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The fructose transporter GLUT5 (SLC2A5) is required for intestinal fructose absorption. GLUT5 expression is induced in the intestine and skeletal muscle of type 2 diabetes (T2D) patients and in certain cancers that are dependent on fructose metabolism, indicating that modulation of GLUT5 levels could have potential in the treatment of these diseases. Using an unbiased screen for transcriptional control of the human <jats:italic>GLUT5<\/jats:italic> promoter we identified a strong and specific regulation by liver X receptor \u03b1 (LXR\u03b1, NR1H3). Using promoter truncations and site-directed mutagenesis we identified a functional LXR response element (LXRE) in the human <jats:italic>GLUT5<\/jats:italic> promoter, located at \u2212385 bp relative to the transcriptional start site (TSS). Finally, mice treated with LXR agonist T0901317 showed an increase in Glut5 mRNA and protein levels in duodenum and adipose tissue, underscoring the <jats:italic>in vivo<\/jats:italic> relevance of its regulation by LXR. Together, our findings show that LXR\u03b1 regulates GLUT5 in mice and humans. As a ligand-activated transcription factor, LXR\u03b1 might provide novel pharmacologic strategies for the selective modulation of GLUT5 activity in the treatment of metabolic disease as well as cancer.<\/jats:p>","DOI":"10.1038\/s41598-019-45803-x","type":"journal-article","created":{"date-parts":[[2019,6,26]],"date-time":"2019-06-26T10:02:56Z","timestamp":1561543376000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":50,"title":["Identification of the fructose transporter GLUT5 (SLC2A5) as a novel target of nuclear receptor LXR"],"prefix":"10.1038","volume":"9","author":[{"given":"Irene","family":"Zwarts","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tim","family":"van Zutphen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janine K.","family":"Kruit","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weilin","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maaike H.","family":"Oosterveer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henkjan J.","family":"Verkade","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4220-4779","authenticated-orcid":false,"given":"N. 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