ESPEYB19 11. Obesity and Weight Regulation New findings in adipose tissue biology (5 abstracts)
11.6. Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce
Li Q , Hagberg CE , Cascales HS , Lang S , Hyvönen MT , Salehzadeh F , Chen P , Alexandersson I , Terezaki E , Harms MJ , Kutschke M , Arifen N , Krämer N , Aouadi M , Knibbe C , Boucher J , Thorell A & Spalding KL
Department of Cell and Molecular Biology, Karolinska Institutet, Stockholm, Sweden
kirsty.spalding@ki.se Nat Med 2021; 27(11): 1941–1953 doi: 10.1038/s41591-021-01501-8
Brief Summary: This study analysed adipocytes from obese and hyperinsulinemic adults. They demonstrate that obesity is associated with the induction of a cell cycle program in mature adipocytes, leading to so-called endoreplication, as a strategy to remain functionally active. Under hyperinsulinemic conditions, this program fails and leads to cell-cycle exit and premature senescence.
Adipose tissue expands either by generating new adipocytes from progenitor cells (hyperplasia), or by enlargement of preexisting adipocytes (hypertrophy). While hypertrophic adipose tissue is generally considered a metabolically beneficial, hyperplastic adipose tissue is associated with an increased risk to develop metabolic disease [1]. Here, the authors used RNA sequencing of mature adipocytes from obese and hyperinsulinemic adults to demonstrate that mature adipocytes, although considered post-mitotic, can re-enter cell cycle, and that this cell cycle progression correlated with obesity and hyperinsulinemia. However, the cells do not enter mitosis, but increase their DNA content, suggesting that these adipocytes undergo endoreplication, i.e. replicate their genome in the absence of cell division. Endoreplication in other cell types has been described as a program to enhance cellular DNA content to respond to an increased demand of cell size, protein biosynthesis, or nutrient storage. The authors therefore suggest that this might be a response mechanism in adipocytes to remain functionally active. Upon prolonged hyperinsulinemia, however, adipocytes undergo cellular senescence, which might contribute to adipose tissue inflammation.
This study is of general interest since it shows for the first time that terminally differentiated adipocytes can re-enter the cell cycle in order to cope with metabolic stress. It would be interesting to investigate whether blocking of cellular senescence or elimination of those senescent adipocytes would lead to an improved metabolic outcome in obesity.
Reference: 1. Arner, E. et al. Adipocyte turnover: Relevance to human adipose tissue morphology. Diabetes 59, 105�109 (2010).
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ESPE Yearbook of Paediatric Endocrinology
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