{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,10]],"date-time":"2026-06-10T18:20:33Z","timestamp":1781115633644,"version":"3.54.1"},"reference-count":34,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T00:00:00Z","timestamp":1748476800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:sec><jats:title>Introduction<\/jats:title><jats:p>Alcoholic fatty liver disease (AFLD) is a significant global health concern caused by chronic and excessive alcohol consumption, leading to hepatic steatosis, inflammation, and metabolic disruption. Currently, there are limited effective therapeutic options. Kaempferol, a dietary flavonoid, has shown potential for regulating oxidative stress and lipid metabolism.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>In this study, C57BL\/6 mice (n = 12 per group) were assigned to control, ethanol-fed (AFLD), or ethanol plus kaempferol (KPF) groups. The AFLD model was induced using a modified Lieber-DeCarli diet with stepwise ethanol escalation and a final single binge dose. Kaempferol was administered at 20 mg\/kg\/day by gavage. Serum biochemical markers, liver histology, oxidative stress indices, and untargeted plasma metabolomics were assessed to evaluate KPF\u2019s protective effects.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>Kaempferol-treated mice exhibited significantly reduced alanine aminotransferase (ALT, p &amp;lt; 0.0001) and aspartate aminotransferase (AST, p &amp;lt; 0.05) levels compared to the AFLD group. Histological analysis revealed improved hepatic architecture and reduced lipid droplet accumulation. Kaempferol also enhanced antioxidant capacity, evidenced by reduced malondialdehyde (MDA, p &amp;lt; 0.05). Metabolomic profiling identified multiple altered metabolites associated with glycolysis, amino acid metabolism, and sphingolipid signaling.<\/jats:p><\/jats:sec><jats:sec><jats:title>Discussion<\/jats:title><jats:p>These findings indicate that kaempferol exerts protective effects against AFLD through multi-target regulation of oxidative stress and metabolic pathways. Our study provides systems-level evidence supporting kaempferol as a promising dietary-based intervention for AFLD management.<\/jats:p><\/jats:sec>","DOI":"10.3389\/fendo.2025.1610613","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T04:13:15Z","timestamp":1748491995000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Systems metabolic insights into kaempferol-mediated alleviation of alcoholic fatty liver 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