ozone exposure induces metabolic alterations concomitant with increases in epinephrine and corticosterone. We hypothesized that adrenal hormones are responsible for observed hepatic ozone effects, and in ADREX rats, these changes would be diminished. Five-seven days after sham or ADREX surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4-hrs. Serum samples were analyzed for metabolites and liver for transcriptional changes immediately post-exposure. Ozone increased circulating triglycerides, cholesterol, free fatty acids, and leptin in sham but not ADREX rats. Ozone-induced inhibition of glucose-mediated insulin release was reversed in ADREX rats. Unlike diminution of hypothalamus and lung mRNA expression changes, ADREX in air-exposed rats (ADREX-air/sham-air) caused differential expression of ~1000 genes in liver. Likewise, ~1000 genes were differentially expressed in ozone-exposed ADREX rats (ADREX-ozone/ADREX-air). Ozone-induced hepatic changes in sham rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified significant similarity to glucocorticoids and pathways involving CREBBP. These changes were absent in ADREX rats exposed to ozone. However, ozone caused unique changes in ADREX liver mRNA reflecting activation of synaptogenesis, neurovascular coupling, neuroinflammation, and insulin signaling with inhibition of senescence pathways. In these rats, upstream predictor analysis identified numerous microRNAs involved under glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and the need for further research elucidating their role in propagating environmentally driven diseases.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE196818 | GEO | 2022/11/02

REPOSITORIES: GEO