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

Sai Santosh Babu Komakula, Jana Tumova, Deeptha Kumaraswamy, Natalie Burchat, Vladimir Vartanian, Hong Ye, Agnieszka Dobrzyn, Robert (Stephen) Lloyd, Harini Sampath

Research output: Contribution to journalArticle

5 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Article number14886
JournalScientific Reports
Volume8
Issue number1
DOIs
StatePublished - Dec 1 2018

Fingerprint

White Adipose Tissue
DNA Repair
DNA Glycosylases
Obesity
Phenotype
Genetically Modified Animals
Proteins
Metabolic Diseases
Mitochondrial DNA
Energy Metabolism
Insulin Resistance
Adipose Tissue
Mitochondria
Respiration
Oxidative Stress
Public Health
Pathology
Diet
Inflammation
DNA

ASJC Scopus subject areas

  • General

Cite this

Komakula, S. S. B., Tumova, J., Kumaraswamy, D., Burchat, N., Vartanian, V., Ye, H., ... Sampath, H. (2018). The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue. Scientific Reports, 8(1), [14886]. https://doi.org/10.1038/s41598-018-33151-1

The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue. / Komakula, Sai Santosh Babu; Tumova, Jana; Kumaraswamy, Deeptha; Burchat, Natalie; Vartanian, Vladimir; Ye, Hong; Dobrzyn, Agnieszka; Lloyd, Robert (Stephen); Sampath, Harini.

In: Scientific Reports, Vol. 8, No. 1, 14886, 01.12.2018.

Research output: Contribution to journalArticle

Komakula, SSB, Tumova, J, Kumaraswamy, D, Burchat, N, Vartanian, V, Ye, H, Dobrzyn, A, Lloyd, RS & Sampath, H 2018, 'The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue', Scientific Reports, vol. 8, no. 1, 14886. https://doi.org/10.1038/s41598-018-33151-1
Komakula, Sai Santosh Babu ; Tumova, Jana ; Kumaraswamy, Deeptha ; Burchat, Natalie ; Vartanian, Vladimir ; Ye, Hong ; Dobrzyn, Agnieszka ; Lloyd, Robert (Stephen) ; Sampath, Harini. / The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue. In: Scientific Reports. 2018 ; Vol. 8, No. 1.
@article{08493abb71214177a3eae49ad3224ce0,
title = "The DNA Repair Protein OGG1 Protects Against Obesity by Altering Mitochondrial Energetics in White Adipose Tissue",
abstract = "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.",
author = "Komakula, {Sai Santosh Babu} and Jana Tumova and Deeptha Kumaraswamy and Natalie Burchat and Vladimir Vartanian and Hong Ye and Agnieszka Dobrzyn and Lloyd, {Robert (Stephen)} and Harini Sampath",
year = "2018",
month = "12",
day = "1",
doi = "10.1038/s41598-018-33151-1",
language = "English (US)",
volume = "8",
journal = "Scientific Reports",
issn = "2045-2322",
publisher = "Nature Publishing Group",
number = "1",

}

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, Robert (Stephen)

AU - Sampath, Harini

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.

UR - http://www.scopus.com/inward/record.url?scp=85054466760&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85054466760&partnerID=8YFLogxK

U2 - 10.1038/s41598-018-33151-1

DO - 10.1038/s41598-018-33151-1

M3 - Article

VL - 8

JO - Scientific Reports

JF - Scientific Reports

SN - 2045-2322

IS - 1

M1 - 14886

ER -