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Here, we show that hepatic phospho\u2010active ACLY correlates with overweight and Model for End\u2010stage Liver Disease score in humans. Wild\u2010type mice treated chronically with the ACLY inhibitor potassium hydroxycitrate exhibited delayed early mortality. In AML12 hepatocyte cultures, the ACLY inhibitors potassium hydroxycitrate, SB\u2010204990, and bempedoic acid fostered lipid accumulation, which was also observed in the liver of healthy\u2010fed mice treated with potassium hydroxycitrate. Analysis of soleus tissue indicated that potassium hydroxycitrate produced the modulation of wound healing processes. In\u00a0vivo, potassium hydroxycitrate modulated locomotor function toward increased wire hang performance and reduced rotarod performance in healthy\u2010fed mice, and improved locomotion in mice exposed to cardiotoxin\u2010induced muscle atrophy. Our findings implicate ACLY and ACLY inhibitors in different aspects of aging and muscle regeneration.<\/jats:p>","DOI":"10.1111\/acel.14205","type":"journal-article","created":{"date-parts":[[2024,5,18]],"date-time":"2024-05-18T04:41:03Z","timestamp":1716007263000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Hydroxycitrate delays early mortality in mice and promotes muscle regeneration while inducing a rich hepatic energetic status"],"prefix":"10.1111","volume":"23","author":[{"given":"Isabel","family":"Espadas","sequence":"first","affiliation":[{"name":"Andalusian Molecular Biology and Regenerative Medicine Centre\u2010CABIMER Universidad de Sevilla\u2010CSIC\u2010Universidad Pablo de Olavide  Seville Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mar\u00eda \u00c1ngeles","family":"C\u00e1liz\u2010Molina","sequence":"additional","affiliation":[{"name":"Andalusian Molecular Biology and 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