Adipogenin promotes the development of lipid droplets by binding a dodecameric seipin complex
The microprotein adipogenin (Adig) is predominantly expressed in adipose tissues. Here, we found that Adig interacts with seipin to form a stable, rigid complex. We present the structure of the seipin-Adig complex at an overall resolution of ~3.0 angstroms. The structure revealed that mammalian seipin assembles into two distinct oligomeric forms: undecamers and dodecamers. Adig selectively bound to the dodecameric form and enhanced seipin assembly by bridging and stabilizing adjacent subunits. Functionally, this complex promoted lipid droplet development at both early and late stages. In transgenic mice, adipocyte-specific overexpression of Adig increased fat mass and enlarged lipid droplets, whereas Adig deletion disrupted triglyceride accumulation in brown adipose tissues. Thus, Adig can modulate lipid storage through its structural and functional interactions with seipin.
Authors
- Ábel Szkalisity (ORCID: https://orcid.org/0000-0001-8388-5884)
- Yang Li (ORCID: https://orcid.org/0000-0001-9601-4885)
- Csaba Vörös (ORCID: https://orcid.org/0000-0002-6198-693X)
- Nolwenn Joffin (ORCID: https://orcid.org/0000-0003-2574-2089)
- Chanmin Joung (ORCID: https://orcid.org/0000-0003-0004-3441)
- Kristiina Kanerva (ORCID: https://orcid.org/0000-0003-1680-9448)
- Xavier Prasanna (ORCID: https://orcid.org/0000-0003-2270-5493)
- Chen Liu (ORCID: https://orcid.org/0000-0002-5922-0951)
- Zhao V. Wang (ORCID: https://orcid.org/0000-0002-9904-9538)
- Richard Wynn (ORCID: https://orcid.org/0000-0002-1879-2136)
- Dayoung Oh (ORCID: https://orcid.org/0000-0003-0687-6479)
- Ruth Gordillo (ORCID: https://orcid.org/0000-0001-6533-2493)
- Toshiharu Onodera (ORCID: https://orcid.org/0000-0002-4439-0077)
- Lauri Vanharanta (ORCID: https://orcid.org/0000-0002-7902-0009)
- Jan‐Bernd Funcke (ORCID: https://orcid.org/0000-0002-2596-3167)
- Ayanna Cobb
- Leon G. Straub (ORCID: https://orcid.org/0000-0001-6738-0130)
- Yan Han (ORCID: https://orcid.org/0000-0002-1207-7756)
- Elina Ikonen (ORCID: https://orcid.org/0000-0001-8382-1135)
- Dae-Seok Kim (ORCID: https://orcid.org/0000-0002-5477-3952)
- W. Mike Henne (ORCID: https://orcid.org/0000-0002-2135-2799)
- Min Kim (ORCID: https://orcid.org/0000-0002-0271-0124)
- Oleg Varlamov (ORCID: https://orcid.org/0000-0003-0294-215X)
- Philipp E. Scherer (ORCID: https://orcid.org/0000-0003-0680-3392)
- Andrea R. Nawrocki (ORCID: https://orcid.org/0000-0003-1348-3999)
- Ilpo Vattulainen (ORCID: https://orcid.org/0000-0001-7408-3214)
- Waldemar Kulig (ORCID: https://orcid.org/0000-0001-7568-0029)
- Shiuhwei Chen
- Joel Goodman (ORCID: https://orcid.org/0000-0001-5483-202X)
- Shangang Zhao (ORCID: https://orcid.org/0000-0002-9209-8206)
- Chao Li (ORCID: https://orcid.org/0000-0002-2060-4835)
- Yan Li (ORCID: https://orcid.org/0000-0002-3077-8097)
- Joselin Velasco
- Davide La Padula (ORCID: https://orcid.org/0009-0001-9166-6152)
- Xue‐Nan Sun (ORCID: https://orcid.org/0000-0003-2588-6648)
- May-Yun Wang
- Megan Virostek (ORCID: https://orcid.org/0009-0005-4968-2529)
- Kaitlynn Gov (ORCID: https://orcid.org/0000-0003-1140-3932)
Institutions
- Oregon National Primate Research Center (US)
- City Of Hope National Medical Center (US)
- University of Helsinki (FI)
- The University of Texas at San Antonio Health Science Center (US)
- HUN-REN Szegedi Biológiai Kutatóközpont (HU)
- Magna Graecia University (IT)
- Springhouse (US)
- Minerva Foundation (FI)
- Ulsan National Institute of Science and Technology (KR)
- The University of Texas Southwestern Medical Center (US)
- The University of Osaka (JP)
Publication Details
- Journal
- Science
- Published
- 2025-11-06
- DOI
- https://doi.org/10.1126/science.adr9755
- Citations
- 7
- Primary Topic
- Lipid metabolism and biosynthesis
- Type
- article
- Field-Weighted Citation Impact
- 7.78