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Nevertheless, the organ-specific modulation of lysolecithin remodeling in T2DM remains unexplored. Here, we investigate the LPC\/PC remodeling dynamics in a T2DM model and propose a novel therapeutic approach using an orally bioavailable peptide (SP6) derived from Spirulina platensis.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>LPC\/PC levels were analyzed by UHPLC-HRMS. Membrane fluidity, VEGF\/API5, LPCAT1, VE-cadherin, and GLUT1 were evaluated by merocyanine assay, qPCR, immunoblotting, and immunofluorescence. In vivo, T2DM was induced by a high-fat diet and streptozotocin, and SP6 was orally administered. Tissue lipidomics, GLUTs expression, and insulin secretion were assessed, with the latter also spatially characterized in pancreatic tissue by MALDI-MS imaging.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>High glucose induced LPC\/PC imbalance, enhanced membrane fluidity, impaired VEGF\/API5 expression, and hindered wound healing and VE-cadherin localization via LPCAT1 downregulation and subsequent impact on GLUT1 translocation. In vivo analysis of diabetic mice revealed a multi-organ influence of SP6 preserving LPCAT1 mRNA levels in pancreas, liver, skeletal muscle, and adipose tissue and a specific pattern of lysolecithin remodeling, with selective modulation of LPC 16:0, 18:0, and 20:4 in plasma. Finally, its effects in T2DM are mediated by preserving insulin secretion and glycemic control through increased ATP production.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These findings reveal tissue-specific lysolecithin reprogramming in T2DM development and identify LPCAT1-mediated lysolecithin remodeling as a mechanism involved in T2DM-related endothelial and metabolic dysfunction. SP6 modulates lipid metabolism, vascular integrity, and glucose regulation at the transcript level, suggesting its potential as a new preventive treatment for T2DM and its complications.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Graphical abstract<\/jats:title>\n                  <\/jats:sec>","DOI":"10.1186\/s12933-025-03053-4","type":"journal-article","created":{"date-parts":[[2026,1,18]],"date-time":"2026-01-18T08:14:25Z","timestamp":1768724065000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Lysolecithin reprogramming via LPCAT1 modulation restores endothelial function and prevents diabetes-associated dysmetabolism"],"prefix":"10.1186","volume":"25","author":[{"given":"Eduardo Maria","family":"Sommella","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Concetta","family":"Iside","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paola","family":"Di Pietro","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fabrizio","family":"Merciai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emanuela","family":"Salviati","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marina","family":"Sala","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angela Carmelita","family":"Abate","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antonio","family":"Damato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Massimiliano","family":"De Lucia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eleonora","family":"Venturini","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Valeria","family":"Prete","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Francesca","family":"Picone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paolo","family":"Poggio","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pasquale","family":"Mone","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michele","family":"Ciccarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gaetano","family":"Santulli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pietro","family":"Campiglia","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Carmine","family":"Vecchione","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Albino","family":"Carrizzo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,1,18]]},"reference":[{"key":"3053_CR1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2020.110708","volume":"131","author":"S Padhi","year":"2020","unstructured":"Padhi S, Nayak AK, Behera A. 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