{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,12]],"date-time":"2026-10-12T12:47:04Z","timestamp":1791809224970,"version":"4.3.4"},"reference-count":37,"publisher":"Wiley","issue":"19","license":[{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T00:00:00Z","timestamp":1790380800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,10,15]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Succinate is a key metabolic intermediate in the tricarboxylic acid (TCA) cycle, which participates in energy metabolism. It accumulates under various pathological conditions and exerts regulatory effects through binding to its specific receptor GPR91. However, its specific function in sepsis\u2010associated acute kidney injury (SA\u2010AKI) remains unknown. Herein, we utilized GPR91 knockout (GPR91\u2212\/\u2212) mice and LPS\u2010induced SA\u2010AKI mouse models to elucidate the role and mechanisms of the succinate\u2010GPR91 axis in SA\u2010AKI. The results demonstrated significantly elevated succinate levels in the circulation of both SA\u2010AKI patients and mice. Exogenous succinate supplementation markedly mitigated renal inflammatory responses and histopathological damage in SA\u2010AKI mice. Notably, the deletion of GPR91 not only markedly exacerbated renal inflammation and tissue injury but also completely abolished the protective effects of exogenous succinate. Further mechanistic studies revealed that succinate suppresses activation of the PI3K\u2010AKT signaling pathway in a GPR91\u2010dependent manner, thereby reducing inflammation and attenuating renal damage in SA\u2010AKI. In conclusion, this study is the first to demonstrate that the succinate\u2010GPR91 axis exerts anti\u2010inflammatory and renal protective effects by inhibiting the PI3K\u2010AKT pathway, highlighting it as a potential therapeutic target for SA\u2010AKI.<\/jats:p>","DOI":"10.1096\/fj.202602357r","type":"journal-article","created":{"date-parts":[[2026,9,26]],"date-time":"2026-09-26T08:12:23Z","timestamp":1790410343000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Succinate Ameliorates Sepsis\u2010Associated Acute Kidney Injury by Mediating Inflammation via\n                    <scp>GPR91<\/scp>"],"prefix":"10.1096","volume":"40","author":[{"given":"Yiwei","family":"Xiong","sequence":"first","affiliation":[{"name":"Department of Nephrology Xiangya Hospital, Central South University  Changsha Hunan China"},{"name":"Key Laboratory of Organ Fibrosis of Hunan Province Central South University  Changsha Hunan 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