Short-term vitamin E treatment impairs reactive oxygen species signaling required for adipose tissue expansion, resulting in fatty liver and insulin resistance in obese mice

ObjectivesThe use of antioxidant therapy in the treatment of oxidative stress-related diseases such as cardiovascular disease, diabetes or obesity remains controversial. Our aim is to demonstrate that antioxidant supplementation may promote negative effects if used before the establishment of oxidative stress due to a reduced ROS generation under physiological levels, in a mice model of obesity.MethodsC57BL/6J mice were fed with a high-fat diet for 14 weeks, with (OE group) or without (O group) vitamin E supplementation.ResultsO mice developed a mild degree of obesity, which was not enough to induce metabolic alterations or oxidative stress. These animals exhibited a healthy expansion of retroperitoneal white adipose tissue (rpWAT) and the liver showed no signs of lipotoxicity. Interestingly, despite achieving a similar body weight, OE mice were insulin resistant. In the rpWAT they presented a reduced generation of ROS, even below physiological levels (C: 1651.0 ± 212.0; O: 3113 ± 284.7; OE: 917.6 ±104.4 RFU/mg protein. C vs OE pConclusionsThis study provides in vivo evidence for the role of ROS as second messengers in adipogenesis, lipid metabolism and insulin signaling. Reducing ROS generation below physiological levels when the oxidative process has not yet been established may be the cause of the controversial results obtained by antioxidant therapy.