{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T20:36:19Z","timestamp":1790627779959,"version":"4.1.0"},"reference-count":66,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2023,1,19]],"date-time":"2023-01-19T00:00:00Z","timestamp":1674086400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":["scijournals.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Sci Food Agric"],"published-print":{"date-parts":[[2023,3,30]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background<\/jats:title><jats:p>Dietary astaxanthin (AST) exhibits the ability to resist lipid accumulation and stimulate hepatic autophagy. Natural AST predominantly exists in stable esterified forms. More importantly, in our previous study, docosahexaenoic acid\u2010acylated AST monoester (AST\u2010DHA) possessed better stability, bioavailability, and neuroprotective ability than AST in free and diester form. However, the AST\u2010DHA mechanisms of action in regulating the obese phenotype and autophagy of the central nervous system remain unclear.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>High\u2010fat diet (HFD)\u2010fed C57BL\/6J mice were orally administered AST\u2010DHA (50\u2009mg\/kg body weight\/d) for 3\u2009days or 8\u2009weeks. AST\u2010DHA supplementation alleviated HFD\u2010induced abnormal body weight gain, significantly enhanced autophagy with an increased microtubule\u2010associated protein light chain 3 II\/I (LC3II\/I) ratio, and reduced the accumulation of p62\/sequestosome 1 (SQSTM1) in the hypothalamus rather than in the hippocampus. Mechanistically, AST\u2010DHA effectively promoted autophagy and autophagosome formation, and most notably rescued the HFD\u2010impaired autophagosome\u2010lysosome fusion (indicated by the colocalization of LC3 and LAMP1) by regulating mTOR\u2010 and AMPK\u2010induced phosphorylation of ULK1. Consequently, AST\u2010DHA enhanced hypothalamic autophagy, leading to pro\u2010opiomelanocortin (POMC) cleavage to produce alpha\u2010melanocyte\u2010stimulating hormone (\u03b1\u2010MSH).<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>This study identified AST\u2010DHA as an enhancer of autophagy that plays a beneficial role in restoring hypothalamic autophagy, and as a new potential therapeutic agent against HFD\u2010induced obesity. \u00a9 2023 Society of Chemical Industry.<\/jats:p><\/jats:sec>","DOI":"10.1002\/jsfa.12429","type":"journal-article","created":{"date-parts":[[2023,1,6]],"date-time":"2023-01-06T05:59:29Z","timestamp":1672984769000},"page":"2378-2388","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":11,"title":["Docosahexaenoic acid\u2010acylated astaxanthin monoester ameliorates chronic high\u2010fat diet\u2010induced autophagy dysfunction via <scp>ULK1<\/scp> pathway in the hypothalamus of mice"],"prefix":"10.1002","volume":"103","author":[{"given":"Xiaoxu","family":"Wang","sequence":"first","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China  Qingdao China"},{"name":"College of Marine Life Sciences, Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peixu","family":"Cong","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xincen","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China  Qingdao China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhigao","family":"Wang","sequence":"additional","affiliation":[{"name":"College of Food Science and Engineering, Ocean University of China  Qingdao 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