{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,17]],"date-time":"2026-07-17T00:06:55Z","timestamp":1784246815560,"version":"3.55.0"},"reference-count":37,"publisher":"Oxford University Press (OUP)","license":[{"start":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T00:00:00Z","timestamp":1782518400000},"content-version":"am","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82300781"],"award-info":[{"award-number":["82300781"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82570807"],"award-info":[{"award-number":["82570807"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["U25A2033"],"award-info":[{"award-number":["U25A2033"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>The ketogenic diet (KD) is widely used in disease management and healthy populations, but its long-term physiological safety remains unclear. While KD protects against kidney injury in models, its effects on healthy renal tissue are poorly understood.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>Two-sample Mendelian randomization (MR) analysed causality between serum 3-hydroxybutyrate (BHB) and renal injury. Mice underwent 3-month KD, short-term BHB gavage or time-restricted feeding (tRF). Renal histology, fibrosis and partial epithelial\u2013mesenchymal transition (pEMT) were assessed. RNA sequencing identified pathways, validated in HK-2 cells.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>Genetically elevated serum BHB was causally linked to higher renal injury risk. In healthy mice, long-term KD-induced renal interstitial fibrosis and maladaptive repair of renal tubular epithelial cells (TECs), characterized by partial EMT, while short-term BHB gavage or tRF reproduced early pro-fibrotic changes (partial EMT and increased fibronectin (FN)\/collagen I (Col1) expression) without establishing overt fibrosis. In contrast, in mice with unilateral ischemia-reperfusion injury (UIRI), both BHB and tRF reduced renal damage, renal interstitial collagen deposition and maladaptive repair of TECs. Mechanically, KD up-regulated Wnt8b and Junb in healthy kidneys, and BHB treatment promoted \u03b2-catenin nuclear translocation in a Wnt8b-dependent manner. Knockdown of Wnt8b or Junb suppressed BHB-induced partial EMT in HK-2 cells. Notably, BHB oppositely regulated Wnt8b in injured kidneys, where it attenuated injury-driven Wnt8b elevation.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Ketosis exhibits a dichotomous renal role: promoting fibrosis through Wnt8b\/Junb mediated partial EMT in healthy tissue, while protecting against injury-induced fibrosis. These findings emphasize the context-dependence of KD and caution against its long-term use in healthy individuals.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/qjmed\/hcag166","type":"journal-article","created":{"date-parts":[[2026,6,29]],"date-time":"2026-06-29T06:06:49Z","timestamp":1782713209000},"source":"Crossref","is-referenced-by-count":0,"title":["Ketogenic diet promotes renal fibrosis in healthy tissue via Wnt8b and Junb, while protecting against injury-induced fibrosis"],"prefix":"10.1093","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3682-1578","authenticated-orcid":false,"given":"Yuzhan","family":"Zhang","sequence":"first","affiliation":[{"name":"Department of Nephrology, Xijing Hospital, Air Force Military Medical University , Xian, Shaanxi,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Guan","sequence":"additional","affiliation":[{"name":"Department of Nephrology, Xijing Hospital, Air Force Military 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