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.
Highlights
Aging is a complex process due to the interaction of genetic, epigenetic, environmental and stochastic factors throughout life, which usually comes together with an accumulation of visceral fat, causing obesity [1,2,3]
We aimed to study the potential differences in the mRNA expression pattern of several cell cycle regulators among the three different adipose tissue depots in young computed tomography (CT) mice
We characterized the differential expression of several cell cycle regulators (p27, cdk2, ccna and ccne) between the different fat depots, as well as their regulation during aging and obesity and their potential implications in these physiological/pathophysiological situations
Summary
Aging is a complex process due to the interaction of genetic, epigenetic, environmental and stochastic factors throughout life, which usually comes together with an accumulation of visceral fat, causing obesity [1,2,3]. The subcutaneous WAT (scWAT) is found under the skin, where it functions as a protective and isolating barrier to avoid heat loss, whereas visceral WAT (vWAT) is localized surrounding vital organs in the peritoneum and rib cage [9]. Despite both being white fat, they are heterogeneous and their implication in the metabolic complications caused by obesity is different. Triglycerides can ectopically deposit in the liver, muscle and heart This ectopic accumulation facilitates alterations in organs where fat is accumulated, causing lipotoxicity and fostering the development of pathologies such as insulin resistance and type 2 diabetes mellitus (DM), among others [1]
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