Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats
Abstract Ozone-induced lung injury, inflammation, and pulmonary/hypothalamus gene expression changes are diminished in adrenalectomized (AD) rats. Acute ozone exposure induces metabolic alterations concomitant with increases in epinephrine and corticosterone. We hypothesized that adrenal hormones ar...
Gespeichert in:
| Veröffentlicht in: | Toxicological sciences 2022-08, Vol.189 (1), p.73-90 |
|---|---|
| Hauptverfasser: | , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 90 |
|---|---|
| container_issue | 1 |
| container_start_page | 73 |
| container_title | Toxicological sciences |
| container_volume | 189 |
| creator | Jackson, Thomas W Henriquez, Andres R Snow, Samantha J Schladweiler, Mette C Fisher, Anna A Alewel, Devin I House, John S Kodavanti, Urmila P |
| description | Abstract
Ozone-induced lung injury, inflammation, and pulmonary/hypothalamus gene expression changes are diminished in adrenalectomized (AD) 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 AD rats, these changes would be diminished. In total, 5–7 days after sham (SH) or AD surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4 h. 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 SH but not AD rats. Ozone-induced inhibition of glucose-mediated insulin release was absent in AD rats. Unlike diminution of ozone-induced hypothalamus and lung mRNA expression changes, AD in air-exposed rats (AD-air/SH-air) caused differential hepatic expression of ∼1000 genes. Likewise, ozone in AD rats caused differential expression of ∼1000 genes (AD-ozone/AD-air). Ozone-induced hepatic changes in SH rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified similarity to responses produced by glucocorticoids and pathways involving forskolin. These changes were absent in AD rats exposed to ozone. However, ozone caused unique changes in AD 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 likely involved in glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and necessitate further research elucidating their role in propagating environmentally driven diseases. |
| doi_str_mv | 10.1093/toxsci/kfac065 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9609881</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><oup_id>10.1093/toxsci/kfac065</oup_id><sourcerecordid>2680237745</sourcerecordid><originalsourceid>FETCH-LOGICAL-c451t-99892f32f924d7829b1a175bfc798f341aee9b1dc5e79bad96f036221614ad8d3</originalsourceid><addsrcrecordid>eNqFUU1v1DAQjRCIfsCVI7I4wSGtP5LYviCtqpZFFFXiQxwtrzNuDYkdbAd1--vxdkMFJ05-mvfmeWZeVb0g-IRgyU5zuE3Gnf6w2uCufVQdlmpXY0nl4wV3WOCD6iil7xgT0mH5tDpgLWecyfaw2q76CF4P6HOOkBJahzgGD-gTXM-Dzi54FCxaw1SwKewIIeV7fDF7c8-vbIaIdAFmzoCu7nb957dTSHME5Dz65kpLrD9sQw7oox6Ku87pWfXE6iHB8-U9rr5enH85W9eXV-_en60ua9O0JNdSCkkto1bSpueCyg3RhLcba7gUljVEA5Rab1rgcqN72VnMOkpJRxrdi54dV2_3vtO8GaE34HPUg5qiG3XcqqCd-pfx7kZdh19KllsJQYrBq71B2dypcu0M5sYE78FkRaSgnLZF9Hr5JYafM6SsRpcMDIP2EOakaCcwZZw3O-nJXmpiSCmCfZiFYLULVe1DVUuopeHl3xs8yP-kWARvlgnn6X9mvwGnmrBG</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>2680237745</pqid></control><display><type>article</type><title>Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats</title><source>Oxford University Press Journals All Titles (1996-Current)</source><source>MEDLINE</source><source>Alma/SFX Local Collection</source><source>Free Full-Text Journals in Chemistry</source><creator>Jackson, Thomas W ; Henriquez, Andres R ; Snow, Samantha J ; Schladweiler, Mette C ; Fisher, Anna A ; Alewel, Devin I ; House, John S ; Kodavanti, Urmila P</creator><creatorcontrib>Jackson, Thomas W ; Henriquez, Andres R ; Snow, Samantha J ; Schladweiler, Mette C ; Fisher, Anna A ; Alewel, Devin I ; House, John S ; Kodavanti, Urmila P ; Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</creatorcontrib><description>Abstract
Ozone-induced lung injury, inflammation, and pulmonary/hypothalamus gene expression changes are diminished in adrenalectomized (AD) 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 AD rats, these changes would be diminished. In total, 5–7 days after sham (SH) or AD surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4 h. 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 SH but not AD rats. Ozone-induced inhibition of glucose-mediated insulin release was absent in AD rats. Unlike diminution of ozone-induced hypothalamus and lung mRNA expression changes, AD in air-exposed rats (AD-air/SH-air) caused differential hepatic expression of ∼1000 genes. Likewise, ozone in AD rats caused differential expression of ∼1000 genes (AD-ozone/AD-air). Ozone-induced hepatic changes in SH rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified similarity to responses produced by glucocorticoids and pathways involving forskolin. These changes were absent in AD rats exposed to ozone. However, ozone caused unique changes in AD 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 likely involved in glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and necessitate further research elucidating their role in propagating environmentally driven diseases.</description><identifier>ISSN: 1096-6080</identifier><identifier>ISSN: 1096-0929</identifier><identifier>EISSN: 1096-0929</identifier><identifier>DOI: 10.1093/toxsci/kfac065</identifier><identifier>PMID: 35737395</identifier><language>eng</language><publisher>United States: Oxford University Press</publisher><subject>Animals ; Computational Toxicology and Databases ; Corticosterone ; Homeostasis ; Insulin ; Male ; Ozone - toxicity ; Rats ; Rats, Inbred WKY ; RNA, Messenger ; Toxicology</subject><ispartof>Toxicological sciences, 2022-08, Vol.189 (1), p.73-90</ispartof><rights>Published by Oxford University Press on behalf of the Society of Toxicology 2022. 2022</rights><rights>Published by Oxford University Press on behalf of the Society of Toxicology 2022.</rights><rights>Published by Oxford University Press on behalf of the Society of Toxicology 2022. 2022</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c451t-99892f32f924d7829b1a175bfc798f341aee9b1dc5e79bad96f036221614ad8d3</citedby><cites>FETCH-LOGICAL-c451t-99892f32f924d7829b1a175bfc798f341aee9b1dc5e79bad96f036221614ad8d3</cites><orcidid>0000-0002-7996-0412 ; 0000-0002-8447-7871 ; 0000-0001-6333-1024 ; 0000000279960412 ; 0000000284477871 ; 0000000163331024</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,314,776,780,881,1578,27901,27902</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/35737395$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink><backlink>$$Uhttps://www.osti.gov/biblio/1982725$$D View this record in Osti.gov$$Hfree_for_read</backlink></links><search><creatorcontrib>Jackson, Thomas W</creatorcontrib><creatorcontrib>Henriquez, Andres R</creatorcontrib><creatorcontrib>Snow, Samantha J</creatorcontrib><creatorcontrib>Schladweiler, Mette C</creatorcontrib><creatorcontrib>Fisher, Anna A</creatorcontrib><creatorcontrib>Alewel, Devin I</creatorcontrib><creatorcontrib>House, John S</creatorcontrib><creatorcontrib>Kodavanti, Urmila P</creatorcontrib><creatorcontrib>Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</creatorcontrib><title>Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats</title><title>Toxicological sciences</title><addtitle>Toxicol Sci</addtitle><description>Abstract
Ozone-induced lung injury, inflammation, and pulmonary/hypothalamus gene expression changes are diminished in adrenalectomized (AD) 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 AD rats, these changes would be diminished. In total, 5–7 days after sham (SH) or AD surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4 h. 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 SH but not AD rats. Ozone-induced inhibition of glucose-mediated insulin release was absent in AD rats. Unlike diminution of ozone-induced hypothalamus and lung mRNA expression changes, AD in air-exposed rats (AD-air/SH-air) caused differential hepatic expression of ∼1000 genes. Likewise, ozone in AD rats caused differential expression of ∼1000 genes (AD-ozone/AD-air). Ozone-induced hepatic changes in SH rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified similarity to responses produced by glucocorticoids and pathways involving forskolin. These changes were absent in AD rats exposed to ozone. However, ozone caused unique changes in AD 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 likely involved in glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and necessitate further research elucidating their role in propagating environmentally driven diseases.</description><subject>Animals</subject><subject>Computational Toxicology and Databases</subject><subject>Corticosterone</subject><subject>Homeostasis</subject><subject>Insulin</subject><subject>Male</subject><subject>Ozone - toxicity</subject><subject>Rats</subject><subject>Rats, Inbred WKY</subject><subject>RNA, Messenger</subject><subject>Toxicology</subject><issn>1096-6080</issn><issn>1096-0929</issn><issn>1096-0929</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2022</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFUU1v1DAQjRCIfsCVI7I4wSGtP5LYviCtqpZFFFXiQxwtrzNuDYkdbAd1--vxdkMFJ05-mvfmeWZeVb0g-IRgyU5zuE3Gnf6w2uCufVQdlmpXY0nl4wV3WOCD6iil7xgT0mH5tDpgLWecyfaw2q76CF4P6HOOkBJahzgGD-gTXM-Dzi54FCxaw1SwKewIIeV7fDF7c8-vbIaIdAFmzoCu7nb957dTSHME5Dz65kpLrD9sQw7oox6Ku87pWfXE6iHB8-U9rr5enH85W9eXV-_en60ua9O0JNdSCkkto1bSpueCyg3RhLcba7gUljVEA5Rab1rgcqN72VnMOkpJRxrdi54dV2_3vtO8GaE34HPUg5qiG3XcqqCd-pfx7kZdh19KllsJQYrBq71B2dypcu0M5sYE78FkRaSgnLZF9Hr5JYafM6SsRpcMDIP2EOakaCcwZZw3O-nJXmpiSCmCfZiFYLULVe1DVUuopeHl3xs8yP-kWARvlgnn6X9mvwGnmrBG</recordid><startdate>20220825</startdate><enddate>20220825</enddate><creator>Jackson, Thomas W</creator><creator>Henriquez, Andres R</creator><creator>Snow, Samantha J</creator><creator>Schladweiler, Mette C</creator><creator>Fisher, Anna A</creator><creator>Alewel, Devin I</creator><creator>House, John S</creator><creator>Kodavanti, Urmila P</creator><general>Oxford University Press</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>OTOTI</scope><scope>5PM</scope><orcidid>https://orcid.org/0000-0002-7996-0412</orcidid><orcidid>https://orcid.org/0000-0002-8447-7871</orcidid><orcidid>https://orcid.org/0000-0001-6333-1024</orcidid><orcidid>https://orcid.org/0000000279960412</orcidid><orcidid>https://orcid.org/0000000284477871</orcidid><orcidid>https://orcid.org/0000000163331024</orcidid></search><sort><creationdate>20220825</creationdate><title>Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats</title><author>Jackson, Thomas W ; Henriquez, Andres R ; Snow, Samantha J ; Schladweiler, Mette C ; Fisher, Anna A ; Alewel, Devin I ; House, John S ; Kodavanti, Urmila P</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c451t-99892f32f924d7829b1a175bfc798f341aee9b1dc5e79bad96f036221614ad8d3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2022</creationdate><topic>Animals</topic><topic>Computational Toxicology and Databases</topic><topic>Corticosterone</topic><topic>Homeostasis</topic><topic>Insulin</topic><topic>Male</topic><topic>Ozone - toxicity</topic><topic>Rats</topic><topic>Rats, Inbred WKY</topic><topic>RNA, Messenger</topic><topic>Toxicology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Jackson, Thomas W</creatorcontrib><creatorcontrib>Henriquez, Andres R</creatorcontrib><creatorcontrib>Snow, Samantha J</creatorcontrib><creatorcontrib>Schladweiler, Mette C</creatorcontrib><creatorcontrib>Fisher, Anna A</creatorcontrib><creatorcontrib>Alewel, Devin I</creatorcontrib><creatorcontrib>House, John S</creatorcontrib><creatorcontrib>Kodavanti, Urmila P</creatorcontrib><creatorcontrib>Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>OSTI.GOV</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Toxicological sciences</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Jackson, Thomas W</au><au>Henriquez, Andres R</au><au>Snow, Samantha J</au><au>Schladweiler, Mette C</au><au>Fisher, Anna A</au><au>Alewel, Devin I</au><au>House, John S</au><au>Kodavanti, Urmila P</au><aucorp>Oak Ridge Institute for Science and Education (ORISE), Oak Ridge, TN (United States)</aucorp><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats</atitle><jtitle>Toxicological sciences</jtitle><addtitle>Toxicol Sci</addtitle><date>2022-08-25</date><risdate>2022</risdate><volume>189</volume><issue>1</issue><spage>73</spage><epage>90</epage><pages>73-90</pages><issn>1096-6080</issn><issn>1096-0929</issn><eissn>1096-0929</eissn><abstract>Abstract
Ozone-induced lung injury, inflammation, and pulmonary/hypothalamus gene expression changes are diminished in adrenalectomized (AD) 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 AD rats, these changes would be diminished. In total, 5–7 days after sham (SH) or AD surgeries, male Wistar-Kyoto rats were exposed to air or 0.8-ppm ozone for 4 h. 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 SH but not AD rats. Ozone-induced inhibition of glucose-mediated insulin release was absent in AD rats. Unlike diminution of ozone-induced hypothalamus and lung mRNA expression changes, AD in air-exposed rats (AD-air/SH-air) caused differential hepatic expression of ∼1000 genes. Likewise, ozone in AD rats caused differential expression of ∼1000 genes (AD-ozone/AD-air). Ozone-induced hepatic changes in SH rats reflected enrichment for pathways involving metabolic processes, including acetyl-CoA biosynthesis, TCA cycle, and sirtuins. Upstream predictor analysis identified similarity to responses produced by glucocorticoids and pathways involving forskolin. These changes were absent in AD rats exposed to ozone. However, ozone caused unique changes in AD 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 likely involved in glucocorticoid insufficiency. These data demonstrate the critical role of adrenal stress hormones in ozone-induced hepatic homeostasis and necessitate further research elucidating their role in propagating environmentally driven diseases.</abstract><cop>United States</cop><pub>Oxford University Press</pub><pmid>35737395</pmid><doi>10.1093/toxsci/kfac065</doi><tpages>18</tpages><orcidid>https://orcid.org/0000-0002-7996-0412</orcidid><orcidid>https://orcid.org/0000-0002-8447-7871</orcidid><orcidid>https://orcid.org/0000-0001-6333-1024</orcidid><orcidid>https://orcid.org/0000000279960412</orcidid><orcidid>https://orcid.org/0000000284477871</orcidid><orcidid>https://orcid.org/0000000163331024</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1096-6080 |
| ispartof | Toxicological sciences, 2022-08, Vol.189 (1), p.73-90 |
| issn | 1096-6080 1096-0929 1096-0929 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_9609881 |
| source | Oxford University Press Journals All Titles (1996-Current); MEDLINE; Alma/SFX Local Collection; Free Full-Text Journals in Chemistry |
| subjects | Animals Computational Toxicology and Databases Corticosterone Homeostasis Insulin Male Ozone - toxicity Rats Rats, Inbred WKY RNA, Messenger Toxicology |
| title | Adrenal Stress Hormone Regulation of Hepatic Homeostatic Function After an Acute Ozone Exposure in Wistar-Kyoto Male Rats |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-02-09T02%3A39%3A01IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Adrenal%20Stress%20Hormone%20Regulation%20of%20Hepatic%20Homeostatic%20Function%20After%20an%20Acute%20Ozone%20Exposure%20in%20Wistar-Kyoto%20Male%20Rats&rft.jtitle=Toxicological%20sciences&rft.au=Jackson,%20Thomas%20W&rft.aucorp=Oak%20Ridge%20Institute%20for%20Science%20and%20Education%20(ORISE),%20Oak%20Ridge,%20TN%20(United%20States)&rft.date=2022-08-25&rft.volume=189&rft.issue=1&rft.spage=73&rft.epage=90&rft.pages=73-90&rft.issn=1096-6080&rft.eissn=1096-0929&rft_id=info:doi/10.1093/toxsci/kfac065&rft_dat=%3Cproquest_pubme%3E2680237745%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=2680237745&rft_id=info:pmid/35737395&rft_oup_id=10.1093/toxsci/kfac065&rfr_iscdi=true |