MassIVE MSV000091898

Partial Public PXD042110

Loss of the armadillo-repeat protein Plakophilin 2 in obesity breaks cell cycle dynamics to breed adipocyte senescence

Description

Plakophilin2 (PKP2) is a key component of desmosomes mostly recognized for its involvement in the fibro fatty infiltration of heart muscle under defective PKP2. While thoroughly explored in cardiomyocytes, less attention has been given to its role in fat cells. Here we report steadily increased PKP2 during adipogenesis, with expression levels reaching its apex in terminally differentiated adipocytes. Notably, the loss of this protein in adipocytes under a pro-inflammatory microenvironment demonstrates its commitment in maintaining the expression of genes required to nurture cell cycle. Then, we show that diminished expressions of this member of the armadillo repeat family in subcutaneous adipose tissue co-segregate with obesity, being normalized upon mild to intense weight loss. We also demonstrate that impaired PKP2 in human adipocytes breaks cell cycle dynamics to breed premature senescence, a key rheostat for stress induced adipose tissue dysfunction. Conversely, restoring PKP2 in inflamed adipocytes rewires E2F signalling towards re-activation of cell cycle and decreased senescence. Our findings bound the expression of PKP2 in fat cells to the physiopathology of obesity, and uncover a previously unknown defect in cell cycle and activated adipocyte senescence due to impaired PKP2. [doi:10.25345/C55M62H7G] [dataset license: CC0 1.0 Universal (CC0 1.0)]

Keywords: Plakophilin-2, adipose tissue, adipocytes, senescence, inflammation, obesity

Contact

Principal Investigators:
(in alphabetical order)
Francisco Ortega, Institut d Investigacio Biomedica de Girona, Spain
Submitting User: Wszymanski
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