{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,30]],"date-time":"2026-07-30T16:57:29Z","timestamp":1785430649401,"version":"3.56.0"},"reference-count":26,"publisher":"MDPI AG","issue":"13","license":[{"start":{"date-parts":[[2026,7,4]],"date-time":"2026-07-04T00:00:00Z","timestamp":1783123200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82070749"],"award-info":[{"award-number":["82070749"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82070749"],"award-info":[{"award-number":["82070749"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National High-Level Hospital Clinical Research Funding","award":["2022CX13"],"award-info":[{"award-number":["2022CX13"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The rising burden of diabetic kidney disease (DKD) and its associated lipid abnormalities underscores the need for new mechanistic insights. Uromodulin, a kidney-enriched protein, has been associated with metabolic disorders in human studies, yet its functional role in systemic lipid metabolism remains elusive. In this study, transcriptomic datasets were analyzed to investigate uromodulin expression and biological function in DKD. Subsequently, a diabetic model was induced in UMOD+\/+ and UMOD\u2212\/\u2212 rats using a combination of a high-fat diet, unilateral nephrectomy, and streptozotocin to assess renal and metabolic phenotypes. Public RNA-seq data indicated that uromodulin expression was downregulated in DKD and was enriched in the fatty acid metabolism pathway. At baseline, UMOD\u2212\/\u2212 rats resembled UMOD+\/+ rats in terms of growth, routine serum lipids, and major organ function. However, in diabetes, UMOD\u2212\/\u2212 rats exhibited higher mortality and pronounced hyperlipidemia. Hyperlipidemia occurred prior to the onset of renal dysfunction. Of note, this exacerbated lipid dysregulation represented a lipodystrophy-like phenotype rather than secondary changes in the pancreas, liver, or circulating cytokines (IL-6, IL-1\u03b2, and TNF-\u03b1). Moreover, UMOD\u2212\/\u2212 rats displayed exacerbated tubular injury and enhanced renal lipid accumulation in DKD relative to UMOD+\/+ rats. Collectively, uromodulin protects diabetic rats from death, prevents epididymal white adipose tissue from browning, and attenuates kidney injury. Our findings identify uromodulin as a novel regulator of the kidney\u2013adipose axis.<\/jats:p>","DOI":"10.3390\/ijms27136009","type":"journal-article","created":{"date-parts":[[2026,7,6]],"date-time":"2026-07-06T13:43:14Z","timestamp":1783345394000},"page":"6009","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Uromodulin: A Novel Regulator of the Kidney\u2013Adipose Axis in Diabetic Kidney Disease"],"prefix":"10.3390","volume":"27","author":[{"given":"Linan","family":"Cheng","sequence":"first","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zheyu","family":"Xing","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Di","family":"Song","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Hu","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chunyue","family":"Wang","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-7857-3106","authenticated-orcid":false,"given":"Yuqing","family":"Chen","sequence":"additional","affiliation":[{"name":"Renal Division, Peking University First Hospital, No. 8, Xishiku Street, Xicheng District, Beijing 100034, China"},{"name":"Institute of Nephrology, Peking University, Beijing 100034, China"},{"name":"Key Laboratory of Renal Disease, Ministry of Health of China, Beijing 100034, China"},{"name":"Key Laboratory of CKD Prevention and Treatment, Ministry of Education of China, Beijing 100034, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,7,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"3789","DOI":"10.1016\/j.cell.2024.06.029","article-title":"Diabetes mellitus-Progress and opportunities in the evolving epidemic","volume":"187","author":"Abel","year":"2024","journal-title":"Cell"},{"key":"ref_2","doi-asserted-by":"crossref","unstructured":"Jha, R., Lopez-Trevino, S., Kankanamalage, H.R., and Jha, J.C. 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