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

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...

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Autores principales: Alewel, Devin I., Rentschler, Katherine M., Jackson, Thomas W., Schladweiler, Mette C., Astriab-Fisher, Anna, Evansky, Paul A., Kodavanti, Urmila P.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692194/
https://www.ncbi.nlm.nih.gov/pubmed/38040807
http://dx.doi.org/10.1038/s41598-023-48413-w
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author Alewel, Devin I.
Rentschler, Katherine M.
Jackson, Thomas W.
Schladweiler, Mette C.
Astriab-Fisher, Anna
Evansky, Paul A.
Kodavanti, Urmila P.
author_facet Alewel, Devin I.
Rentschler, Katherine M.
Jackson, Thomas W.
Schladweiler, Mette C.
Astriab-Fisher, Anna
Evansky, Paul A.
Kodavanti, Urmila P.
author_sort Alewel, Devin I.
collection PubMed
description 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.
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spelling pubmed-106921942023-12-03 Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction Alewel, Devin I. Rentschler, Katherine M. Jackson, Thomas W. Schladweiler, Mette C. Astriab-Fisher, Anna Evansky, Paul A. Kodavanti, Urmila P. Sci Rep Article 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. Nature Publishing Group UK 2023-12-01 /pmc/articles/PMC10692194/ /pubmed/38040807 http://dx.doi.org/10.1038/s41598-023-48413-w Text en © This is a U.S. Government work and not under copyright protection in the US; foreign copyright protection may apply 2023 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Alewel, Devin I.
Rentschler, Katherine M.
Jackson, Thomas W.
Schladweiler, Mette C.
Astriab-Fisher, Anna
Evansky, Paul A.
Kodavanti, Urmila P.
Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction
title Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction
title_full Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction
title_fullStr Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction
title_full_unstemmed Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction
title_short Serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction
title_sort serum metabolome and liver transcriptome reveal acrolein inhalation-induced sex-specific homeostatic dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10692194/
https://www.ncbi.nlm.nih.gov/pubmed/38040807
http://dx.doi.org/10.1038/s41598-023-48413-w
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