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Singh, I. ; Onogi, Y. ; Cardoso Micu Menezes, F.M. ; Khasanova, D. ; Kang, L. ; Wang, C. ; Ruiz-Trave, J. ; Sharma, S. ; Khalil, A. ; Reichenbach, V.K. ; Shi, Y. ; Flatley, A. ; Yan, X. ; Israel, A. ; Dragano, N.R.V. ; Aguilar-Pimentel, J.A. ; Hoffmann, A. ; Ghosh, A.* ; Noé, F.* ; Wolfrum, C.* ; Cucuruz, S. ; König, A.-C. ; Burtscher, I. ; Hauck, S.M. ; Lickert, H. ; Hofmann, S.M. ; Feederle, R. ; Schriever, S.C. ; Hernandez-Bautista, R. ; Sancar, G.* ; Cebrian Serrano, A. ; Tetko, I.V. ; Fuchs, H. ; Gailus-Durner, V. ; Blüher, M. ; Hrabě de Angelis, M. ; Ussar, S.

NRAC controls CD36-mediated fatty acid uptake in adipocytes and lipid clearance in vivo.

EMBO J. 44, 5037-5065 (2025)
Verlagsversion Forschungsdaten DOI PMC
Creative Commons Lizenzvertrag
Open Access Green möglich sobald Postprint bei der ZB eingereicht worden ist.
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.
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Publikationstyp Artikel: Journalartikel
Dokumenttyp Wissenschaftlicher Artikel
Schlagwörter Adipose Tissue ; Cd36 ; Clathrin-mediated Endocytosis ; Fatty Acid Uptake ; Hypertrophy; Adipose; Insulin; Obesity; Brown
Sprache englisch
Veröffentlichungsjahr 2025
HGF-Berichtsjahr 2025
ISSN (print) / ISBN 0261-4189
e-ISSN 1460-2075
Zeitschrift EMBO Journal, The
Quellenangaben Band: 44, Heft: 18, Seiten: 5037-5065 Artikelnummer: , Supplement: ,
Verlag Wiley
Verlagsort Heidelberg, Germany
Begutachtungsstatus Peer reviewed
Institut(e) Adipocytes & Metabolism (ADM)
Institute of Diabetes and Obesity (IDO)
Institute of Structural Biology (STB)
Institute of Epidemiology (EPI)
CF Monoclonal Antibodies (CF-MAB)
Institute of Experimental Genetics (IEG)
Helmholtz Institute for Metabolism, Obesity and Vascular Research (HI-MAG)
Institute of Diabetes and Regeneration Research (IDR)
CF Metabolomics & Proteomics (CF-MPC)
POF Topic(s) 30205 - Bioengineering and Digital Health
30201 - Metabolic Health
30203 - Molecular Targets and Therapies
30202 - Environmental Health
Forschungsfeld(er) Helmholtz Diabetes Center
Enabling and Novel Technologies
Genetics and Epidemiology
PSP-Element(e) G-507200-001
G-502296-001
G-503000-001
G-502200-001
G-504091-002
A-631900-001
G-500692-001
G-506501-001
G-502390-001
G-505700-001
G-502300-001
G-502210-001
G-502294-001
G-500600-001
Förderungen Projekt DEAL
Uehara Memorial Foundation, Japan
Alexander von Humboldt-Stiftung, Germany
China Scholarship Council
Horizon Europe funding programme under the Marie Sklodowska-Curie Actions Doctoral Networks
German Federal Ministry of Education and Research
German Center for Diabetes Research (DZD) (MHdA)
DFG
Deutsches Zentrum fur Diabetesforschung (DZD)
National Overseas Scholarship from the Government of India
DOI 10.1038/s44318-025-00520-2
WOS ID 001541723800001
Scopus ID 105012256060
PubMed ID 40750702
Erfassungsdatum 2025-10-01
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