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Maqdasy, S.* ; Lecoutre, S.* ; Renzi, G.* ; Frendo-Cumbo, S.* ; Rizo-Roca, D.* ; Moritz, T.* ; Juvany, M.* ; Hodek, O.* ; Gao, H.* ; Couchet, M.* ; Witting, M. ; Kerr, A.* ; Bergo, M.O.* ; Choudhury, R.P.* ; Aouadi, M.* ; Zierath, J.R.* ; Krook, A.* ; Mejhert, N.* ; Rydén, M.*

Impaired phosphocreatine metabolism in white adipocytes promotes inflammation.

Nat. Metab. 4, 190-202 (2022)
Publ. Version/Full Text Research data DOI PMC
Open Access Gold (Paid Option)
Creative Commons Lizenzvertrag
The mechanisms promoting disturbed white adipocyte function in obesity remain largely unclear. Herein, we integrate white adipose tissue (WAT) metabolomic and transcriptomic data from clinical cohorts and find that the WAT phosphocreatine/creatine ratio is increased and creatine kinase-B expression and activity is decreased in the obese state. In human in vitro and murine in vivo models, we demonstrate that decreased phosphocreatine metabolism in white adipocytes alters adenosine monophosphate-activated protein kinase activity via effects on adenosine triphosphate/adenosine diphosphate levels, independently of WAT beigeing. This disturbance promotes a pro-inflammatory profile characterized, in part, by increased chemokine (C-C motif) ligand 2 (CCL2) production. These data suggest that the phosphocreatine/creatine system links cellular energy shuttling with pro-inflammatory responses in human and murine white adipocytes. Our findings provide unexpected perspectives on the mechanisms driving WAT inflammation in obesity and may present avenues to target adipocyte dysfunction.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Activated Protein-kinase; Adipose-tissue; Creatine-kinase; Obesity; Ampk; Expression; Thermogenesis; Transport; Health; Target
ISSN (print) / ISBN 2522-5812
e-ISSN 2522-5812
Journal Nature metabolism
Quellenangaben Volume: 4, Issue: 2, Pages: 190-202 Article Number: , Supplement: ,
Publisher Springer
Publishing Place London
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Research Unit Analytical BioGeoChemistry (BGC)
Grants Margareta af Uggla's foundation
Swedish Research Council, KI infrastructure and Centre for Innovative Medicine
Novo Nordisk
Fondation Bettencourt Schueller
Societe Francophone du Diabete
Universite Clermont Auvergne
Strategic Research Programme in Diabetes at Karolinska Institutet
Stockholm County Council
Swedish Diabetes Foundation
Knut and Alice Wallenbergs Foundation
NovoNordisk Foundation
ERC-SyG SPHERES
Swedish Research Council
CIMED