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Dietary fructose is predominantly transported into cells through the solute carrier family 2 member 5 and\/or member 2, and then metabolized by fructokinase (also known as ketohexokinase, KHK), which is primarily expressed in the intestine, liver, and kidney. The significant contribution of KHK\u2010mediated fructose metabolism in the intestine or liver to sugar\u2010induced metabolic syndrome has been well documented. This study aimed to elucidate the pathophysiological significance of renal KHK\u2010mediated fructose metabolism in the pathogenesis of fructose\u2010induced metabolic syndrome.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      A mouse model with inducible deletion of both KHK isoforms (KHK\u2010A and KHK\u2010C) in renal tubules was generated using the\n                      <jats:italic>Cre\u2010LoxP<\/jats:italic>\n                      recombination system. We then systematically evaluated parameters associated with fructose\u2010induced metabolic syndrome in these mice fed a 20% fructose solution (w\/v).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      In mice receiving excess fructose solutions, the inducible deletion of KHK via the Pax8\u2010rtTA\/LC1 system entirely blocks fructose metabolism and is sufficient to prevent the development of metabolic syndrome. The latter is evidenced by improved glucose and insulin resistance, alleviated hepatic steatosis and liver injury, mitigated adipose tissue remodeling, and strengthened colonic epithelial barrier integrity in fructose\u2010fed\n                      <jats:italic>Khk<\/jats:italic>\n                      \u2010deficient mice. These protections are likely attributed to the reduced uric acid generation resulting from the blockade of fructose metabolism.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Our findings suggest that KHK\u2010mediated fructose metabolism in the kidneys may be crucial for the development of fructose\u2010induced metabolic syndrome.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/apha.70187","type":"journal-article","created":{"date-parts":[[2026,3,8]],"date-time":"2026-03-08T16:51:25Z","timestamp":1772988685000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":5,"title":["Pax8\u2010\n                    <scp>rtTA<\/scp>\n                    \/\n                    <scp>LC1<\/scp>\n                    \u2010Driven Inducible Ketohexokinase Deletion Protects Against High Fructose\u2010Induced Metabolic Syndrome in Mice"],"prefix":"10.1111","volume":"242","author":[{"given":"Xiaoli","family":"Yi","sequence":"first","affiliation":[{"name":"Translational Medicine Centre Jiangxi University of Chinese Medicine  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ying","family":"Zhu","sequence":"additional","affiliation":[{"name":"Translational Medicine Centre Jiangxi University of Chinese Medicine  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mulan","family":"Wang","sequence":"additional","affiliation":[{"name":"Translational Medicine Centre Jiangxi University of Chinese Medicine  Nanchang China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shanshan","family":"Song","sequence":"additional","affiliation":[{"name":"Translational Medicine Centre Jiangxi University of Chinese Medicine  Nanchang 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