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The peroxisomal catalase\u2013hydrogen peroxide complex system plays a role in the metabolism of ethanol, while the potential origin of hydrogen peroxide involved in ethanol oxidation by this system is not determined. As peroxisomal fatty acid \u03b2\u2010oxidation generates hydrogen peroxide and can be induced under ketogenic conditions, we hypothesize that induction of peroxisomal \u03b2\u2010oxidation might accelerate ethanol oxidation through increasing the supply of hydrogen peroxide. The study reveals a novel mechanism by which upregulation of peroxisomal \u03b2\u2010oxidation stimulates ethanol metabolism and induces liver triglyceride deposition in animals. Excessive oxidation of fatty acids by peroxisomes generates considerable hydrogen peroxide in mouse liver, which significantly enhances liver ethanol oxidation and induces hepatic triglyceride accumulation through elevating mitochondrial NADH\/NAD<jats:sup>+<\/jats:sup> ratio and suppressing mitochondrial fatty acid oxidation. Specific inhibition of peroxisomal \u03b2\u2010oxidation suppresses ethanol oxidation in the liver and attenuates ethanol\u2010induced hepatic steatosis in fasting mice. It is proposed that induction of peroxisomal \u03b2\u2010oxidation serves as a critical mechanism for alcohol\u2010induced hepatic lipid accumulation in animals under ketogenic state, and targeting peroxisomal \u03b2\u2010oxidation might be a potential pathway in treating alcoholic fatty liver through reducing the supply of hydrogen peroxide and suppressing peroxisomal ethanol oxidation.<\/jats:p>","DOI":"10.1096\/fba.2024-00211","type":"journal-article","created":{"date-parts":[[2025,5,2]],"date-time":"2025-05-02T11:57:30Z","timestamp":1746187050000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Induction of Peroxisomal \u03b2\u2010Oxidation as a Critical Mechanism for Ethanol\u2010Induced Hepatic Triglyceride Accumulation"],"prefix":"10.1096","volume":"7","author":[{"given":"Yida","family":"Zhang","sequence":"first","affiliation":[{"name":"School of Life Science Hunan University of Science and Technology  Xiangtan Hunan P. 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