{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T12:36:52Z","timestamp":1790685412336,"version":"4.1.0"},"reference-count":53,"publisher":"Public Library of Science (PLoS)","issue":"12","license":[{"start":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T00:00:00Z","timestamp":1607990400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"National Institute of Environmental Health Sciences","doi-asserted-by":"publisher","award":["ES-027488"],"award-info":[{"award-number":["ES-027488"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Winston Foundation"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>Activation of the aryl hydrocarbon receptor (AHR) by the environmental toxin dioxin (2,3,7,8-tetrachlorodibenzo-<jats:italic>p<\/jats:italic>-dioxin, TCDD) causes diverse toxicities, including thymus atrophy and hepatosteatosis. The mechanisms by which AHR activation by TCDD leads to these toxicities are not fully understood. Here we studied the effects of TCDD on a major energy pathway, glycolysis, using the chick embryo close to hatching, a well-established model for studying dioxin toxicity. We showed that 24 hr of TCDD treatment causes changes in glycolysis in both thymus and liver. In thymus glands, TCDD decreased mRNAs for glycolytic genes and glucose transporters, glycolytic indices and levels of<jats:italic>IL7<\/jats:italic>mRNA, phosphorylated AKT (pAKT) and HIF1A, stimulators of glycolysis and promoters of survival and proliferation of thymic lymphocytes. In contrast, in liver, TCDD increased mRNA levels for glycolytic genes and glucose transporters, glycolytic endpoints and pAKT levels. Similarly, increases by TCDD in mRNA levels for glycolytic genes and glucose transporters in human primary hepatocytes showed that effects in chick embryo liver pertain also to human cells. Treatment with the glycolytic inhibitor 2-deoxy-d-glucose exacerbated the effects on thymus atrophy by TCDD, supporting a role for decreased glycolysis in thymus atrophy by TCDD, but did not prevent hepatosteatosis. NAD<jats:sup>+<\/jats:sup>precursors abolished TCDD effects on glycolytic endpoints in both thymus and liver. In summary, we report here that dioxin disrupts glycolysis mediated energy metabolism in both thymus and liver, and that it does so in opposite ways, decreasing it in the thymus and increasing it in the liver. Further, the findings support NAD<jats:sup>+<\/jats:sup>boosting as a strategy against metabolic effects of environmental pollutants such as dioxins.<\/jats:p>","DOI":"10.1371\/journal.pone.0243842","type":"journal-article","created":{"date-parts":[[2020,12,15]],"date-time":"2020-12-15T19:10:01Z","timestamp":1608059401000},"page":"e0243842","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":11,"title":["Organ-specific effects on glycolysis by the dioxin-activated aryl hydrocarbon receptor"],"prefix":"10.1371","volume":"15","author":[{"given":"Silvia","family":"Diani-Moore","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tiago","family":"Marques Pedro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7422-1146","authenticated-orcid":true,"given":"Arleen 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