title: TEMPOL increases NAD(+) and improves redox imbalance in obese mice.
abstract: 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.
authors.affiliation: Innovation Center for Medical Redox Navigation, Kyushu University, Fukuoka, Japan. Electronic address: yamato68@redoxnavi.med.kyushu-u.ac.jp.
authors.forename: Mayumi
authors.initials: M
authors.lastname: Yamato
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Kimika
authors.initials: K
authors.lastname: Kawano
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Yuki
authors.initials: Y
authors.lastname: Yamanaka
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan.
authors.forename: Misako
authors.initials: M
authors.lastname: Saiga
authors.affiliation: Department of Bio-functional Science, Faculty of Pharmaceutical Sciences, Kyushu University, Fukuoka, Japan; JST, PRESTO, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan. Electronic address: kenyamada@phar.kyushu-u.ac.jp.
authors.forename: Ken-Ichi
authors.initials: K
authors.lastname: Yamada
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D001205:Ascorbic Acid / Q000378:metabolism; D003497:Cyclic N-Oxides / Q000008:administration & dosage*; D059305:Diet, High-Fat; D004578:Electron Spin Resonance Spectroscopy; D004734:Energy Metabolism / Q000187:drug effects; D004996:Ethidium / Q000031:analogs & derivatives / Q000378:metabolism; D005978:Glutathione / Q000378:metabolism*; D006801:Humans; D051379:Mice; D008820:Mice, Obese; D009243:NAD / Q000096:biosynthesis; D009765:Obesity / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D010084:Oxidation-Reduction / Q000187:drug effects; D018384:Oxidative Stress / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000378:metabolism; D013113:Spin Labels
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D017382:Reactive Oxygen Species; D013113:Spin Labels; D009243:NAD; C067883:dihydroethidium; D004996:Ethidium; D005978:Glutathione; D001205:Ascorbic Acid; C001803:tempol
keywords: NAD(+); Nitroxide; Obesity; Oxidative stress; Redox status