Deficiency of glutathione peroxidase-1 and catalase attenuated diet-induced obesity and associated metabolic disorders.

Oxidative stress has been considered to contribute to the development of obesity-related metabolic disorders including insulin resistance. To the contrary, deficiency of an anti-oxidizing enzyme, glutathione peroxidase (GPx)-1, was reported to enhance insulin signaling, suggesting that oxidative stress may inhibit the development of type 2 diabetes. However, the beneficial effects of the absence of GPx-1 in metabolic homeostasis, including body weight control, have not yet been clearly manifested. To clarify the relationship between oxidative stress and obesity-related metabolic disorders, we investigated another mouse deficient with both GPx-1 and catalase (Cat).

C57BL/6J wild-type and GPx-1^-/- × Cat^-/- mice were fed with a high-fat diet (60% fat) or a normal chow diet for 16 weeks and were investigated for metabolic and histological studies.

Body weight gain was significantly reduced, and glucose metabolism as well as hepatic steatosis was obviously improved in the GPx-1^-/- × Cat^-/- mice. The serum levels of insulin and total cholesterol were also significantly lowered. For the underlying mechanism, inflammation was attenuated and expression of markers for fat browning was enhanced in the visceral white adipose tissues.

Oxidative stress due to deficiency of GPx-1 and Cat may improve obesity-related metabolic disorders through attenuation of inflammation and fat browning.