title: Effects of vitamin E on oxidative stress and atherosclerosis in an obese hyperlipidemic mouse model.
abstract: Vitamin E is a natural antioxidant that has been used in animal and human studies to determine its potential in reducing cardiovascular risk; however, a detailed study in an established obese model of atherosclerosis has yet to be performed. In our current study, we show that obesity and hyperlipidemia cause a synergistic, age-related increase in urinary isoprostane levels in mice deficient in both leptin and low-density lipoprotein receptor (ob/ob;LDLR-/-). Based upon this observation, we hypothesized that vitamin E supplementation would induce potent antiatherogenic effects in this model. Lean and obese LDLR-/- mice were provided vitamin E (2000 IU/kg) in a Western-type high-fat diet for 12 weeks. Plasma lipid parameters, such as total cholesterol (TC), triglyceride (TG) and free fatty acid, were significantly higher in obese mice compared to lean mice at baseline (P<.001). Western-type diet (WD) feeding caused an increase in TC levels in all groups (P<.001); however, TG (P<.001) and free fatty acid (P<.01) were elevated only in lean mice following WD feeding. Vitamin E supplementation neither influenced any of these parameters nor reduced urinary isoprostanes in lean or obese mice. Vitamin E supplementation in ob/ob;LDLR-/- mice resulted in a trend toward a reduction in atherosclerotic lesion area (P=.10), although no differences in lesion area were noted in lean LDLR-/- animals. These data provide evidence that vitamin E supplementation is not sufficient to reduce extreme elevations in systemic oxidative stress due to hyperlipidemia and obesity and, thus, may not be cardioprotective in this setting.
authors.affiliation: Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, Nashville, TN 37232, USA. alyssa.hasty@vanderbilt.edu
authors.forename: Alyssa H
authors.initials: AH
authors.lastname: Hasty
authors.forename: Marnie L
authors.initials: ML
authors.lastname: Gruen
authors.forename: Erin S
authors.initials: ES
authors.lastname: Terry
authors.forename: Bonnie K
authors.initials: BK
authors.lastname: Surmi
authors.forename: Robin D
authors.initials: RD
authors.lastname: Atkinson
authors.forename: Ling
authors.initials: L
authors.lastname: Gao
authors.forename: Jason D
authors.initials: JD
authors.lastname: Morrow
mesh_terms: D000818:Animals; D050197:Atherosclerosis / Q000473:pathology / Q000517:prevention & control*; D002784:Cholesterol / Q000097:blood; D003433:Crosses, Genetic; D004032:Diet; D019587:Dietary Supplements; D004195:Disease Models, Animal; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006949:Hyperlipidemias / Q000150:complications* / Q000378:metabolism; D028421:Isoprostanes / Q000652:urine; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009765:Obesity / Q000150:complications* / Q000378:metabolism; D018384:Oxidative Stress / Q000187:drug effects*; D011973:Receptors, LDL / Q000172:deficiency; D014280:Triglycerides / Q000097:blood; D014810:Vitamin E / Q000008:administration & dosage*
chemical_list: D005230:Fatty Acids, Nonesterified; D028421:Isoprostanes; D011973:Receptors, LDL; D014280:Triglycerides; D014810:Vitamin E; D002784:Cholesterol