{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,24]],"date-time":"2026-08-24T17:08:26Z","timestamp":1787591306325,"version":"build-2736575974"},"reference-count":71,"publisher":"MDPI AG","issue":"10","license":[{"start":{"date-parts":[[2023,10,1]],"date-time":"2023-10-01T00:00:00Z","timestamp":1696118400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000066","name":"UNC Superfund Research program","doi-asserted-by":"publisher","award":["P42ES031007"],"award-info":[{"award-number":["P42ES031007"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"UNC Superfund Research program","doi-asserted-by":"publisher","award":["P30ES010126"],"award-info":[{"award-number":["P30ES010126"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"University of North Carolina Center for Environmental Health and Susceptibility","doi-asserted-by":"publisher","award":["P42ES031007"],"award-info":[{"award-number":["P42ES031007"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000066","name":"University of North Carolina Center for Environmental Health and Susceptibility","doi-asserted-by":"publisher","award":["P30ES010126"],"award-info":[{"award-number":["P30ES010126"]}],"id":[{"id":"10.13039\/100000066","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Toxics"],"abstract":"<jats:p>Inorganic arsenic in drinking water is prioritized as a top environmental contaminant by the World Health Organization, with over 230 million people potentially being exposed. Arsenic toxicity has been well documented and is associated with a plethora of human diseases, including diabetes, as established in numerous animal and epidemiological studies. Our previous study revealed that arsenic exposure leads to the inhibition of nuclear receptors, including LXR\/RXR. To this end, FXR is a nuclear receptor central to glucose and lipid metabolism. However, limited studies are available for understanding arsenic exposure-FXR interactions. Herein, we report that FXR knockout mice developed more profound glucose intolerance than wild-type mice upon arsenic exposure, supporting the regulatory role of FXR in arsenic-induced glucose intolerance. We further exposed mice to arsenic and tested if GW4064, a FXR agonist, could improve glucose intolerance and dysregulation of hepatic proteins and serum metabolites. Our data showed arsenic-induced glucose intolerance was remarkably diminished by GW4064, accompanied by a significant ratio of alleviation of dysregulation in hepatic proteins (83%) and annotated serum metabolites (58%). In particular, hepatic proteins \u201crescued\u201d from arsenic toxicity by GW4064 featured members of glucose and lipid utilization. For instance, the expression of PCK1, a candidate gene for diabetes and obesity that facilitates gluconeogenesis, was repressed under arsenic exposure in the liver, but revived with the GW4064 supplement. Together, our comprehensive dataset indicates FXR plays a key role and may serve as a potential therapeutic for arsenic-induced metabolic disorders.<\/jats:p>","DOI":"10.3390\/toxics11100833","type":"journal-article","created":{"date-parts":[[2023,10,2]],"date-time":"2023-10-02T04:39:30Z","timestamp":1696221570000},"page":"833","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["The Role of the Nuclear Receptor FXR in Arsenic-Induced Glucose Intolerance in Mice"],"prefix":"10.3390","volume":"11","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-7134-3623","authenticated-orcid":false,"given":"Yifei","family":"Yang","sequence":"first","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1189-6511","authenticated-orcid":false,"given":"Yun-Chung","family":"Hsiao","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chih-Wei","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun","family":"Lu","sequence":"additional","affiliation":[{"name":"Department of Environmental Sciences and Engineering, University of North Carolina, Chapel Hill, NC 27599, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,10,1]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"101079","DOI":"10.1016\/j.gsf.2020.08.015","article-title":"Arsenic contamination of groundwater: A global synopsis with focus on the Indian Peninsula","volume":"12","author":"Shaji","year":"2021","journal-title":"Geosci. 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