The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue.
The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue.
复制标题
DOI：
10.1038/s41598-018-33151-1
复制
发表时间：
2018-10-05
影响因子：
4.6
通讯作者：
Sampath H
中科院分区：
文献类型：
--
作者：
Komakula SSB;Tumova J;Kumaraswamy D;Burchat N;Vartanian V;Ye H;Dobrzyn A;Lloyd RS;Sampath H
肥胖和相关的代谢病理学代表了一个重要的公共卫生问题。肥胖与氧化应激增加有关，氧化应激会损害基因组和线粒体DNA。两个DNA池中氧化诱导的损伤通过碱基切除修复途径修复，由DNA糖基化酶如8-氧代鸟嘌呤DNA糖基化酶（OGG 1）启动。OGG 1的全局缺失和常见的OGG 1多态性使小鼠和人类易患代谢性疾病。然而，线粒体OGG 1对这种代谢表型的相对贡献是未知的。在这里，我们证明转基因靶向OGG 1线粒体赋予显着的保护，从饮食诱导的肥胖，胰岛素抵抗和脂肪组织炎症。这些有利的代谢表型由特定代谢适应驱动的全身能量消耗增加介导，包括OGG 1转基因（Ogg 1 Tg）动物白色脂肪组织中线粒体呼吸增加。这些数据证明了DNA修复蛋白在调节线粒体能量和全身能量平衡中的关键作用。
Obesity and related metabolic pathologies represent a significant public health concern. Obesity is associated with increased oxidative stress that damages genomic and mitochondrial DNA. Oxidatively-induced lesions in both DNA pools are repaired via the base-excision repair pathway, initiated by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). Global deletion of OGG1 and common OGG1 polymorphisms render mice and humans susceptible to metabolic disease. However, the relative contribution of mitochondrial OGG1 to this metabolic phenotype is unknown. Here, we demonstrate that transgenic targeting of OGG1 to mitochondria confers significant protection from diet-induced obesity, insulin resistance, and adipose tissue inflammation. These favorable metabolic phenotypes are mediated by an increase in whole body energy expenditure driven by specific metabolic adaptations, including increased mitochondrial respiration in white adipose tissue of OGG1 transgenic (Ogg1Tg) animals. These data demonstrate a critical role for a DNA repair protein in modulating mitochondrial energetics and whole-body energy balance.
登录
查看更多内容
影响因子：
7.3
作者：
Frasca D;Blomberg BB
通讯作者：
Blomberg BB
影响因子：
--
作者：
Cardozo-Pelaez, F;Cox, DP;Bolin, C
通讯作者：
Bolin, C
影响因子：
9.2
作者：
Lu, RZ;Nash, HM;Verdine, GL
通讯作者：
Verdine, GL
一种评估整个白色脂肪组织中线粒体生物能学的方法。
影响因子：
11.4
作者：
Dunham-Snary KJ;Sandel MW;Westbrook DG;Ballinger SW
通讯作者：
Ballinger SW
影响因子：
4
作者：
Busiello RA;Savarese S;Lombardi A
通讯作者：
Lombardi A