title: The polyphenols resveratrol and S17834 prevent the structural and functional sequelae of diet-induced metabolic heart disease in mice.
abstract: BACKGROUND
  Diet-induced obesity is associated with metabolic heart disease characterized by left ventricular hypertrophy and diastolic dysfunction. Polyphenols such as resveratrol and the synthetic flavonoid derivative S17834 exert beneficial systemic and cardiovascular effects in a variety of settings including diabetes mellitus and chronic hemodynamic overload.
  
  
  RESULTS
  We characterized the structural and functional features of a mouse model of diet-induced metabolic syndrome and used the model to test the hypothesis that the polyphenols prevent myocardial hypertrophy and diastolic dysfunction. Male C57BL/6J mice were fed a normal diet or a diet high in fat and sugar (HFHS) with or without concomitant treatment with S17834 or resveratrol for up to 8 months. HFHS diet-fed mice developed progressive left ventricular hypertrophy and diastolic dysfunction with preservation of systolic function in association with myocyte hypertrophy and interstitial fibrosis. In HFHS diet-fed mice, there was increased myocardial oxidative stress with evidence of oxidant-mediated protein modification via tyrosine nitration and 4-OH-2-nonenol adduction. HFHS diet-fed mice also exhibited increases in plasma fasting glucose, insulin, and homeostasis model assessment of insulin resistance indicative of insulin resistance. Treatment with S17834 or resveratrol prevented left ventricular hypertrophy and diastolic dysfunction. For S17834, these beneficial effects were associated with decreases in oxidant-mediated protein modifications and hyperinsulinemia and increased plasma adiponectin.
  
  
  CONCLUSIONS
  Resveratrol and S17834 administered concurrently with a HFHS diet prevent the development of left ventricular hypertrophy, interstitial fibrosis, and diastolic dysfunction. Multiple mechanisms may contribute to the beneficial effects of the polyphenols, including a reduction in myocardial oxidative stress and related protein modifications, amelioration of insulin resistance, and increased plasma adiponectin. The polyphenols resveratrol and S17834 may be of value in the prevention of diet-induced metabolic heart disease.
authors.affiliation: Cardiovascular Medicine Section, Department of Medicine, and the Myocardial and Vascular Biology Units, Boston University Medical Center, Boston, MA 02118, USA.
authors.forename: Fuzhong
authors.initials: F
authors.lastname: Qin
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Siwik
authors.forename: Ivan
authors.initials: I
authors.lastname: Luptak
authors.forename: Xiuyun
authors.initials: X
authors.lastname: Hou
authors.forename: Lei
authors.initials: L
authors.lastname: Wang
authors.forename: Akiko
authors.initials: A
authors.lastname: Higuchi
authors.forename: Robert M
authors.initials: RM
authors.lastname: Weisbrod
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Ouchi
authors.forename: Vivian H
authors.initials: VH
authors.lastname: Tu
authors.forename: Timothy D
authors.initials: TD
authors.lastname: Calamaras
authors.forename: Edward J
authors.initials: EJ
authors.lastname: Miller
authors.forename: Tony J
authors.initials: TJ
authors.lastname: Verbeuren
authors.forename: Kenneth
authors.initials: K
authors.lastname: Walsh
authors.forename: Richard A
authors.initials: RA
authors.lastname: Cohen
authors.forename: Wilson S
authors.initials: WS
authors.lastname: Colucci
mesh_terms: D052242:Adiponectin / Q000097:blood; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology / Q000627:therapeutic use*; D003971:Diastole / Q000187:drug effects*; D059305:Diet, High-Fat; D004040:Dietary Carbohydrates / Q000008:administration & dosage*; D017379:Hypertrophy, Left Ventricular / Q000517:prevention & control*; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D011499:Protein Processing, Post-Translational; D000077185:Resveratrol; D013267:Stilbenes / Q000627:therapeutic use*; D016277:Ventricular Function, Left / Q000187:drug effects
chemical_list: C438505:6,8-diallyl 5,7-dihydroxy 2-(2-allyl 3-hydroxy 4-methoxyphenyl)1-H benzo(b)pyran-4-one; D052242:Adiponectin; D000959:Antihypertensive Agents; D001578:Benzopyrans; D004040:Dietary Carbohydrates; D013267:Stilbenes; D000077185:Resveratrol