{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T06:34:21Z","timestamp":1793255661684,"version":"4.5.0"},"reference-count":40,"publisher":"Wiley","issue":"20","license":[{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"},{"start":{"date-parts":[[2026,10,14]],"date-time":"2026-10-14T00:00:00Z","timestamp":1791936000000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82470504"],"award-info":[{"award-number":["82470504"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L246053"],"award-info":[{"award-number":["L246053"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005089","name":"Natural Science Foundation of Beijing Municipality","doi-asserted-by":"publisher","award":["L256071"],"award-info":[{"award-number":["L256071"]}],"id":[{"id":"10.13039\/501100005089","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2026,10,31]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>FAM3 metabolism regulating signaling molecule A (FAM3A) is ubiquitously expressed. However, its biological role remains largely unknown. This study investigated the regulatory roles of FAM3A in plasma triglyceride (TG) levels. Proteomics revealed upregulated lipid metabolism\u2010related proteins, including CD36 and TCF15, in skeletal muscle of FAM3A\u2010transgenic mice. Clinically, plasma FAM3A was reduced in patients with metabolic disorders. FAM3A\u2010transgenic mice and recombinant FAM3A (rcFAM3A) injection in mice significantly reduced plasma TG levels, upregulated tissue lipid uptake and lipid transporter expression in skeletal muscle. Microvascular endothelial cells (MVECs) from soleus and heart of FAM3A\u2010transgenic mice or rcFAM3A\u2010infused mice exhibited increased fatty acid (FA) uptake and trans\u2010endothelial transport. Accordingly, FAM3A increased CD36 and TCF15 expression in MVECs derived from soleus, and increased CD36 expression was also observed in both C2C12 and MVECs treated by FAM3A in\u00a0vitro. The siRNA\u2010mediated knockdown of TCF15 or CD36 effectively inhibited FA uptake. Notably, FAM3A increased the luminal localization and activity of lipoprotein lipase (LPL) in endothelium, enhancing plasma VLDL\u2010TG hydrolysis both in\u00a0vivo and in\u00a0vitro. However, FAM3A showed no effect on hepatic VLDL production or intestinal lipid absorption. Importantly, FAM3A exerted these effects primarily by activating PPAR\u03b1 signaling, as pharmacological blockage of PPAR\u03b1 with GW6471 inhibited FAM3A\u2010induced upregulation of CD36 and TCF15 expression, endothelial lumen LPL localization and activity, FA uptake and trans\u2010endothelial transport, and plasma TG clearance. Collectively, these findings reveal a pivotal role of FAM3A in plasma TG catabolism, identifying that the FAM3A\/PPAR\u03b1 axis drives LPL\u2010mediated TG lipolysis, lipid\u2010transendothelial delivery, and tissue FA uptake.<\/jats:p>","DOI":"10.1096\/fj.202602574r","type":"journal-article","created":{"date-parts":[[2026,10,15]],"date-time":"2026-10-15T06:52:53Z","timestamp":1792047173000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["<scp>FAM3A<\/scp>\n                    Inhibits Plasma Triglyceride Levels via Microvasculature\u2010Involved Enhancement of\n                    <scp>VLDL<\/scp>\n                    \u2010Triglyceride Hydrolysis and Lipid Uptake"],"prefix":"10.1096","volume":"40","author":[{"given":"Xiaohong","family":"Song","sequence":"first","affiliation":[{"name":"Department of Vascular Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wenxuan","family":"Xiang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiangyu","family":"Xian","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lichai","family":"Yuan","sequence":"additional","affiliation":[{"name":"Department of Computational Biology and Bioinformatics, Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jianqiang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Center for Biomarker Discovery and Validation, National Infrastructure for Translational Medicine Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bintao","family":"Qiu","sequence":"additional","affiliation":[{"name":"Institute of Clinical Medicine, Center for Biomarker Discovery and Validation, National Infrastructure for Translational Medicine Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dan","family":"Yang","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"Department of Computational Biology and Bioinformatics, Institute of Medicinal Plant Development Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0704-5469","authenticated-orcid":false,"given":"Yuehong","family":"Zheng","sequence":"additional","affiliation":[{"name":"Department of Vascular Surgery Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"State Key Laboratory of Complex Severe and Rare Diseases Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College  Beijing China"},{"name":"National Infrastructures for Translational Medicine, Institute of Clinical Medicine Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences  Beijing China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,10,14]]},"reference":[{"key":"e_1_2_10_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)41685-2"},{"key":"e_1_2_10_3_1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpendo.90920.2008"},{"key":"e_1_2_10_4_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)40750-3"},{"key":"e_1_2_10_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)42640-9"},{"key":"e_1_2_10_6_1","doi-asserted-by":"publisher","DOI":"10.1084\/jem.20211314"},{"key":"e_1_2_10_7_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10071833"},{"key":"e_1_2_10_8_1","doi-asserted-by":"publisher","DOI":"10.7570\/jomes23064"},{"key":"e_1_2_10_9_1","first-page":"14","article-title":"Hericium Erinaceus Protein Alleviates High\u2010Fat Diet\u2010Induced Hepatic Lipid Accumulation and Oxidative Stress In\u00a0Vivo","volume":"14","author":"Lu H.","year":"2025","journal-title":"Food"},{"key":"e_1_2_10_10_1","doi-asserted-by":"publisher","DOI":"10.1006\/geno.2002.6816"},{"key":"e_1_2_10_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2017.12.001"},{"key":"e_1_2_10_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1753-4887.2011.00457.x"},{"key":"e_1_2_10_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s40779-024-00543-6"},{"key":"e_1_2_10_14_1","doi-asserted-by":"publisher","DOI":"10.1002\/hep.26945"},{"key":"e_1_2_10_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155372"},{"key":"e_1_2_10_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.metabol.2022.155292"},{"key":"e_1_2_10_17_1","doi-asserted-by":"publisher","DOI":"10.2337\/db19-1038"},{"key":"e_1_2_10_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41419-025-08298-1"},{"key":"e_1_2_10_19_1","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvp323"},{"key":"e_1_2_10_20_1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M031963"},{"key":"e_1_2_10_21_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1967.sp008211"},{"key":"e_1_2_10_22_1","doi-asserted-by":"publisher","DOI":"10.1016\/0003-2697(75)90488-1"},{"key":"e_1_2_10_23_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M403240200"},{"key":"e_1_2_10_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)38790-3"},{"key":"e_1_2_10_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/nm0395-221"},{"key":"e_1_2_10_26_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2275(20)37190-X"},{"key":"e_1_2_10_27_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.114.013721"},{"key":"e_1_2_10_28_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00003.2009"},{"key":"e_1_2_10_29_1","doi-asserted-by":"publisher","DOI":"10.1152\/physiol.00042.2012"},{"key":"e_1_2_10_30_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000255691.76142.4a"},{"key":"e_1_2_10_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.01.015"},{"key":"e_1_2_10_32_1","first-page":"110","article-title":"PPARgamma in the Endothelium Regulates Metabolic Responses to High\u2010Fat Diet in Mice","volume":"119","author":"Kanda T.","year":"2009","journal-title":"Journal of Clinical Investigation"},{"key":"e_1_2_10_33_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature08945"},{"key":"e_1_2_10_34_1","doi-asserted-by":"publisher","DOI":"10.1038\/nature11464"},{"key":"e_1_2_10_35_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M110.174458"},{"key":"e_1_2_10_36_1","doi-asserted-by":"publisher","DOI":"10.1097\/MOL.0b013e32834d0b33"},{"key":"e_1_2_10_37_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms20184378"},{"key":"e_1_2_10_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jlr.2025.100806"},{"key":"e_1_2_10_39_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2024.150481"},{"key":"e_1_2_10_40_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-023-41177-x"},{"key":"e_1_2_10_41_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-019-09746-1"}],"container-title":["The FASEB Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202602574R","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/full-xml\/10.1096\/fj.202602574R","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/pdf\/10.1096\/fj.202602574R","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,10,29]],"date-time":"2026-10-29T05:50:37Z","timestamp":1793253037000},"score":1,"resource":{"primary":{"URL":"https:\/\/faseb.onlinelibrary.wiley.com\/doi\/10.1096\/fj.202602574R"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,10,14]]},"references-count":40,"journal-issue":{"issue":"20","published-print":{"date-parts":[[2026,10,31]]}},"alternative-id":["10.1096\/fj.202602574R"],"URL":"https:\/\/doi.org\/10.1096\/fj.202602574r","archive":["Portico"],"relation":{},"ISSN":["0892-6638","1530-6860"],"issn-type":[{"value":"0892-6638","type":"print"},{"value":"1530-6860","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,10,14]]},"assertion":[{"value":"2026-05-21","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-09-28","order":2,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2026-10-14","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e72357"}}