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白色脂肪细胞中磷酸肌酸代谢受损会促进炎症反应。

Impaired phosphocreatine metabolism in white adipocytes promotes inflammation.

作者信息

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

机构信息

Department of Medicine (H7), Karolinska Institutet, Karolinska University Hospital Huddinge, Huddinge, Sweden.

CHU Clermont-Ferrand, Service d'endocrinologie, diabétologie et maladies métaboliques, Clermont-Ferrand, France.

出版信息

Nat Metab. 2022 Feb;4(2):190-202. doi: 10.1038/s42255-022-00525-9. Epub 2022 Feb 14.

DOI:10.1038/s42255-022-00525-9
PMID:35165448
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8885409/
Abstract

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.

摘要

肥胖状态下促进白色脂肪细胞功能紊乱的机制在很大程度上仍不清楚。在此，我们整合了临床队列中白色脂肪组织（WAT）的代谢组学和转录组学数据，发现肥胖状态下WAT中磷酸肌酸/肌酸比值升高，肌酸激酶-B的表达和活性降低。在人类体外模型和小鼠体内模型中，我们证明白色脂肪细胞中磷酸肌酸代谢的降低通过影响三磷酸腺苷/二磷酸腺苷水平来改变腺苷单磷酸激活的蛋白激酶活性，这与WAT米色化无关。这种紊乱促进了一种促炎状态，部分特征是趋化因子（C-C基序）配体2（CCL2）产生增加。这些数据表明，磷酸肌酸/肌酸系统将细胞能量穿梭与人类和小鼠白色脂肪细胞中的促炎反应联系起来。我们的研究结果为肥胖状态下驱动WAT炎症的机制提供了意想不到的观点，并可能为针对脂肪细胞功能障碍提供途径。

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