TEMPOL increases NAD+ and improves redox imbalance in obese mice

• Main Authors: Mayumi Yamato, Kimika Kawano, Yuki Yamanaka, Misako Saiga, Ken-ichi Yamada
• Format: Article
• Language: English
• Published: Elsevier 2016-08-01
• Series: Redox Biology
• Subjects: Obesity; Oxidative stress; Redox status; NAD+; Nitroxide
• Online Access: http://www.sciencedirect.com/science/article/pii/S2213231716300180

Continuous energy conversion is controlled by reduction–oxidation (redox) processes. NAD+ and NADH represent an important redox couple in energy metabolism. 4-Hydroxy-2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPOL) is a redox-cycling nitroxide that promotes the scavenging of several reactive oxygen species (ROS) and is reduced to hydroxylamine by NADH. TEMPOL is also involved in NAD+ production in the ascorbic acid–glutathione redox cycle. We utilized the chemical properties of TEMPOL to investigate the effects of antioxidants and NAD+/NADH modulators on the metabolic imbalance in obese mice. Increases in the NAD+/NADH ratio by TEMPOL ameliorated the metabolic imbalance when combined with a dietary intervention, changing from a high-fat diet to a normal diet. Plasma levels of the superoxide marker dihydroethidium were higher in mice receiving the dietary intervention compared with a control diet, but were normalized with TEMPOL consumption. These findings provide novel insights into redox regulation in obesity.