The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue

被引：59

作者：

Komakula, Sai Santosh Babu ^{[1
,2
,3
]}

Tumova, Jana ^{[1
,2
]}

Kumaraswamy, Deeptha ^{[1
,2
]}

Burchat, Natalie ^{[1
,2
]}

Vartanian, Vladimir ^{[4
]}

Ye, Hong ^{[1
,2
]}

Dobrzyn, Agnieszka ^{[3
]}

Lloyd, R. Stephen ^{[4
]}

Sampath, Harini ^{[1
,2
]}

机构：

[1] Rutgers State Univ, New Jersey Inst Food Nutr & Hlth, Dept Nutr Sci, New Brunswick, NJ 08901 USA

[2] Rutgers State Univ, New Jersey Inst Food Nutr & Hlth, Rutgers Ctr Lipid Res, New Brunswick, NJ 08901 USA

[3] Nencki Inst Expt Biol, Lab Cell Signaling & Metab Disorders, Warsaw, Poland

[4] Oregon Hlth & Sci Univ, Dept Mol & Med Genet, Oregon Inst Occupat Hlth Sci, Portland, OR 97239 USA

来源：

SCIENTIFIC REPORTS | 2018年 / 8卷

基金：

欧盟地平线“2020”;

关键词：

GLYCOSYLASE; 1; OGG1; OXIDATIVE DAMAGE; 8-OXOGUANINE GLYCOSYLASE; SER326CYS POLYMORPHISM; GENE-EXPRESSION; CELLS; APOPTOSIS; HOGG1; LUNG; PALMITATE;

D O I：

10.1038/s41598-018-33151-1

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

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 (Ogg1(Tg)) animals. These data demonstrate a critical role for a DNA repair protein in modulating mitochondrial energetics and whole-body energy balance.

引用

页数：15

共 69 条

[61] Oxidative damage to methyl-CpG sequences inhibits the binding of the methyl-CpG binding domain (MBD) of methyl-CpG binding protein 2 (MeCP2) [J].