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Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence

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Item Type:Article
Title:Impaired Plakophilin-2 in obesity breaks cell cycle dynamics to breed adipocyte senescence
Creators Name:Lluch, A. and Latorre, J. and Serena-Maione, A. and Espadas, I. and Caballano-Infantes, E. and Moreno-Navarrete, J.M. and Oliveras-Cañellas, N. and Ricart, W. and Malagón, M.M. and Martin-Montalvo, A. and Birchmeier, W. and Szymanski, W. and Graumann, J. and Gómez-Serrano, M. and Sommariva, E. and Fernández-Real, J.M. and Ortega, F.J.
Abstract:Plakophilin-2 (PKP2) is a key component of desmosomes, which, when defective, is known to promote the fibro-fatty infiltration of heart muscle. Less attention has been given to its role in adipose tissue. We report here that levels of PKP2 steadily increase during fat cell differentiation, and are compromised if adipocytes are exposed to a pro-inflammatory milieu. Accordingly, expression of PKP2 in subcutaneous adipose tissue diminishes in patients with obesity, and normalizes upon mild-to-intense weight loss. We further show defective PKP2 in adipocytes to break cell cycle dynamics and yield premature senescence, a key rheostat for stress-induced adipose tissue dysfunction. Conversely, restoring PKP2 in inflamed adipocytes rewires E2F signaling towards the re-activation of cell cycle and decreased senescence. Our findings connect the expression of PKP2 in fat cells to the physiopathology of obesity, as well as uncover a previously unknown defect in cell cycle and adipocyte senescence due to impaired PKP2.
Keywords:Mechanisms of Disease, Obesity
Source:Nature Communications
Publisher:Nature Publishing Group
Page Range:5106
Date:22 August 2023
Official Publication:https://doi.org/10.1038/s41467-023-40596-0
PubMed:View item in PubMed

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