8-Oxoguanine DNA Glycosylase (OGG1) Deficiency Increases Susceptibility to Obesity and Metabolic Dysfunction

• DOI: 10.1371/journal.pone.0051697
• Publication Date: 2012-12-17T21:57:16Z
• Authors: Harini Sampath; Vladimir Vartanian; M. Rick Rollins; Kunihiko Sakumi; Yusaku Nakabeppu; R. Stephen Lloyd
• Keywords: Steatosis

Oxidative damage to DNA is mainly repaired via base excision repair, a pathway that catalyzed by glycosylases such as 8-oxoguanine glycosylase (OGG1). While OGG1 has been implicated in maintaining genomic integrity and preventing tumorigenesis, we report novel role for altering cellular whole body energy homeostasis. OGG1-deficient (Ogg1(-/-)) mice have increased adiposity hepatic steatosis following exposure high-fat diet (HFD), compared wild-type (WT) animals. Ogg1(-/-) animals also higher plasma insulin levels impaired glucose tolerance upon HFD feeding, relative WT counterparts. Analysis of expenditure revealed HFD-fed resting VCO(2) consequently, an respiratory quotient during the phase, indicating preference carbohydrate metabolism over fat oxidation these mice. Additionally, microarray quantitative PCR analyses key genes fatty acid oxidation, including carnitine palmitoyl transferase-1, integral transcriptional co-activator Pgc-1α were significantly downregulated livers. Multiple involved TCA cycle reduced livers Furthermore, glycogen stores diminished, fasting ketones Collectively, data indicate deficiency alters substrate metabolism, favoring sparing phenotype, results susceptibility obesity related pathologies