Impaired phosphocreatine metabolism in white adipocytes promotes inflammation
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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; Rydén, Mikael.
In: Nature Metabolism, Vol. 4, 2022, p. 190-202.Research output: Contribution to journal › Journal article › Research › peer-review
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TY - JOUR
T1 - Impaired phosphocreatine metabolism in white adipocytes promotes inflammation
AU - Maqdasy, Salwan
AU - Lecoutre, Simon
AU - Renzi, Gianluca
AU - Frendo-Cumbo, Scott
AU - Rizo-Roca, David
AU - Moritz, Thomas
AU - Juvany, Marta
AU - Hodek, Ondrej
AU - Gao, Hui
AU - Couchet, Morgane
AU - Witting, Michael
AU - Kerr, Alastair
AU - Bergo, Martin O.
AU - Choudhury, Robin P.
AU - Aouadi, Myriam
AU - Zierath, Juleen R.
AU - Krook, Anna
AU - Mejhert, Niklas
AU - Rydén, Mikael
N1 - Publisher Copyright: © 2022, The Author(s).
PY - 2022
Y1 - 2022
N2 - 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.
AB - 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.
U2 - 10.1038/s42255-022-00525-9
DO - 10.1038/s42255-022-00525-9
M3 - Journal article
C2 - 35165448
AN - SCOPUS:85124732151
VL - 4
SP - 190
EP - 202
JO - Nature Metabolism
JF - Nature Metabolism
SN - 2522-5812
ER -
ID: 298646001