{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,18]],"date-time":"2026-09-18T22:15:08Z","timestamp":1789769708539,"version":"4.0.1"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T00:00:00Z","timestamp":1756339200000},"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","id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Background<\/jats:title><jats:p>Periodontitis is increasingly recognized as a risk factor for non-alcoholic fatty liver disease (NAFLD), yet the underlying mechanisms remain unclear. Oxidative stress and lipid metabolism dysregulation may serve as key pathological links. This study investigates the impact of periodontitis on NAFLD progression and identifies molecular targets involved in hepatic oxidative stress and lipid alterations.<\/jats:p><\/jats:sec><jats:sec><jats:title>Materials and methods<\/jats:title><jats:p>A rat model of periodontitis was established via molar ligation. Hepatic pathology was assessed using histological staining, biochemical assays, and oxidative stress markers. Proteomic analysis identified differentially expressed proteins (DEPs) associated with lipid metabolism and inflammation. Functional enrichment analysis, protein-protein interaction (PPI) network construction, and hub proteins identification were conducted.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Periodontitis significantly exacerbated hepatic lipid accumulation, fibrosis, and oxidative stress. Proteomic analysis identified 244 DEPs enriched in metabolic and inflammatory pathways. PPI network analysis revealed ACOX1, DBT, ACAA2, and HADHA as hub proteins. Downregulation of these proteins correlated with impaired lipid oxidation and hepatocellular injury in periodontitis-induced NAFLD.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Periodontitis accelerates NAFLD progression through oxidative stress and lipid metabolism dysfunction. ACOX1, DBT, ACAA2, and HADHA may serve as therapeutic targets. These findings highlight the importance of oral health in systemic metabolic disorders and suggest new intervention strategies.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1600015","type":"journal-article","created":{"date-parts":[[2025,8,28]],"date-time":"2025-08-28T04:10:35Z","timestamp":1756354235000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":10,"title":["Proteomics reveals periodontitis-driven oxidative stress and lipid metabolism disruption in 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