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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 Hybrid
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
Keywords Activated Protein-kinase; Adipose-tissue; Creatine-kinase; Obesity; Ampk; Expression; Thermogenesis; Transport; Health; Target
Language english
Publication Year 2022
HGF-reported in Year 2022
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
Reviewing status Peer reviewed
Institute(s) CF Metabolomics & Proteomics (CF-MPC)
Research Unit BioGeoChemistry and Analytics (BGC)
POF-Topic(s) 30203 - Molecular Targets and Therapies
30202 - Environmental Health
Research field(s) Enabling and Novel Technologies
Environmental Sciences
PSP Element(s) G-505700-001
G-504800-001
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
DOI 10.1038/s42255-022-00525-9
WOS ID WOS:000754940600001
Scopus ID 85124732151
PubMed ID 35165448
Erfassungsdatum 2022-05-04
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