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Thiamine Transporter 2 (THTR2) encoded by SLC19A3 plays an ill-defined role in the maintenance of tissue thiamine, thiamine monophosphate, and thiamine diphosphate (TDP) levels. To evaluate the impact of THTR2 on tissue thiamine status and metabolism, we expressed the human SLC19A3 transgene in the intestine of total body Slc19a3 knockout (KO) mice. Male and female wildtype (WT) and transgenic (TG) mice were fed either 17 mg\/kg (1\u00d7) or 85 mg\/kg (5\u00d7) thiamine hydrochloride diet, while KOs were only fed the 5\u00d7 diet. Thiamine vitamers in plasma, red blood cells, duodenum, brain, liver, kidney, heart, and adipose tissue were measured. Untargeted metabolomics were performed on the brain tissues of groups with equivalent plasma thiamine. KO mice had ~two- and ~three-fold lower plasma and brain thiamine levels than WT on the 5\u00d7 diet. Circulating vitamers were sensitive to diet and equivalent in TG and WT mice. However, TG had 60% lower thiamine but normal brain TDP levels regardless of diet, with subtle differences in the heart and liver. The loss of THTR2 reduced levels of nucleic acid and amino acid derivatives in the brain. Therefore, mutation or inhibition of THTR2 may alter the brain metabolome and reduce the thiamine reservoir for TDP biosynthesis.<\/jats:p>","DOI":"10.3390\/metabo13080885","type":"journal-article","created":{"date-parts":[[2023,7,27]],"date-time":"2023-07-27T02:14:48Z","timestamp":1690424088000},"page":"885","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["The Impacts of Slc19a3 Deletion and Intestinal SLC19A3 Insertion on Thiamine Distribution and Brain Metabolism in the Mouse"],"prefix":"10.3390","volume":"13","author":[{"given":"Anita","family":"Wen","sequence":"first","affiliation":[{"name":"Department of Nutrition, University of California, Davis, CA 95616, USA"},{"name":"West Coast Metabolomics Center, Genome Center, University of California, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Gerald J. and Dorothy R. Friedman School of Nutrition Science & Policy, Tufts University, Boston, MA 02111, USA"},{"name":"Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8121-8746","authenticated-orcid":false,"given":"Sook Wah","family":"Yee","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brian I.","family":"Park","sequence":"additional","affiliation":[{"name":"Gerald J. and Dorothy R. Friedman School of Nutrition Science & Policy, Tufts University, Boston, MA 02111, USA"},{"name":"Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kathleen M.","family":"Giacomini","sequence":"additional","affiliation":[{"name":"Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA 92521, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5062-387X","authenticated-orcid":false,"given":"Andrew S.","family":"Greenberg","sequence":"additional","affiliation":[{"name":"Gerald J. and Dorothy R. Friedman School of Nutrition Science & Policy, Tufts University, Boston, MA 02111, USA"},{"name":"Jean Mayer USDA Human Nutrition Research Center on Aging, Tufts University, Boston, MA 02111, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9632-6571","authenticated-orcid":false,"given":"John W.","family":"Newman","sequence":"additional","affiliation":[{"name":"Department of Nutrition, University of California, Davis, CA 95616, USA"},{"name":"West Coast Metabolomics Center, Genome Center, University of California, Davis, CA 95616, USA"},{"name":"USDA Western Human Nutrition Research Center, Davis, CA 95616, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2023,7,26]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/nyas.13919","article-title":"Thiamine deficiency disorders: Diagnosis, prevalence, and a roadmap for global control programs","volume":"1430","author":"Whitfield","year":"2018","journal-title":"Ann. 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