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Monobutyrin (MB), a food additive found in butter and cod liver oil, possesses lipid-regulating properties. This study aimed to explore the alleviating effect of MB on liver oxidative injury and lipid metabolism in obese mice induced by a high-fat diet (HFD). The results showed that MB administration (1 or 2\u2009g\/kg body weight (BW)) for 8 weeks significantly reduced body weight, improved hepatic lipid metabolism via activation of the peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1) signaling pathway, and stabilized liver mitochondrial ultrastructure to alleviate oxidative liver injury by triggering mitochondrial autophagy through regulation of microtubule-associated protein 1A\/1B-light chain 3 (LC3) and ubiquitin-binding protein (P62) in mice. Moreover, MB might increase the abundance of beneficial bacteria, promote short-chain fatty acid levels, and alleviate high-fat induced obesity via the gut-liver axis. These findings provide a novel insight into MB as an intervention strategy for hepatic metabolic disorders.<\/jats:p>","DOI":"10.1038\/s41538-025-00524-6","type":"journal-article","created":{"date-parts":[[2025,7,29]],"date-time":"2025-07-29T18:43:41Z","timestamp":1753814621000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Monobutyrin can alleviate hepatic lipid dysmetabolism and improve liver mitochondrial ultrastructure and autophagy in high-fat diet mice"],"prefix":"10.1038","volume":"9","author":[{"given":"Yuqing","family":"Zhang","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoteng","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haidong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kexin","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ji","family":"Qiu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minyao","family":"Zhou","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Minqi","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2025,7,29]]},"reference":[{"key":"524_CR1","doi-asserted-by":"publisher","first-page":"851","DOI":"10.1016\/S2468-1253(22)00165-0","volume":"7","author":"K Riazi","year":"2022","unstructured":"Riazi, K. et al. 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