{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"bioRxiv"}],"indexed":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T21:17:47Z","timestamp":1768511867575,"version":"3.49.0"},"posted":{"date-parts":[[2024,7,26]]},"group-title":"Cell Biology","reference-count":49,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T00:00:00Z","timestamp":1721952000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/www.biorxiv.org\/about\/FAQ#license"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2024,7,26]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>Adipogenin (Adig) is an evolutionarily conserved microprotein and is highly expressed in adipose tissues and testis. Here, we identify Adig as a critical regulator for lipid droplet formation in adipocytes. We determine that Adig interacts directly with seipin, leading to the formation of a rigid complex. We solve the structure of the seipin\/Adig complex by Cryo-EM at 2.98\u00c5 overall resolution. Surprisingly, seipin can form two unique oligomers, undecamers and dodecamers. Adig selectively binds to the dodecameric seipin complex. We further find that Adig promotes seipin assembly by stabilizing and bridging adjacent seipin subunits. Functionally, Adig plays a key role in generating lipid droplets in adipocytes. In mice, inducible overexpression of Adig in adipocytes substantially increases fat mass, with enlarged lipid droplets. It also elevates thermogenesis during cold exposure. In contrast, inducible adipocyte-specific Adig knockout mice manifest aberrant lipid droplet formation in brown adipose tissues and impaired cold tolerance.<\/jats:p>","DOI":"10.1101\/2024.07.25.605195","type":"posted-content","created":{"date-parts":[[2024,7,26]],"date-time":"2024-07-26T11:05:13Z","timestamp":1721991913000},"source":"Crossref","is-referenced-by-count":6,"title":["Adipogenin Dictates Adipose Tissue Expansion by Facilitating the Assembly of a Dodecameric Seipin Complex"],"prefix":"10.64898","author":[{"given":"Chao","family":"Li","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xue-Nan","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jan-Bernd","family":"Funcke","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lauri","family":"Vanharanta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nolwenn","family":"Joffin","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xavier","family":"Prasanna","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Megan","family":"Paredes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chanmin","family":"Joung","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ruth","family":"Gordillo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Csaba","family":"V\u00f6r\u00f6s","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Waldemar","family":"Kulig","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leon","family":"Straub","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shuiwei","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joselin","family":"Velasco","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ayanna","family":"Cobb","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Davide La","family":"Padula","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"May-Yun","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Toshiharu","family":"Onodera","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Oleg","family":"Varlamov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yang","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chen","family":"Liu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrea R.","family":"Nawrocki","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shangang","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Da Young","family":"Oh","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhao V.","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joel M.","family":"Goodman","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"R. Max","family":"Wynn","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ilpo","family":"Vattulainen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yan","family":"Han","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elina","family":"Ikonen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Philipp E.","family":"Scherer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2024072907301680000_2024.07.25.605195v1.1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210062200"},{"key":"2024072907301680000_2024.07.25.605195v1.2","doi-asserted-by":"publisher","DOI":"10.1007\/s11010-005-3673-0"},{"key":"2024072907301680000_2024.07.25.605195v1.3","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2004.10.200"},{"key":"2024072907301680000_2024.07.25.605195v1.4","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.abb.2015.09.019","article-title":"Expression, regulation and functional assessment of the 80 amino acid Small Adipocyte Factor 1 (Smaf1) protein in adipocytes","volume":"590","year":"2016","journal-title":"Archives of biochemistry and biophysics"},{"key":"2024072907301680000_2024.07.25.605195v1.5","doi-asserted-by":"crossref","first-page":"10494","DOI":"10.1038\/ncomms10494","article-title":"Genome-wide meta-analysis uncovers novel loci influencing circulating leptin levels","volume":"7","year":"2016","journal-title":"Nature communications"},{"key":"2024072907301680000_2024.07.25.605195v1.6","doi-asserted-by":"crossref","first-page":"108810","DOI":"10.1016\/j.celrep.2021.108810","article-title":"Phenotypic characterization of Adig null mice suggests roles for adipogenin in the regulation of fat mass accrual and leptin secretion","volume":"34","year":"2021","journal-title":"Cell reports"},{"key":"2024072907301680000_2024.07.25.605195v1.7","doi-asserted-by":"publisher","DOI":"10.1038\/s41556-024-01364-4"},{"key":"2024072907301680000_2024.07.25.605195v1.8","doi-asserted-by":"crossref","first-page":"912","DOI":"10.1016\/j.tcb.2021.06.003","article-title":"Seipin: harvesting fat and keeping adipocytes healthy","volume":"31","year":"2021","journal-title":"Trends in cell biology"},{"key":"2024072907301680000_2024.07.25.605195v1.9","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.200711136"},{"key":"2024072907301680000_2024.07.25.605195v1.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0704154104"},{"key":"2024072907301680000_2024.07.25.605195v1.11","doi-asserted-by":"crossref","first-page":"2902","DOI":"10.1038\/s41467-019-10835-4","article-title":"Dietary fatty acids promote lipid droplet diversity through seipin enrichment in an ER subdomain","volume":"10","year":"2019","journal-title":"Nature communications"},{"key":"2024072907301680000_2024.07.25.605195v1.12","doi-asserted-by":"crossref","first-page":"e1001364","DOI":"10.1371\/journal.pgen.1001364","article-title":"Tissue-autonomous function of Drosophila seipin in preventing ectopic lipid droplet formation","volume":"7","year":"2011","journal-title":"PLoS genetics"},{"key":"2024072907301680000_2024.07.25.605195v1.13","doi-asserted-by":"publisher","DOI":"10.2337\/db13-0729"},{"key":"2024072907301680000_2024.07.25.605195v1.14","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr205"},{"key":"2024072907301680000_2024.07.25.605195v1.15","doi-asserted-by":"publisher","DOI":"10.1038\/ng585"},{"key":"2024072907301680000_2024.07.25.605195v1.16","doi-asserted-by":"crossref","unstructured":"H. Wang et al., Seipin is required for converting nascent to mature lipid droplets. eLife 5, (2016).","DOI":"10.7554\/eLife.16582"},{"key":"2024072907301680000_2024.07.25.605195v1.17","doi-asserted-by":"publisher","DOI":"10.15252\/embj.201695170"},{"key":"2024072907301680000_2024.07.25.605195v1.18","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.05.016"},{"key":"2024072907301680000_2024.07.25.605195v1.19","doi-asserted-by":"crossref","first-page":"194","DOI":"10.1038\/s41594-021-00718-y","article-title":"Seipin forms a flexible cage at lipid droplet formation sites","volume":"29","year":"2022","journal-title":"Nature structural & molecular biology"},{"key":"2024072907301680000_2024.07.25.605195v1.20","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2018.09.010"},{"key":"2024072907301680000_2024.07.25.605195v1.21","doi-asserted-by":"crossref","first-page":"e99","DOI":"10.1002\/cpcb.99","article-title":"A Sensitive and Quantitative mKeima Assay for Mitophagy via FACS","volume":"86","year":"2020","journal-title":"Current protocols in cell biology"},{"key":"2024072907301680000_2024.07.25.605195v1.22","doi-asserted-by":"crossref","first-page":"1792","DOI":"10.1038\/nprot.2017.065","article-title":"Electron microscopy using the genetically encoded APEX2 tag in cultured mammalian cells","volume":"12","year":"2017","journal-title":"Nature protocols"},{"key":"2024072907301680000_2024.07.25.605195v1.23","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/nprot.2006.42","article-title":"The fluorescence protease protection (FPP) assay to determine protein localization and membrane topology","volume":"1","year":"2006","journal-title":"Nature protocols"},{"key":"2024072907301680000_2024.07.25.605195v1.24","doi-asserted-by":"crossref","first-page":"1140","DOI":"10.1126\/science.aay0262","article-title":"Pervasive functional translation of noncanonical human open reading frames","volume":"367","year":"2020","journal-title":"Science (New York, N.Y.)"},{"key":"2024072907301680000_2024.07.25.605195v1.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2015.01.009"},{"key":"2024072907301680000_2024.07.25.605195v1.26","doi-asserted-by":"publisher","DOI":"10.1016\/j.devcel.2019.10.006"},{"key":"2024072907301680000_2024.07.25.605195v1.27","doi-asserted-by":"crossref","unstructured":"I. G. Castro et al., Promethin Is a Conserved Seipin Partner Protein. Cells 8, (2019).","DOI":"10.3390\/cells8030268"},{"key":"2024072907301680000_2024.07.25.605195v1.28","doi-asserted-by":"crossref","first-page":"5892","DOI":"10.1038\/s41467-021-26162-6","article-title":"Mechanism of lipid droplet formation by the yeast Sei1\/Ldb16 Seipin complex","volume":"12","year":"2021","journal-title":"Nature communications"},{"key":"2024072907301680000_2024.07.25.605195v1.29","doi-asserted-by":"publisher","DOI":"10.1021\/bi1013003"},{"key":"2024072907301680000_2024.07.25.605195v1.30","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.201809067"},{"key":"2024072907301680000_2024.07.25.605195v1.31","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R023754"},{"key":"2024072907301680000_2024.07.25.605195v1.32","doi-asserted-by":"publisher","DOI":"10.1038\/ng1313"},{"key":"2024072907301680000_2024.07.25.605195v1.33","doi-asserted-by":"publisher","DOI":"10.2337\/db08-0184"},{"key":"2024072907301680000_2024.07.25.605195v1.34","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M017566"},{"key":"2024072907301680000_2024.07.25.605195v1.35","unstructured":"J. Abramson et al., Accurate structure prediction of biomolecular interactions with AlphaFold 3. Nature, (2024)."},{"key":"2024072907301680000_2024.07.25.605195v1.36","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pbio.3000998"},{"key":"2024072907301680000_2024.07.25.605195v1.37","doi-asserted-by":"publisher","DOI":"10.1038\/nm.2297"},{"key":"2024072907301680000_2024.07.25.605195v1.38","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M052746"},{"key":"2024072907301680000_2024.07.25.605195v1.39","doi-asserted-by":"crossref","first-page":"100971","DOI":"10.1016\/j.molmet.2020.02.014","article-title":"Berardinelli-Seip congenital lipodystrophy 2\/SEIPIN determines brown adipose tissue maintenance and thermogenic programing","volume":"36","year":"2020","journal-title":"Mol Metab"},{"key":"2024072907301680000_2024.07.25.605195v1.40","doi-asserted-by":"crossref","first-page":"35487","DOI":"10.1038\/srep35487","article-title":"Seipin deficiency alters brown adipose tissue thermogenesis and insulin sensitivity in a non-cell autonomous mode","volume":"6","year":"2016","journal-title":"Sci Rep"},{"key":"2024072907301680000_2024.07.25.605195v1.41","doi-asserted-by":"publisher","DOI":"10.1002\/pro.2860"},{"key":"2024072907301680000_2024.07.25.605195v1.42","doi-asserted-by":"crossref","first-page":"102606","DOI":"10.1016\/j.sbi.2023.102606","article-title":"Structure and function of lipid droplet assembly complexes","volume":"80","year":"2023","journal-title":"Curr Opin Struct Biol"},{"key":"2024072907301680000_2024.07.25.605195v1.43","doi-asserted-by":"crossref","unstructured":"V. Zoni et al., Seipin accumulates and traps diacylglycerols and triglycerides in its ring-like structure. Proceedings of the National Academy of Sciences of the United States of America 118, (2021).","DOI":"10.1073\/pnas.2017205118"},{"key":"2024072907301680000_2024.07.25.605195v1.44","doi-asserted-by":"crossref","unstructured":"S. Kim et al., Seipin transmembrane segments critically function in triglyceride nucleation and lipid droplet budding from the membrane. Elife 11, (2022).","DOI":"10.7554\/eLife.75808"},{"key":"2024072907301680000_2024.07.25.605195v1.45","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1324025111"},{"key":"2024072907301680000_2024.07.25.605195v1.46","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awn216"},{"key":"2024072907301680000_2024.07.25.605195v1.47","doi-asserted-by":"crossref","first-page":"e1002201","DOI":"10.1371\/journal.pgen.1002201","article-title":"A role for phosphatidic acid in the formation of \"supersized\" lipid droplets","volume":"7","year":"2011","journal-title":"PLoS genetics"},{"key":"2024072907301680000_2024.07.25.605195v1.48","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2014.03.028"},{"key":"2024072907301680000_2024.07.25.605195v1.49","doi-asserted-by":"crossref","first-page":"110213","DOI":"10.1016\/j.celrep.2021.110213","article-title":"Seipin localizes at endoplasmic-reticulum-mitochondria contact sites to control mitochondrial calcium import and metabolism in adipocytes","volume":"38","year":"2022","journal-title":"Cell reports"}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2024.07.25.605195","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T06:46:23Z","timestamp":1768459583000},"score":1,"resource":{"primary":{"URL":"http:\/\/biorxiv.org\/lookup\/doi\/10.1101\/2024.07.25.605195"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,7,26]]},"references-count":49,"URL":"https:\/\/doi.org\/10.1101\/2024.07.25.605195","relation":{},"subject":[],"published":{"date-parts":[[2024,7,26]]},"subtype":"preprint"}}