Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction.

Autor: Alewel DI; Oak Ridge Institute for Science and Education Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA., Rentschler KM; Oak Ridge Institute for Science and Education Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA., Jackson TW; Oak Ridge Institute for Science and Education Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, NC, USA., Schladweiler MC; Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, 109 T.W. Alexander Dr., Research Triangle Park, NC, 27711, USA., Astriab-Fisher A; Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, 109 T.W. Alexander Dr., Research Triangle Park, NC, 27711, USA., Evansky PA; Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, 109 T.W. Alexander Dr., Research Triangle Park, NC, 27711, USA., Kodavanti UP; Public Health and Integrated Toxicology Division, Center for Public Health and Environmental Assessment, U.S. Environmental Protection Agency, 109 T.W. Alexander Dr., Research Triangle Park, NC, 27711, USA. kodavanti.urmila@epa.gov.
Jazyk: angličtina
Zdroj: Scientific reports [Sci Rep] 2023 Dec 01; Vol. 13 (1), pp. 21179. Date of Electronic Publication: 2023 Dec 01.
DOI: 10.1038/s41598-023-48413-w
Abstrakt: Acrolein, a respiratory irritant, induces systemic neuroendocrine stress. However, peripheral metabolic effects have not been examined. Male and female WKY rats were exposed to air (0 ppm) or acrolein (3.16 ppm) for 4 h, followed by immediate serum and liver tissue collection. Serum metabolomics in both sexes and liver transcriptomics in males were evaluated to characterize the systemic metabolic response. Of 887 identified metabolites, > 400 differed between sexes at baseline. An acrolein biomarker, 3-hydroxypropyl mercapturic acid, increased 18-fold in males and 33-fold in females, indicating greater metabolic detoxification in females than males. Acrolein exposure changed 174 metabolites in males but only 50 in females. Metabolic process assessment identified higher circulating free-fatty acids, glycerols, and other lipids in male but not female rats exposed to acrolein. In males, acrolein also increased branched-chain amino acids, which was linked with metabolites of nitrogen imbalance within the gut microbiome. The contribution of neuroendocrine stress was evident by increased corticosterone in males but not females. Male liver transcriptomics revealed acrolein-induced over-representation of lipid and protein metabolic processes, and pathway alterations including Sirtuin, insulin-receptor, acute-phase, and glucocorticoid signaling. In sum, acute acrolein inhalation resulted in sex-specific serum metabolomic and liver transcriptomic derangement, which may have connections to chronic metabolic-related diseases.
(© 2023. This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply.)
Databáze: MEDLINE
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