{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,14]],"date-time":"2026-05-14T21:19:12Z","timestamp":1778793552443,"version":"3.51.4"},"reference-count":25,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2025,11,12]],"date-time":"2025-11-12T00:00:00Z","timestamp":1762905600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82170583"],"award-info":[{"award-number":["82170583"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["febs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FEBS Journal"],"published-print":{"date-parts":[[2026,3]]},"abstract":"<jats:p>\n                    Excessive dietary fructose consumption is a significant contributor to the development of metabolic dysfunction\u2010associated steatotic liver disease (MASLD). However, the role of the intestinal fructose transporter, glucose transporter 5 (GLUT5), in this process remains poorly understood. This study aimed to investigate the potential use of GLUT5 as a novel therapeutic target for MASLD. Eight\u2010week\u2010old male C57BL\/6J wild\u2010type (WT) mice were fed a high\u2010fat diet (HFD) or a high\u2010fat diet supplemented with 10% or 25% fructose in drinking water (HFF) for 8\u2009weeks to investigate the effects of high\u2010fructose intake on MASLD development. To further elucidate the role of GLUT5, we utilized an intestine\u2010specific GLUT5 knockout (\n                    <jats:italic>Slc2a5<\/jats:italic>\n                    \u2010IKO) mouse model with HFF diet intervention to evaluate the protective effects of GLUT5 inhibition against high\u2010fructose\u2010induced liver injury. Additionally, the GLUT5 transporter inhibitor, 2,5\u2010anhydro\u2010D\u2010mannitol (2,5\u2010AM), was administered to HFF\u2010fed WT mice to validate the alleviating effect on MASLD. The intestinal expression of GLUT5, liver and intestinal histology, and serum biochemical parameters were analyzed. Intestinal GLUT5 expression was significantly upregulated in WT mice fed HFF for 8\u2009weeks, which developed impaired liver function and metabolic abnormalities. Compared with WT mice, liver damage was significantly attenuated in\n                    <jats:italic>Slc2a5<\/jats:italic>\n                    \u2010IKO mice with the\u20098\u2010week HFF diet plan. Furthermore, we demonstrated that the GLUT5 inhibitor, 2,5\u2010AM, effectively suppressed intestinal GLUT5 expression and ameliorated the progression of MASLD in WT mice. Intestinal GLUT5 represents a potential therapeutic target for mitigating high\u2010fructose\u2010induced MASLD.\n                  <\/jats:p>","DOI":"10.1111\/febs.70338","type":"journal-article","created":{"date-parts":[[2025,11,13]],"date-time":"2025-11-13T03:45:16Z","timestamp":1763005516000},"page":"1545-1555","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Targeting intestinal transporter\n                    <scp>GLUT5<\/scp>\n                    to alleviate the high\u2010fructose\u2010induced steatotic liver disease"],"prefix":"10.1111","volume":"293","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8811-1455","authenticated-orcid":false,"given":"Huiying","family":"Wang","sequence":"first","affiliation":[{"name":"Children's Hospital, Zhejiang University School of Medicine, National Clinical Research Center for Child Health  Hangzhou 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