Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.
Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. How...
| Main Authors: | , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2011-04-01
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| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3077372?pdf=render |
| _version_ | 1818321527986192384 |
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| author | Hannes M Findeisen Kevin J Pearson Florence Gizard Yue Zhao Hua Qing Karrie L Jones Dianne Cohn Elizabeth B Heywood Rafael de Cabo Dennis Bruemmer |
| author_facet | Hannes M Findeisen Kevin J Pearson Florence Gizard Yue Zhao Hua Qing Karrie L Jones Dianne Cohn Elizabeth B Heywood Rafael de Cabo Dennis Bruemmer |
| author_sort | Hannes M Findeisen |
| collection | DOAJ |
| description | Aging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction. |
| first_indexed | 2024-12-13T10:42:20Z |
| format | Article |
| id | doaj.art-f55bcfc0697341f98d6bbae288525dad |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-13T10:42:20Z |
| publishDate | 2011-04-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-f55bcfc0697341f98d6bbae288525dad2022-12-21T23:50:26ZengPublic Library of Science (PLoS)PLoS ONE1932-62032011-04-0164e1853210.1371/journal.pone.0018532Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.Hannes M FindeisenKevin J PearsonFlorence GizardYue ZhaoHua QingKarrie L JonesDianne CohnElizabeth B HeywoodRafael de CaboDennis BruemmerAging constitutes a major independent risk factor for the development of type 2 diabetes and is accompanied by insulin resistance and adipose tissue dysfunction. One of the most important factors implicitly linked to aging and age-related chronic diseases is the accumulation of oxidative stress. However, the effect of increased oxidative stress on adipose tissue biology remains elusive. In this study, we demonstrate that aging in mice results in a loss of fat mass and the accumulation of oxidative stress in adipose tissue. In vitro, increased oxidative stress through glutathione depletion inhibits preadipocyte differentiation. This inhibition of adipogenesis is at least in part the result of reduced cell proliferation and an inhibition of G(1)→S-phase transition during the initial mitotic clonal expansion of the adipocyte differentiation process. While phosphorylation of the retinoblastoma protein (Rb) by cyclin/cdk complexes remains unaffected, oxidative stress decreases the expression of S-phase genes downstream of Rb. This silencing of S phase gene expression by increased oxidative stress is mediated through a transcriptional mechanism involving the inhibition of E2F recruitment and transactivation of its target promoters. Collectively, these data demonstrate a previously unrecognized role of oxidative stress in the regulation of adipogenesis which may contribute to age-associated adipose tissue dysfunction.http://europepmc.org/articles/PMC3077372?pdf=render |
| spellingShingle | Hannes M Findeisen Kevin J Pearson Florence Gizard Yue Zhao Hua Qing Karrie L Jones Dianne Cohn Elizabeth B Heywood Rafael de Cabo Dennis Bruemmer Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis. PLoS ONE |
| title | Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis. |
| title_full | Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis. |
| title_fullStr | Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis. |
| title_full_unstemmed | Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis. |
| title_short | Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis. |
| title_sort | oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis |
| url | http://europepmc.org/articles/PMC3077372?pdf=render |
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