{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T19:17:41Z","timestamp":1787944661338,"version":"build-2784847793"},"reference-count":41,"publisher":"MDPI AG","issue":"9","license":[{"start":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T00:00:00Z","timestamp":1787875200000},"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":["82270846"],"award-info":[{"award-number":["82270846"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"award":["82270846"],"award-info":[{"award-number":["82270846"]}],"id":[{"id":"https:\/\/ror.org\/01h0zpd94","id-type":"ROR","asserted-by":"publisher"}]},{"name":"National Science and Technology Major Project of China\/National Key Research and Development Program of China","award":["2025ZD0551806"],"award-info":[{"award-number":["2025ZD0551806"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Background\/Objectives: Hepatocyte proliferation during liver regeneration requires precise transcriptional coordination of metabolic reprogramming, but the key regulators governing this process remain largely unknown. Methods: Hepatocyte-specific retinoic acid receptor-related orphan receptor \u03b1 (ROR\u03b1) knockout (ROR\u03b1-LKO) mice were generated and subjected to two-thirds partial hepatectomy (PHx). Liver regeneration was assessed by liver-to-body weight ratio, histology, and proliferation markers (PCNA, Ki67, cyclin D1). Metabolic changes were evaluated by untargeted metabolomics, Seahorse extracellular flux analysis, and glycolytic enzyme activity assays. The molecular mechanism was investigated through RNA-seq analysis, qPCR, Western blotting, dual-luciferase reporter assays, CUT&amp;Tag-qPCR, and pharmacological inhibition. Results: ROR\u03b1 expression was transiently upregulated during the early phase and declined at the peak of hepatocyte proliferation. ROR\u03b1-LKO mice exhibited accelerated liver recovery and increased hepatocyte proliferation following a partial hepatectomy, without enhanced inflammation or fatty acid oxidation. Mechanistically, ROR\u03b1 directly binds to the promoter of Me1 to repress its transcription. Loss of ROR\u03b1 upregulates ME1, enhances glycolysis, and increases ATP production. Pharmacological inhibition of ME1 reversed these effects. Conclusions: The ROR\u03b1\u2013ME1 axis links transcriptional repression to metabolic reprogramming and may represent a therapeutic target for liver regeneration.<\/jats:p>","DOI":"10.3390\/genes17091029","type":"journal-article","created":{"date-parts":[[2026,8,28]],"date-time":"2026-08-28T18:33:52Z","timestamp":1787942032000},"page":"1029","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Hepatocyte-Specific ROR\u03b1 Deficiency Accelerates Liver Regeneration by Unleashing ME1-Driven Glycolysis"],"prefix":"10.3390","volume":"17","author":[{"given":"Hongmei","family":"Zhang","sequence":"first","affiliation":[{"name":"Institute of High Altitude Medicine, Center for High Altitude Medicine, High Altitude Medicine Key Laboratory of Sichuan Province, West China Hospital, Sichuan University, Chengdu 610041, China"},{"name":"Frontiers Science Center for Disease-Related Molecular Network, West China Hospital, Sichuan 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