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Here we demonstrated that GPR182, a receptor in lymphatic endothelial cells (LECs), mediates dietary fat absorption. GPR182 knockout mice are resistant to dietary-induced obesity. GPR182 ablation in mice leads to poor lipid absorption and thereby a delay in growth during development. GPR182 binds and endocytoses lipoproteins broadly. Mechanistically, loss of GPR182 prevents chylomicrons from entering the lacteal lumen of the small intestine. GPR182 blockage with a monoclonal antibody (mAb) protects mice from dietary induced obesity. Together, our study identifies GPR182 as a lipoprotein receptor that mediates dietary fat absorption.<\/jats:p>","DOI":"10.1101\/2025.02.03.634329","type":"posted-content","created":{"date-parts":[[2025,2,7]],"date-time":"2025-02-07T19:25:19Z","timestamp":1738956319000},"source":"Crossref","is-referenced-by-count":1,"title":["GPR182 is a lipoprotein receptor for dietary fat absorption"],"prefix":"10.64898","author":[{"given":"Zhiwei","family":"Sun","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J","family":"Torphy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emily N","family":"Miller","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anza","family":"Darehshouri","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac","family":"Vigil","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taichi","family":"Terai","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eck","family":"Eleanor","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi","family":"Sun","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yujie","family":"Guo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elliott J","family":"Yee","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junyi","family":"Hu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9065-7895","authenticated-orcid":false,"given":"Ross M","family":"Kedl","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika L","family":"Lasda","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6299-179X","authenticated-orcid":false,"given":"Jay R","family":"Hesselberth","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"MacLean","family":"Paul","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kimberley D","family":"Bruce","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gwendalyn J","family":"Randolph","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard D","family":"Schulick","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1434-6590","authenticated-orcid":false,"given":"Yuwen","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"54368","reference":[{"key":"2025031301205691000_2025.02.03.634329v1.1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-022-00676-y"},{"key":"2025031301205691000_2025.02.03.634329v1.2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.036"},{"key":"2025031301205691000_2025.02.03.634329v1.3","doi-asserted-by":"publisher","DOI":"10.1038\/s41572-019-0106-z"},{"key":"2025031301205691000_2025.02.03.634329v1.4","doi-asserted-by":"publisher","DOI":"10.1038\/nrgastro.2017.79"},{"key":"2025031301205691000_2025.02.03.634329v1.5","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2017.07.020"},{"key":"2025031301205691000_2025.02.03.634329v1.6","doi-asserted-by":"publisher","DOI":"10.1172\/JCI71610"},{"key":"2025031301205691000_2025.02.03.634329v1.7","doi-asserted-by":"publisher","DOI":"10.1111\/j.1749-6632.2010.05716.x"},{"key":"2025031301205691000_2025.02.03.634329v1.8","doi-asserted-by":"publisher","DOI":"10.1126\/science.aap9331"},{"key":"2025031301205691000_2025.02.03.634329v1.9","doi-asserted-by":"crossref","unstructured":"S. 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