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Klingelhuber, F. ; Frendo-Cumbo, S.* ; Omar-Hmeadi, M.* ; Massier, L.* ; Kakimoto, P. ; Taylor, A.J. ; Couchet, M.* ; Ribicic, S. ; Wabitsch, M.* ; Messias, A.C. ; Iuso, A. ; Müller, T.D. ; Rydén, M.* ; Mejhert, N.* ; Krahmer, N.

A spatiotemporal proteomic map of human adipogenesis.

Nat. Metab., DOI: 10.1038/s42255-024-01025-8 (2024)
Publ. Version/Full Text DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
White adipocytes function as major energy reservoirs in humans by storing substantial amounts of triglycerides, and their dysfunction is associated with metabolic disorders; however, the mechanisms underlying cellular specialization during adipogenesis remain unknown. Here, we generate a spatiotemporal proteomic atlas of human adipogenesis, which elucidates cellular remodelling as well as the spatial reorganization of metabolic pathways to optimize cells for lipid accumulation and highlights the coordinated regulation of protein localization and abundance during adipocyte formation. We identify compartment-specific regulation of protein levels and localization changes of metabolic enzymes to reprogramme branched-chain amino acids and one-carbon metabolism to provide building blocks and reduction equivalents. Additionally, we identify C19orf12 as a differentiation-induced adipocyte lipid droplet protein that interacts with the translocase of the outer membrane complex of lipid droplet-associated mitochondria and regulates adipocyte lipid storage by determining the capacity of mitochondria to metabolize fatty acids. Overall, our study provides a comprehensive resource for understanding human adipogenesis and for future discoveries in the field.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Adipose Triglyceride Lipase; Protein; Dynamics; Localization; Number; Link
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Journal Nature metabolism
Publisher Springer
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Obesity (IDO)
Institute of Structural Biology (STB)
Institute of Neurogenomics (ING)
Grants Swedish Society for Medical Research
European Foundation for the Study of Diabetes (Future Leader Award)
Swedish Research Council
ERC-SyG SPHERES
Novo Nordisk Foundation
MeRIAD consortium
Knut and Alice Wallenbergs Foundation
Centre for Innovative Medicine
Helmholtz Zentrum Munchen - Deutsches Forschungszentrum fur Gesundheit und Umwelt (GmbH)
Swedish Diabetes Foundation
Stockholm County Council
Strategic Research Programme in Diabetes at the Karolinska Institutet
DFG BATenergy
NBIA Suisse
Hoffnungsbaum
NBIA Disorders Association
NBIA Poland
German Centre for Diabetes Research
German Research Foundation
European Research Council (ERC-CoG )
Karolinska Institutet
DFG Emmy Noether
Novo Nordisk postdoctoral fellowship