Ascorbate improves metabolic abnormalities in Wrn mutant mice but not the free radical scavenger catechin.
Werner syndrome (WS) is a premature aging disorder caused by mutations in a RecQ-like DNA helicase. Mice lacking the helicase domain of the WRN homologue exhibit many phenotypic features of WS. Importantly, mutant Wrn(Deltahel/Deltahel) mice show abnormal increases in visceral fat deposition and fasting blood triglyceride levels followed by insulin resistance and high blood glucose levels. These mice also exhibit increased heart and liver tissue reactive oxygen species concomitantly with oxidative DNA damage, indicating a pro-oxidant status. We treated mice with either ascorbate or catechin hydrate for 9 months. Vitamin C supplementation reduced oxidative stress in liver and heart tissues and reversed hypertriglyceridemia, hyperglycemia, and insulin resistance and reduced fat weight in mutant Wrn(Deltahel/Deltahel) mice. Although the free scavenger catechin hydrate also reduced oxidative DNA damage in heart and liver tissues, it did not reverse any of the metabolic phenotype aspects in treated mutant mice. Finally, vitamin C and catechin hydrate did not affect the metabolic status of wild-type mice. These results indicate that vitamin C supplementation could be beneficial for WS patients.
Lebel
Michel
M
Centre de Recherche en Cancérologie de l'Université Laval, Hôpital Hôtel-Dieu de Québec, Quebec City, Canada. michel.lebel@crhdq.ulaval.ca
Massip
Laurent
L
Garand
Chantal
C
Thorin
Eric
E
D019588:Aging, Premature / Q000235:genetics; D000818:Animals; D001205:Ascorbic Acid / Q000235:genetics*; D002392:Catechin; D004249:DNA Damage; D004265:DNA Helicases / Q000235:genetics / Q000378:metabolism; D016166:Free Radical Scavengers; D006801:Humans; D006943:Hyperglycemia / Q000235:genetics*; D015228:Hypertriglyceridemia / Q000235:genetics*; D007333:Insulin Resistance / Q000235:genetics*; D051379:Mice; D009154:Mutation; D018384:Oxidative Stress / Q000235:genetics; D017382:Reactive Oxygen Species; D053484:RecQ Helicases / Q000235:genetics*; D014898:Werner Syndrome / Q000235:genetics / Q000378:metabolism; D000071657:Werner Syndrome Helicase
D016166:Free Radical Scavengers; D017382:Reactive Oxygen Species; D002392:Catechin; D004265:DNA Helicases; D053484:RecQ Helicases; D000071657:Werner Syndrome Helicase; C499253:Wrn protein, mouse; D001205:Ascorbic Acid