{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,27]],"date-time":"2026-05-27T18:49:51Z","timestamp":1779907791751,"version":"3.53.1"},"reference-count":51,"publisher":"Oxford University Press (OUP)","issue":"2","funder":[{"DOI":"10.13039\/100000139","name":"U.S. Environmental Protection Agency","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000139","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Intramural Research Program"},{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["IIE-15120279"],"award-info":[{"award-number":["IIE-15120279"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"U.S. Environmental Protection Agency-University of North Carolina"},{"name":"Center for Environmental Medicine"},{"name":"Asthma and Lung Biology Cooperative Agreement","award":["CR-83515201"],"award-info":[{"award-number":["CR-83515201"]}]},{"name":"U.S. Environmental Protection Agency-Oak Ridge Institute for Science and Education Cooperative Agreement","award":["161550"],"award-info":[{"award-number":["161550"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2021,5,27]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Air pollution has been associated with metabolic diseases and hepatic steatosis-like changes. We have shown that ozone alters liver gene expression for metabolic processes through neuroendocrine activation. This study aimed to further characterize ozone-induced changes and to determine the impact of hepatic vagotomy (HV) which reduces parasympathetic influence. Twelve-week-old male Wistar-Kyoto rats underwent HV or sham surgery 5\u20136 days before air or ozone exposure (0 or 1\u2009ppm; 4\u2009h\/day for 1 or 2 days). Ozone-induced lung injury, hyperglycemia, glucose intolerance, and increases in circulating cholesterol, triglycerides, and leptin were similar in rats with HV and sham surgery. However, decreases in circulating insulin and increased HDL and LDL were observed only in ozone-exposed HV rats. Ozone exposure resulted in changed liver gene expression in both sham and HV rats (sham &amp;gt; HV), however, HV did not change expression in air-exposed rats. Upstream target analysis revealed that ozone-induced transcriptomic changes were similar to responses induced by glucocorticoid-mediated processes in both sham and HV rats. The directionality of ozone-induced changes reflecting cellular response to stress, metabolic pathways, and immune surveillance was similar in sham and HV rats. However, pathways regulating cell-cycle, regeneration, proliferation, cell growth, and survival were enriched by ozone in a directionally opposing manner between sham and HV rats. In conclusion, parasympathetic innervation modulated ozone-induced liver transcriptional responses for cell growth and regeneration without affecting stress-mediated metabolic changes. Thus, impaired neuroendocrine axes and parasympathetic innervation could collectively contribute to adverse effects of air pollutants on the liver.<\/jats:p>","DOI":"10.1093\/toxsci\/kfab025","type":"journal-article","created":{"date-parts":[[2021,2,25]],"date-time":"2021-02-25T17:45:41Z","timestamp":1614275141000},"page":"229-245","source":"Crossref","is-referenced-by-count":12,"title":["The Role of Hepatic Vagal Tone in Ozone-Induced Metabolic Dysfunction in the Liver"],"prefix":"10.1093","volume":"181","author":[{"given":"Catherine H","family":"Colonna","sequence":"first","affiliation":[{"name":"Oak Ridge Institute for Science and Education Research Participation Program, U.S. Environmental Protection Agency, Research Triangle Park, North Carolina, 27711"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andres R","family":"Henriquez","sequence":"additional","affiliation":[{"name":"Oak Ridge Institute for Science and Education Research Participation Program, U.S. 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