{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,9]],"date-time":"2026-10-09T14:54:10Z","timestamp":1791557650928,"version":"4.3.4"},"reference-count":47,"publisher":"Wiley","issue":"10","license":[{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"},{"start":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T00:00:00Z","timestamp":1789689600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100003995","name":"Natural Science Foundation of Anhui Province","doi-asserted-by":"publisher","award":["2108085MH284"],"award-info":[{"award-number":["2108085MH284"]}],"id":[{"id":"10.13039\/501100003995","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Liver International"],"published-print":{"date-parts":[[2026,10]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Background and Aim<\/jats:title>\n                    <jats:p>Liver fibrosis is a major global health burden with limited treatments. Emerging evidence suggests that metabolic dysregulation can create a state that makes the liver more prone to fibrosis. Carnitine, synthesized by \u03b3\u2010butyrobetaine hydroxylase (BBOX1), is crucial for fat metabolism, but the role of the BBOX1\u2010carnitine axis in liver fibrosis is unclear. This study aimed to elucidate the functional impact of BBOX1 deficiency on hepatic fibrogenesis and to delineate the underlying mechanistic pathway.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      We analysed human liver transcriptomic data.\n                      <jats:italic>Bbox1<\/jats:italic>\n                      knockout (KO) mice and wild\u2010type (WT) littermates were subjected to thioacetamide (TAA)\u2010induced liver fibrosis, with or without dietary L\u2010carnitine supplementation. Comprehensive analyses included metabolomic and transcriptomic profiling, histopathological evaluation, and focused investigation of calcium\u2010dependent signalling pathways.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      BBOX1 expression was significantly downregulated in human cirrhotic livers and correlated with reduced systemic carnitine levels.\n                      <jats:italic>Bbox1<\/jats:italic>\n                      \u2010KO mice exhibited profound hepatic carnitine depletion and a metabolically primed state. With TAA challenge, KO mice developed exacerbated liver fibrosis and inflammation compared to WT controls. This susceptibility was driven by the aberrant activation of the TRPC6\u2010Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/CAMK2B\u2010inflammatory signalling axis. Moreover, dietary L\u2010carnitine supplementation completely rescued the aggravated fibrotic phenotype in KO mice.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>\n                      BBOX1 is a key regulator of liver carnitine metabolism. Its deficiency creates a pro\u2010fibrotic state by abnormally activating the TRPC6\u2010Ca\n                      <jats:sup>2+<\/jats:sup>\n                      \/CAMK2B pathway. Our findings position carnitine as a protector of calcium balance in the liver and identify L\u2010carnitine supplementation as a potential targeted treatment to slow fibrosis progression.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/liv.70889","type":"journal-article","created":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T11:12:40Z","timestamp":1789729960000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["BBOX1 Deficiency Exacerbates Liver Fibrosis Through Carnitine Biosynthesis Disruption Rescued by Carnitine Supplementation"],"prefix":"10.1111","volume":"46","author":[{"ORCID":"https:\/\/orcid.org\/0009-0002-4713-1326","authenticated-orcid":false,"given":"Yuling","family":"Zhan","sequence":"first","affiliation":[{"name":"School of Life Science Bengbu Medical University  Bengbu China"},{"name":"Bengbu Medical University Key Laboratory of Cancer Research and Clinical 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