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Owing to the relatively low cytotoxicity compared with other chemical materials, several studies have explored the role of 2'-fucosyllactose (2'-FL), the most dominant component of human milk oligosaccharides. Here, we showed that 2'-FL reduced melanin levels in both melanocytic cells and a human skin equivalent three-dimensional in vitro model. Regarding the cellular and molecular mechanism, 2'-FL induced LC3I conversion into LC3II, an autophagy activation marker, followed by the formation of LC3II<jats:sup>+<\/jats:sup>\/PMEL<jats:sup>+<\/jats:sup> autophagosomes. Comparative transcriptome analysis provided a comprehensive understanding for the up- and downstream cellular processes and signaling pathways of the AMPK\u2013ULK1 signaling axis triggered by 2'-FL treatment. Moreover, 2'-FL activated the phosphorylation of AMPK at Thr172 and of ULK1 at Ser555, which were readily reversed in the presence of dorsomorphin, a specific AMPK inhibitor, with consequent reduction of the 2'-FL-mediated hypopigmentation. Taken together, these findings demonstrate that 2'-FL promotes melanin degradation by inducing autophagy through the AMPK\u2013ULK1 axis. Hence, 2'-FL may represent a new natural melanin-degrading agent for hyperpigmentation.<\/jats:p>","DOI":"10.1038\/s41598-022-17896-4","type":"journal-article","created":{"date-parts":[[2022,8,17]],"date-time":"2022-08-17T15:03:03Z","timestamp":1660748583000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["Human milk oligosaccharide 2'-fucosyllactose promotes melanin degradation via the autophagic AMPK\u2013ULK1 signaling axis"],"prefix":"10.1038","volume":"12","author":[{"given":"Hyojin","family":"Heo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byungsun","family":"Cha","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dongmin","family":"Jang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chaewon","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunwoo","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Byeong-Mun","family":"Kwak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Bum-Ho","family":"Bin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ji-Hwan","family":"Park","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mi-Gi","family":"Lee","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2022,8,17]]},"reference":[{"key":"17896_CR1","doi-asserted-by":"publisher","unstructured":"Slominski, A. 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