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Journal Articles Nature Medicine Year : 2021

Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce

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Qian Li
Carolina Hagberg
Mervi Hyvönen
Ping Chen
Ida Alexandersson
Eleni Terezaki
Myriam Aouadi
Jeremie Boucher
  • Function : Author
  • PersonId : 787791
  • IdRef : 118621866
Kirsty Spalding

Abstract

Obesity is considered an important factor for many chronic diseases, including diabetes, cardiovascular disease and cancer. The expansion of adipose tissue in obesity is due to an increase in both adipocyte progenitor differentiation and mature adipocyte cell size. Adipocytes, however, are thought to be unable to divide or enter the cell cycle. We demonstrate that mature human adipocytes unexpectedly display a gene and protein signature indicative of an active cell cycle program. Adipocyte cell cycle progression associates with obesity and hyperinsulinemia, with a concomitant increase in cell size, nuclear size and nuclear DNA content. Chronic hyperinsulinemia in vitro or in humans, however, is associated with subsequent cell cycle exit, leading to a premature senescent transcriptomic and secretory profile in adipocytes. Premature senescence is rapidly becoming recognized as an important mediator of stress-induced tissue dysfunction. By demonstrating that adipocytes can activate a cell cycle program, we define a mechanism whereby mature human adipocytes senesce. We further show that by targeting the adipocyte cell cycle program using metformin, it is possible to influence adipocyte senescence and obesity-associated adipose tissue inflammation.
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Dates and versions

hal-03479060 , version 1 (14-12-2021)

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Qian Li, Carolina Hagberg, Helena Silva Cascales, Shuai Lang, Mervi Hyvönen, et al.. Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce. Nature Medicine, 2021, 27 (11), pp.1941-1953. ⟨10.1038/s41591-021-01501-8⟩. ⟨hal-03479060⟩
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