{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:04:05Z","timestamp":1790762645414,"version":"4.1.0"},"reference-count":69,"publisher":"MDPI AG","issue":"19","license":[{"start":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T00:00:00Z","timestamp":1790726400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Int. J. Mol. Sci.","IJMS"],"abstract":"<jats:p>Ceramides constitute approximately 50% of the lipid mass in the stratum corneum and are essential for epidermal permeability barrier function. In acne vulgaris, barrier disruption is accompanied by altered ceramide composition, yet the molecular mechanisms that connect acne-associated signals to specific changes in ceramide metabolism remain incompletely understood. This review integrates evidence from lipidomic profiling, enzymatic pathway characterization, and inflammatory signaling studies to examine how ceramide biosynthesis and turnover are modulated in acne-prone skin. Particular attention is directed to the elongation of very-long-chain fatty acids (VLCFAs) and their incorporation into ceramides by ceramide synthase 3 (CerS3). In cultured keratinocytes, Cutibacterium acnes (C. acnes)-derived short-chain fatty acids (SCFAs) have been reported to suppress CerS3 and 3-ketodihydrosphingosine reductase (KDSR) through peroxisome proliferator-activated receptor \u03b1 (PPAR\u03b1), limiting ultra-long-chain fatty acid (ULCFA) supply. We propose a working model in which SCFAs act via PPAR\u03b1 to upregulate ELOVL-family elongases while suppressing CerS3 and KDSR, reducing ULCFA-ceramides and compromising barrier integrity. The CerS3\u2013KDSR node is a candidate regulatory point coupling microbial metabolites to barrier impairment and inflammation. However, this model rests largely on in vitro evidence and requires in vivo validation. Clarifying these regulatory relationships may inform the development of barrier-restorative strategies as adjuncts to conventional acne therapy.<\/jats:p>","DOI":"10.3390\/ijms27198737","type":"journal-article","created":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T09:25:42Z","timestamp":1790760342000},"page":"8737","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Ceramide Metabolic Pathways and Their Regulation in Adolescent Acne Vulgaris"],"prefix":"10.3390","volume":"27","author":[{"ORCID":"https:\/\/orcid.org\/0009-0005-9579-7706","authenticated-orcid":false,"given":"Yvwei","family":"Gou","sequence":"first","affiliation":[{"name":"Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Fucheng Road, Haidian District, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6916-1596","authenticated-orcid":false,"given":"Hua","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Fucheng Road, Haidian District, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0009-1924-5925","authenticated-orcid":false,"given":"Xingyi","family":"Wu","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Fucheng Road, Haidian District, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0008-0782-4391","authenticated-orcid":false,"given":"Guolong","family":"Dong","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Fucheng Road, Haidian District, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Haodong","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Fucheng Road, Haidian District, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5344-3655","authenticated-orcid":false,"given":"Huanxiang","family":"Yuan","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Fucheng Road, Haidian District, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Li","family":"Li","sequence":"additional","affiliation":[{"name":"Beijing Key Laboratory of Plant Resource Research and Development, Beijing Technology and Business University, Fucheng Road, Haidian District, Beijing 100048, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,9,30]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"945","DOI":"10.1016\/j.jaad.2015.12.037","article-title":"Guidelines of Care for the Management of Acne Vulgaris","volume":"74","author":"Zaenglein","year":"2016","journal-title":"J. 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