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Here we demonstrate that\n                    <jats:italic>Sema3a<\/jats:italic>\n                    is elevated in liver sinusoidal endothelial cells of animal models for obesity, type 2 diabetes and MASLD. In primary human liver sinusoidal endothelial cells, saturated fatty acids induce expression of\n                    <jats:italic>SEMA3A<\/jats:italic>\n                    , and loss of a single allele is sufficient to reduce hepatic fat content in diet-induced obese mice. We show that semaphorin-3A regulates the number of fenestrae through a signaling cascade that involves neuropilin-1 and phosphorylation of cofilin-1 by LIM domain kinase 1. Finally, inducible vascular deletion of\n                    <jats:italic>Sema3a<\/jats:italic>\n                    in adult diet-induced obese mice reduces hepatic fat content and elevates very low-density lipoprotein secretion. Thus, we identified a molecular pathway linking hyperlipidemia to microvascular defenestration and early development of MASLD.\n                  <\/jats:p>","DOI":"10.1038\/s44161-024-00487-z","type":"journal-article","created":{"date-parts":[[2024,6,14]],"date-time":"2024-06-14T06:04:10Z","timestamp":1718345050000},"page":"734-753","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":26,"title":["Semaphorin-3A regulates liver sinusoidal endothelial cell porosity and promotes hepatic steatosis"],"prefix":"10.1038","volume":"3","author":[{"given":"Daniel","family":"Eberhard","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8486-7722","authenticated-orcid":false,"given":"Sydney","family":"Balkenhol","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrea","family":"K\u00f6ster","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paula","family":"Follert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6398-038X","authenticated-orcid":false,"given":"Eric","family":"Upschulte","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Philipp","family":"Ostermann","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6711-5959","authenticated-orcid":false,"given":"Philip","family":"Kirschner","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8772-1799","authenticated-orcid":false,"given":"Celina","family":"Uhlemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0659-7798","authenticated-orcid":false,"given":"Iannis","family":"Charnay","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christina","family":"Preuss","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1419-7177","authenticated-orcid":false,"given":"Sandra","family":"Trenkamp","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bengt-Frederik","family":"Belgardt","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Timo","family":"Dickscheid","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Esposito","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8200-6382","authenticated-orcid":false,"given":"Michael","family":"Roden","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9844-8000","authenticated-orcid":false,"given":"Eckhard","family":"Lammert","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2024,6,14]]},"reference":[{"key":"487_CR1","doi-asserted-by":"publisher","first-page":"3313","DOI":"10.1007\/s00018-018-2860-6","volume":"75","author":"DH Ipsen","year":"2018","unstructured":"Ipsen, D. 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