Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.
Oxidative stress accumulates in adipose tissue during aging and inhibits adipogenesis.
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DOI：
10.1371/journal.pone.0018532
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发表时间：
2011-04-14
期刊：
影响因子：
3.7
通讯作者：
Bruemmer D
中科院分区：
文献类型：
--
作者：
Findeisen HM;Pearson KJ;Gizard F;Zhao Y;Qing H;Jones KL;Cohn D;Heywood EB;de Cabo R;Bruemmer D
衰老是2型糖尿病发展的主要独立危险因素，并伴有胰岛素抵抗和脂肪组织功能障碍。与衰老和与年龄相关的慢性疾病隐含相关的最重要因素之一是氧化应激的积累。然而，氧化应激增加对脂肪组织生物学的影响仍然难以捉摸。在这项研究中，我们证明了小鼠的衰老导致脂肪量的减少和脂肪组织中氧化应激的积累。在体外，通过谷胱甘肽耗竭增加氧化应激抑制前脂肪细胞分化。这种对脂肪形成的抑制至少部分是由于在脂肪细胞分化过程的初始有丝分裂克隆扩增期间细胞增殖减少和G1→ S-期转变的抑制。虽然视网膜母细胞瘤蛋白（Rb）的磷酸化细胞周期蛋白/cdk复合物保持不受影响，氧化应激减少Rb下游的S期基因的表达。这种由增加的氧化应激引起的S期基因表达的沉默是通过涉及抑制E2 F募集和其靶启动子反式激活的转录机制介导的。总的来说，这些数据证明了以前未被认识到的氧化应激在调节脂肪生成中的作用，这可能有助于与年龄相关的脂肪组织功能障碍。
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 G1→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.
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影响因子：
7.7
作者：
DEFRONZO, RA
通讯作者：
DEFRONZO, RA
DOI：
10.1152/ajpregu.2001.280.6.r1772
发表时间：
2001-06-01
影响因子：
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120.7
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影响因子：
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作者：
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DOI：
10.1098/rstb.2005.1770
发表时间：
2005-12-29
影响因子：
6.3
作者：
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通讯作者：
Dröge, W