{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T06:36:06Z","timestamp":1791441366175,"version":"4.3.3"},"reference-count":41,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T00:00:00Z","timestamp":1488326400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Commun"],"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Lipids are the primary components of the skin permeability barrier, which is the body\u2019s most powerful defensive mechanism against pathogens. Acylceramide (\n                    <jats:italic>\u03c9<\/jats:italic>\n                    -\n                    <jats:italic>O<\/jats:italic>\n                    -acylceramide) is a specialized lipid essential for skin barrier formation. Here, we identify\n                    <jats:italic>PNPLA1<\/jats:italic>\n                    as the long-sought gene involved in the final step of acylceramide synthesis, esterification of\n                    <jats:italic>\u03c9<\/jats:italic>\n                    -hydroxyceramide with linoleic acid, by cell-based assays. We show that increasing triglyceride levels by overproduction of the diacylglycerol acyltransferase DGAT2 stimulates acylceramide production, suggesting that triglyceride may act as a linoleic acid donor. Indeed, the\n                    <jats:italic>in vitro<\/jats:italic>\n                    analyses confirm that PNPLA1 catalyses acylceramide synthesis using triglyceride as a substrate. Mutant forms of PNPLA1 found in patients with ichthyosis exhibit reduced or no enzyme activity in either cell-based or\n                    <jats:italic>in vitro<\/jats:italic>\n                    assays. Altogether, our results indicate that PNPLA1 is directly involved in acylceramide synthesis as a transacylase, and provide important insights into the molecular mechanisms of skin barrier formation and of ichthyosis pathogenesis.\n                  <\/jats:p>","DOI":"10.1038\/ncomms14610","type":"journal-article","created":{"date-parts":[[2017,3,1]],"date-time":"2017-03-01T11:34:25Z","timestamp":1488368065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":114,"title":["PNPLA1 is a transacylase essential for the generation of the skin barrier lipid \u03c9-O-acylceramide"],"prefix":"10.1038","volume":"8","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-3702-1043","authenticated-orcid":false,"given":"Yusuke","family":"Ohno","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nozomi","family":"Kamiyama","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shota","family":"Nakamichi","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5889-0788","authenticated-orcid":false,"given":"Akio","family":"Kihara","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2017,3,1]]},"reference":[{"key":"BFncomms14610_CR1","doi-asserted-by":"publisher","first-page":"280","DOI":"10.1016\/j.bbalip.2013.11.007","volume":"1841","author":"KR Feingold","year":"2014","unstructured":"Feingold, K. 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