4.7 Article

Regulation of p27 and Cdk2 Expression in Different Adipose Tissue Depots in Aging and Obesity

Journal

Publisher

MDPI
DOI: 10.3390/ijms222111745

Keywords

aging; obesity; cell cycle; p27; CDK2; cyclins; adipose tissue

Funding

  1. Navarra Government-Centros Tecnologicos [0011-1383-2019-000005 (PC056-057)]
  2. MINECO/FEDER [BFU2015-65937-R]
  3. CIBER Physiopathology of Obesity and Nutrition (CIBERobn), Carlos III Health Research Institute [CB12/03/30002]
  4. Catalan Government through ACCIO-Eurecat
  5. Centre for the Development of Industrial Technology (CDTI) of the Spanish Ministry of Science and Innovation under the grant agreement TECNOMIFOOD project [CER-20191010]
  6. Juan de la Cierva grant [IJCI-2016-30025]
  7. Center for Nutrition Research (University of Navarra)

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Aging is often associated with increased fat accumulation and related comorbidities, with differences observed in the expression of p27 and cdk2 in different adipose tissue depots during aging and obesity. These findings suggest that p27 and cdk2 may contribute to metabolic differences in adipose tissue depots.
Aging usually comes associated with increased visceral fat accumulation, reaching even an obesity state, and favoring its associated comorbidities. One of the processes involved in aging is cellular senescence, which is highly dependent on the activity of the regulators of the cell cycle. The aim of this study was to analyze the changes in the expression of p27 and cdk2 in different adipose tissue depots during aging, as well as their regulation by obesity in mice. Changes in the expression of p27 and CDK2 in visceral and subcutaneous white adipose tissue (WAT) biopsies were also analyzed in a human cohort of obesity and type 2 diabetes. p27, but not cdk2, exhibits a lower expression in subcutaneous than in visceral WAT in mice and humans. p27 is drastically downregulated by aging in subcutaneous WAT (scWAT), but not in gonadal WAT, of female mice. Obesity upregulates p27 and cdk2 expression in scWAT, but not in other fat depots of aged mice. In humans, a significant upregulation of p27 was observed in visceral WAT of subjects with obesity. Taken together, these results show a differential adipose depot-dependent regulation of p27 and cdk2 in aging and obesity, suggesting that p27 and cdk2 could contribute to the adipose-tissue depot's metabolic differences. Further studies are necessary to fully corroborate this hypothesis.

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