ORCID: https://orcid.org/0000-0002-7950-8952; Menezes, Filipe ORCID: https://orcid.org/0000-0002-7630-5447; Khasanova, Dina; Kang, Lingru; Wang, Chenxi; Ruiz-Trave, Julio ORCID: https://orcid.org/0009-0002-5752-7527; Sharma, Sapna ORCID: https://orcid.org/0000-0003-1039-8879; Khalil, Ahmed ORCID: https://orcid.org/0009-0000-2204-8636; Reichenbach, Valentin K. ORCID: https://orcid.org/0009-0004-4115-6201; Shi, Yingzi; Flatley, Andrew; Yan, Xiaocheng; Israel, Andreas; Dragano, Nathalia R. V. ORCID: https://orcid.org/0000-0002-6856-5468; Aguilar-Pimentel, Juan Antonio; Hoffmann, Anne Friederike ORCID: https://orcid.org/0000-0003-4964-3552; Ghosh, Adhideb ORCID: https://orcid.org/0000-0002-5160-4571; Noé, Falko ORCID: https://orcid.org/0009-0002-3360-5455; Wolfrum, Christian ORCID: https://orcid.org/0000-0002-3862-6805; Cucuruz, Sebastian; König, Ann-Christine; Burtscher, Ingo ORCID: https://orcid.org/0000-0002-0635-3507; Hauck, Stefanie M. ORCID: https://orcid.org/0000-0002-1630-6827; Lickert, Heiko; Hofmann, Susanna M. ORCID: https://orcid.org/0000-0001-7682-5840; Feederle, Regina ORCID: https://orcid.org/0000-0002-3981-367X; Schriever, Sonja C ORCID: https://orcid.org/0000-0001-5461-3214; Hernandez-Bautista, Rene ORCID: https://orcid.org/0000-0001-7065-2862; Sancar, Gencer ORCID: https://orcid.org/0000-0002-2098-0654; Cebrian-Serrano, Alberto; Tetko, Igor ORCID: https://orcid.org/0000-0002-6855-0012; Fuchs, Helmut; Gailus-Durner, Valérie; Blüher, Matthias; Hrabě de Angelis, Martin und Ussar, Siegfried ORCID: https://orcid.org/0000-0001-7575-0920
(2025):
NRAC controls CD36-mediated fatty acid uptake in adipocytes and lipid clearance in vivo.
In: EMBO Journal, Bd. 44: S. 5037-5065
[PDF, 3MB]
Abstract
Adipose tissue is a central organiser of systemic lipid homeostasis and a pharmacological target in obesity, orchestrating cellular responses to environmental cues. Nutritionally regulated adipose and cardiac enriched protein (NRAC) is a small adipocyte-specific transmembrane protein with unknown function. Here, we show that Nrac directly interacts with scavenger receptor CD36 via its first transmembrane domain. Forming a complex with CD36 and caveolin-1 under low extracellular fatty acid (FA) concentrations, NRAC modulates CD36-dependent fatty acid uptake in adipocytes. Upon increase in extracellular FA levels, NRAC is ubiquitinated and internalised, leading to CD36’s dissociation from caveolin-1 and clathrin-mediated endocytosis. This results in increased fatty acid uptake into fat cells, adipocyte hypertrophy, increased fat mass and elevated lipid clearance from the blood in chow-diet-fed mice. Finally, human NRAC expression and the intronic SNP rs12878589 are associated with body fat distribution and obesity. Together, these findings reveal a novel regulatory mechanism by which adipocytes sense and respond to extracellular fatty acid availability to fine-tune lipid uptake and storage at cellular and organismal level.
| Dokumententyp: | Zeitschriftenartikel |
|---|---|
| EU Funded Grant Agreement Number: | 101120466 |
| Fakultät: | Medizin > Munich Cluster for Systems Neurology (SyNergy) |
| Themengebiete: | 600 Technik, Medizin, angewandte Wissenschaften > 610 Medizin und Gesundheit |
| URN: | urn:nbn:de:bvb:19-epub-129925-0 |
| ISSN: | 0261-4189 |
| Sprache: | Englisch |
| Dokumenten ID: | 129925 |
| Datum der Veröffentlichung auf Open Access LMU: | 01. Dez. 2025 07:19 |
| Letzte Änderungen: | 01. Dez. 2025 07:19 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 390857198 |
| DFG: | Gefördert durch die Deutsche Forschungsgemeinschaft (DFG) - 209933838 |
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