{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T23:52:21Z","timestamp":1790034741977,"version":"4.0.1"},"reference-count":36,"publisher":"Wiley","issue":"2","license":[{"start":{"date-parts":[[2026,1,20]],"date-time":"2026-01-20T00:00:00Z","timestamp":1768867200000},"content-version":"vor","delay-in-days":19,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,1,1]],"date-time":"2026-01-01T00:00:00Z","timestamp":1767225600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["physoc.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Physiological Reports"],"published-print":{"date-parts":[[2026,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Metabolic dysfunction\u2010associated steatotic liver disease (MASLD) is a growing public health concern characterized by hepatic triglyceride (TG) accumulation, inflammation, and fibrosis. Renalase is known for its role in blood pressure regulation and catecholamine metabolism, but recent evidence suggests broader cytokine\u2010like functions. Moreover, its involvement in MASLD remains unclear. In this study, we examined the effects of renalase deficiency on hepatic lipid metabolism in a Gubra Amylin NASH (GAN) diet\u2010induced MASLD model using renalase knockout (KO) mice. Our results show that renalase KO mice exhibited reduced hepatic TG levels, accompanied by decreased gene and protein expression of Srebf1 involved in lipid synthesis, and lower gene expressions of antioxidant and fibrosis markers in KO\u2010GAN compared with wild type (WT)\u2010GAN. Additionally, in\u00a0vitro experiments using AML12 cells with renalase knockdown confirmed reduced intracellular TG accumulation and lipid synthesis gene expression. Notably, the phosphorylation of Akt was significantly reduced in the liver of renalase\u2010KO mice, indicating that Akt signaling plays a critical role in the observed decrease in hepatic TG levels. These findings suggest that renalase regulates hepatic lipid metabolism through the Akt\u2013Srebf1 pathway, and its deficiency attenuates TG accumulation, suggesting that renalase may modulate early hepatic lipid deposition that progresses toward MASLD.<\/jats:p>","DOI":"10.14814\/phy2.70720","type":"journal-article","created":{"date-parts":[[2026,1,21]],"date-time":"2026-01-21T05:34:32Z","timestamp":1768973672000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":1,"title":["Renalase deficiency suppresses hepatic triglyceride accumulation in the progression to\n                    <scp>MASLD<\/scp>\n                    \/\n                    <scp>MASH<\/scp>\n                    by\n                    <scp>GAN<\/scp>\n                    diet in male mice"],"prefix":"10.14814","volume":"14","author":[{"given":"Yota","family":"Okano","sequence":"first","affiliation":[{"name":"Graduate School of Comprehensive Human Sciences 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Chiyoda\u2010ku Tokyo Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasushi","family":"Kawakami","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Tsukuba  Tsukuba Ibaraki Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazuhiro","family":"Takekoshi","sequence":"additional","affiliation":[{"name":"Faculty of Medicine University of Tsukuba  Tsukuba Ibaraki 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