The novelty of our current work is that we demonstrated: (1) HFD-induced insulin resistance is primarily due to defects in hepatic insulin action in Ogg1-KO mice and (2) reconstitution of the hOGG1 enzyme specifically in mitochondria of Ogg1-KO animals not only prevented oxidative mtDNA damage but also coordinated the protection from HFD-induced insulin resistance. Here, OGG1 is linked to Insulin resistance.