PloS one, 2011-04, Vol.6 (4), p.e18532-e18532
2011
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Details
- Autor(en) / Beteiligte
- Titel
- Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis
- Ist Teil von
- PloS one, 2011-04, Vol.6 (4), p.e18532-e18532
- Ort / Verlag
- United States: Public Library of Science
- Erscheinungsjahr
- 2011
- Quelle
- Free E-Journal (出版社公開部分のみ）
- Beschreibungen/Notizen
- 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.
- Sprache
- Englisch
- Identifikatoren
- ISSN: 1932-6203eISSN: 1932-6203DOI: 10.1371/journal.pone.0018532Titel-ID: cdi_plos_journals_1312182592
- Format
- –
- Schlagworte
- 3T3-L1 Cells, Accumulation, Adipocytes, Adipogenesis, Adipose tissue, Adipose Tissue - growth & development, Adipose Tissue - metabolism, Age, Aging, Aging - metabolism, Animals, Apoptosis, Base Sequence, Bioaccumulation, Biological effects, Biology, Body Composition, Body fat, Cancer, Cell culture, Cell cycle, Cell proliferation, Chromatin Immunoprecipitation, Chronic diseases, Chronic illnesses, Development and progression, Diabetes, Diabetes mellitus, Differentiation, DNA Primers, E2F protein, Gene expression, Genes, Glucose, Glutathione, Glutathione - metabolism, Homeostasis, Inhibition, Insulin, Insulin resistance, Kinases, Male, Medicine, Metabolism, Mice, Mice, Inbred C57BL, Obesity, Oxidative Stress, Phase transitions, Phosphorylation, Promoter Regions, Genetic, Retina, Retinoblastoma, Retinoblastoma protein, Reverse Transcriptase Polymerase Chain Reaction, Risk factors, Rodents, S phase, Transcription, Transcription (Genetics), Transcription factors, Type 2 diabetes