TY - JOUR
T1 - The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue
AU - Komakula, Sai Santosh Babu
AU - Tumova, Jana
AU - Kumaraswamy, Deeptha
AU - Burchat, Natalie
AU - Vartanian, Vladimir
AU - Ye, Hong
AU - Dobrzyn, Agnieszka
AU - Lloyd, R. Stephen
AU - Sampath, Harini
N1 - Publisher Copyright:
© 2018, The Author(s).
PY - 2018/12/1
Y1 - 2018/12/1
N2 - 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.
AB - 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.
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U2 - 10.1038/s41598-018-33151-1
DO - 10.1038/s41598-018-33151-1
M3 - Article
C2 - 30291284
AN - SCOPUS:85054466760
SN - 2045-2322
VL - 8
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 14886
ER -