Skip to main content
SLU publication database (SLUpub)

Research article2022Peer reviewedOpen access

Impaired phosphocreatine metabolism in white adipocytes promotes inflammation

Maqdasy, Salwan; Lecoutre, Simon; Renzi, Gianluca; Frendo-Cumbo, Scott; Rizo-Roca, David; Moritz, Thomas; Juvany, Marta; Hodek, Ondrej; Gao, Hui; Couchet, Morgane; Witting, Michael; Kerr, Alastair; Bergo, Martin O.; Choudhury, Robin P.; Aouadi, Myriam; Zierath, Juleen R.; Krook, Anna; Mejhert, Niklas; Ryden, Mikael

Abstract

Maqdasy, Lecoutre et al. show that increased an phosphocreatine/creatine ratio in white adipocytes drives changes in AMP-activated protein kinase activity and promotes white adipocyte inflammation during obesity.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.

Published in

Nature Metabolism
2022, Volume: 4, number: 2, pages: 190-202
Publisher: NATURE PORTFOLIO