| First Author | Sampath H | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 12 | Pages | e51697 |
| PubMed ID | 23284747 | Mgi Jnum | J:195631 |
| Mgi Id | MGI:5484954 | Doi | 10.1371/journal.pone.0051697 |
| Citation | Sampath H, et al. (2012) 8-Oxoguanine DNA glycosylase (OGG1) deficiency increases susceptibility to obesity and metabolic dysfunction. PLoS One 7(12):e51697 |
| abstractText | Oxidative damage to DNA is mainly repaired via base excision repair, a pathway that is catalyzed by DNA glycosylases such as 8-oxoguanine DNA glycosylase (OGG1). While OGG1 has been implicated in maintaining genomic integrity and preventing tumorigenesis, we report a novel role for OGG1 in altering cellular and whole body energy homeostasis. OGG1-deficient (Ogg1(-/-)) mice have increased adiposity and hepatic steatosis following exposure to a high-fat diet (HFD), compared to wild-type (WT) animals. Ogg1(-/-) animals also have higher plasma insulin levels and impaired glucose tolerance upon HFD feeding, relative to WT counterparts. Analysis of energy expenditure revealed that HFD-fed Ogg1(-/-) mice have a higher resting VCO(2) and consequently, an increased respiratory quotient during the resting phase, indicating a preference for carbohydrate metabolism over fat oxidation in these mice. Additionally, microarray and quantitative PCR analyses revealed that key genes of fatty acid oxidation, including carnitine palmitoyl transferase-1, and the integral transcriptional co-activator Pgc-1alpha were significantly downregulated in Ogg1(-/-) livers. Multiple genes involved in TCA cycle metabolism were also significantly reduced in livers of Ogg1(-/-) mice. Furthermore, hepatic glycogen stores were diminished, and fasting plasma ketones were significantly reduced in Ogg1(-/-) mice. Collectively, these data indicate that OGG1 deficiency alters cellular substrate metabolism, favoring a fat sparing phenotype, that results in increased susceptibility to obesity and related pathologies in Ogg1(-/-) mice. |
