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

Abstract

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.

Keywords: CDK2; adipose tissue; aging; cell cycle; cyclins; obesity; p27.

Figure 1

Changes in adipose tissue mass induced by aging and obesity in female mice. (A) Whole body fat mass measured by magnetic resonance technology in non-fasted mice fed a control diet (CT) at 2 (young CT), 6 (adult CT) and 18 (aged CT) months of age or aged under a HFD up to 18-month-old (aged DIO); (B): weights of the different adipose tissue depots in CT mice (young, adult, and aged) and in aged DIO mice after an overnight fasting. Data are expressed as mean ± SEM. ** p < 0.01, *** p < 0.001 vs. young CT mice; ^### p < 0.001 vs. aged CT mice (n = 7–9).

Figure 2

Differential adipose depot expression of p27 (A,E), cdk2 (B,F), ccna (C,G), ccne (D,H), between gWAT, scWAT and iBAT in young CT mice (2-month-old) and aged CT female mice (18-month-old). Data (mean ± SEM) are expressed as fold change of gWAT, considered as 1. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. gWAT; ^# p < 0.05, ^### p < 0.001 vs. scWAT (n = 5–8).

Figure 3

Changes induced by aging on the mRNA expression of p27 (A); cdk2 (B); ccna (C); ccne (D) within gWAT, scWAT and iBAT from young, adult and aged (2-, 6- and 18-month-old) CT female mice. Data (mean ± SEM) are expressed as fold change of Young CT, considered as 1. * p < 0.05, ** p < 0.01, *** p < 0.001 vs. young CT; ^# p < 0.05 vs. adult CT; ^t p = 0.07 vs. Young CT (n = 5–8).

Figure 4

Effect of diet-induced obesity (DIO) on the expression of p27 (A), cdk2 (B), ccna (C), and ccne (D) in gWAT, scWAT and iBAT from aged (18-month-old) female mice. Data (mean ± SEM) are expressed as fold change of Aged CT gWAT considered as 1. * p < 0.05 vs. aged CT mice (n = 5–9).

Figure 5

(A,B): Differential mRNA expression of p27 and CDK2 in human vWAT vs. scWAT. Data (mean ± SEM) are expressed as fold change of vWAT considered as 1. ** p < 0.01 vs. vWAT. (C,D). Effects of overweight and obesity with or without type 2 DM on the mRNA expression of p27 (C) and CDK2 (D) in human vWAT and scWAT. Data (mean ± SEM) are expressed as fold change of normal-weight group, considered as 1. * p < 0.05, vs. normal-weight.