title: Oxidative damage associated with obesity is prevented by overexpression of CuZn- or Mn-superoxide dismutase.
abstract: The development of insulin resistance is the primary step in the etiology of type 2 diabetes mellitus. There are several risk factors associated with insulin resistance, yet the basic biological mechanisms that promote its development are still unclear. There is growing literature that suggests mitochondrial dysfunction and/or oxidative stress play prominent roles in defects in glucose metabolism. Here, we tested whether increased expression of CuZn-superoxide dismutase (Sod1) or Mn-superoxide dismutase (Sod2) prevented obesity-induced changes in oxidative stress and metabolism. Both Sod1 and Sod2 overexpressing mice were protected from high fat diet-induced glucose intolerance. Lipid oxidation (F2-isoprostanes) was significantly increased in muscle and adipose with high fat feeding. Mice with increased expression of either Sod1 or Sod2 showed a significant reduction in this oxidative damage. Surprisingly, mitochondria from the muscle of high fat diet-fed mice showed no significant alteration in function. Together, our data suggest that targeting reduced oxidative damage in general may be a more applicable therapeutic target to prevent insulin resistance than is improving mitochondrial function.
authors.affiliation: The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liu
authors.affiliation: The Sam and Ann Barshop Institute for Longevity and Aging Studies, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.
authors.forename: Wenbo
authors.initials: W
authors.lastname: Qi
authors.affiliation: The Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, 78229.|Department of Cellular & Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.|Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.
authors.forename: Arlan
authors.initials: A
authors.lastname: Richardson
authors.affiliation: The Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, 78229.|Department of Cellular & Structural Biology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.|Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.
authors.forename: Holly
authors.initials: H
authors.lastname: Van Remmen
authors.affiliation: The Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, 78229.|Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.|Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Ikeno
authors.affiliation: The Geriatric Research Education and Clinical Center, South Texas Veterans Health Care System, San Antonio, Texas, 78229.|Department of Pathology, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.|Department of Molecular Medicine, The University of Texas Health Science Center at San Antonio, San Antonio, Texas, 78229.
authors.forename: Adam B
authors.initials: AB
authors.lastname: Salmon
mesh_terms: D000818:Animals; D004041:Dietary Fats / Q000009:adverse effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D008928:Mitochondria / Q000378:metabolism*; D009765:Obesity / Q000201:enzymology* / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects*; D017382:Reactive Oxygen Species / Q000378:metabolism*; D013482:Superoxide Dismutase / Q000235:genetics / Q000378:metabolism*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D004041:Dietary Fats; D017382:Reactive Oxygen Species; D013482:Superoxide Dismutase
keywords: Diabetes; F(2)-isoprostane; Mitochondria; Oxidative stress