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Obesity and hyperinsulinemia drive adipocytes to activate a cell cycle program and senesce
- Li, Q. (author)
-
- Hagberg, C. E. (author)
- Karolinska Institutet
- Cascales, H. S. (author)
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- Hyvonen, M. T. (author)
- Salehzadeh, F. (author)
- Alexandersson, I. (author)
- Terezaki, E. (author)
- Harms, M. J. (author)
- Kutschke, M. (author)
- Arifen, N. (author)
- Aouadi, M. (author)
- Knibbe, C. (author)
- Spalding, K. L. (author)
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- (creator_code:org_t)
- 2021-10-04
- 2021
- English.
- In: Nature Medicine. - : Springer Science and Business Media LLC. - 1078-8956 .- 1546-170X. ; 27, s. 1941-1953
- Journal article (peer-reviewed)
Abstract
Subject headings
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- 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. Studies in mature human adipocytes demonstrate that obesity and hyperinsulinemia can induce reentry into the cell cycle and induce senescence.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine (hsv//eng)
Keyword
- adipose-tissue
- DNA-damage
- secretory phenotype
- oxidative stress
- histone h3
- endoreplication
- phosphorylation
- progression
- inhibition
- polyploidy
- Biochemistry & Molecular Biology
- Cell Biology
- Research & Experimental
- Medicine
Publication and Content Type
- ref (subject category)
- art (subject category)
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- Li, Q.
- Hagberg, C. E.
- Cascales, H. S.
- Lang, S.
- Hyvonen, M. T.
- Salehzadeh, F.
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- Chen, P.
- Alexandersson, I ...
- Terezaki, E.
- Harms, M. J.
- Kutschke, M.
- Arifen, N.
- Kramer, N.
- Aouadi, M.
- Knibbe, C.
- Boucher, Jeremie
- Thorell, A.
- Spalding, K. L.
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
- MEDICAL AND HEAL ...
- and Basic Medicine
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- Nature Medicine
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- University of Gothenburg
- Karolinska Institutet
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