{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T04:49:27Z","timestamp":1787028567078,"version":"build-2736575974"},"reference-count":40,"publisher":"MDPI AG","issue":"15","license":[{"start":{"date-parts":[[2025,8,5]],"date-time":"2025-08-05T00:00:00Z","timestamp":1754352000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100008728","name":"Japan Research Foundation for Clinical Pharmacology","doi-asserted-by":"publisher","award":["3-2418-009"],"award-info":[{"award-number":["3-2418-009"]}],"id":[{"id":"10.13039\/100008728","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100008728","name":"Japan Research Foundation for Clinical Pharmacology","doi-asserted-by":"publisher","award":["24K02579"],"award-info":[{"award-number":["24K02579"]}],"id":[{"id":"10.13039\/100008728","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["3-2418-009"],"award-info":[{"award-number":["3-2418-009"]}]},{"name":"Japan Society for the Promotion of Science (JSPS)","award":["24K02579"],"award-info":[{"award-number":["24K02579"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Tacrolimus (TAC)-induced chronic nephrotoxicity (TAC nephrotoxicity) remains a major contributor to late allograft dysfunction in kidney transplant recipients. Although detailed mechanisms remain incompletely understood, our previous metabolomic studies revealed disruptions in carnitine-related and redox pathways, suggesting impaired mitochondrial \u03b2-oxidation of fatty acids. To further characterize metabolic alterations associated with this condition, we conducted an untargeted lipidomic analysis of renal tissues using a murine model of TAC nephrotoxicity. TAC (1 mg\/kg\/day) or saline was subcutaneously administered to male ICR mice for 28 days, and kidney tissues were harvested for comprehensive lipidomic profiling. Lipidomic analysis was performed with liquid chromatography\u2013tandem mass spectrometry (p &lt; 0.05, n = 5\/group). Triacylglycerols (TGs) were the predominant lipid class identified. TAC-treated mice exhibited reduced levels of unsaturated TG species with low carbon numbers, whereas TGs with higher carbon numbers and various degrees of unsaturation were increased. All detected TGs containing docosahexaenoic acid (DHA) showed an increasing trend in TAC-treated kidneys. Although accumulation of polyunsaturated TGs has been previously observed in chronic kidney disease, the preferential increase in DHA-containing TGs appears to be a unique feature of TAC-induced nephrotoxicity. These results suggest that DHA-enriched TGs may serve as a metabolic signature of TAC nephrotoxicity and offer new insights into its pathophysiology.<\/jats:p>","DOI":"10.3390\/ijms26157549","type":"journal-article","created":{"date-parts":[[2025,8,6]],"date-time":"2025-08-06T07:45:11Z","timestamp":1754466311000},"page":"7549","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["DHA\u2013Triacylglycerol Accumulation in Tacrolimus-Induced Nephrotoxicity Identified by Lipidomic Profiling"],"prefix":"10.3390","volume":"26","author":[{"given":"Sho","family":"Nishida","sequence":"first","affiliation":[{"name":"Department of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Japan"},{"name":"Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0002-2309-265X","authenticated-orcid":false,"given":"Tamaki","family":"Ishima","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8274-848X","authenticated-orcid":false,"given":"Daiki","family":"Iwami","sequence":"additional","affiliation":[{"name":"Division of Renal Surgery and Transplantation, Department of Urology, Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryozo","family":"Nagai","sequence":"additional","affiliation":[{"name":"Jichi Medical University, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kenichi","family":"Aizawa","sequence":"additional","affiliation":[{"name":"Department of Translational Research, Clinical Research Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Japan"},{"name":"Clinical Pharmacology Center, Jichi Medical University Hospital, Shimotsuke 329-0498, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,8,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"217","DOI":"10.1016\/j.ejps.2017.12.017","article-title":"Tacrolimus: An updated review on delivering strategies for multifarious diseases","volume":"114","author":"Dheer","year":"2018","journal-title":"Eur. 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