Oxidative stress is implicated in the pathogenesis of cancer, neurodegeneration and aging. hMTH1 is a hydrolase able to protect cells by oxidative damage. Overexpression of hMTH1 in transgenic mice (hMTH1‐Tg) confers significant protection against neurodegeneration and motor impairment. In this study, we use the hMTH1‐Tg mouse model and we found that oxidative damage is able to affect brain metabolism and adipose organ composition and extension. Moreover, we investigated the protective role of hMTH1-tg against an environmental oxidative stimulus like the assumption of a diet at high content of fat.