title: Folate deficiency is associated with oxidative stress, increased blood pressure, and insulin resistance in spontaneously hypertensive rats.
abstract: BACKGROUND
  The role of folate deficiency and associated hyperhomocysteinemia in the pathogenesis of metabolic syndrome is not fully established. In the current study, we analyzed the role of folate deficiency in pathogenesis of the metabolic syndrome in the spontaneously hypertensive rat (SHR).
  
  
  METHODS
  Metabolic and hemodynamic traits were assessed in SHR/Ola rats fed either folate-deficient or control diet for 4 weeks starting at the age of 3 months.
  
  
  RESULTS
  Compared to SHRs fed a folate-replete diet, SHRs fed a folate-deficient diet showed significantly reduced serum folate (104 ± 5 vs. 11 ± 1 nmol/L, P < 0.0005) and urinary folate excretion (4.3 ± 0.6 vs. 1.2 ± 0.1 nmol/16 h, P < 0.0005) together with a near 3-fold increase in plasma total homocysteine concentration (4.5 ± 0.1 vs 13.1 ± 0.7 μmol/L, P < 0.0005), ectopic fat accumulation in liver, and impaired glucose tolerance. Folate deficiency also increased systolic blood pressure by approximately 15 mm Hg (P < 0.01). In addition, the low-folate diet was accompanied by significantly reduced activity of antioxidant enzymes and increased concentrations of lipoperoxidation products in liver, renal cortex, and heart.
  
  
  CONCLUSIONS
  These findings demonstrate that the SHR model is susceptible to the adverse metabolic and hemodynamic effects of low dietary intake of folate. The results are consistent with the hypothesis that folate deficiency can promote oxidative stress and multiple features of the metabolic syndrome that are associated with increased risk for diabetes and cardiovascular disease.
authors: Institute of Physiology, Academy of Sciences of the Czech Republic, Prague, Czech Republic. pravenec@biomed.cas.cz
authors: Michal
authors: M
authors: Pravenec
authors: Viktor
authors: V
authors: Kozich
authors: Jakub
authors: J
authors: Krijt
authors: Jitka
authors: J
authors: Sokolová
authors: Václav
authors: V
authors: Zídek
authors: Vladimír
authors: V
authors: Landa
authors: Miroslava
authors: M
authors: Simáková
authors: Petr
authors: P
authors: Mlejnek
authors: Jan
authors: J
authors: Silhavy
authors: Olena
authors: O
authors: Oliyarnyk
authors: Ludmila
authors: L
authors: Kazdová
authors: Theodore W
authors: TW
authors: Kurtz
mesh_terms: D000818:Animals; D001794:Blood Pressure; D005492:Folic Acid / Q000378:metabolism; D005494:Folic Acid Deficiency / Q000150:complications*; D018149:Glucose Intolerance / Q000209:etiology; D020138:Hyperhomocysteinemia / Q000209:etiology; D006973:Hypertension / Q000209:etiology*; D007333:Insulin Resistance / Q000502:physiology*; D008297:Male; D024821:Metabolic Syndrome / Q000209:etiology*; D018384:Oxidative Stress; D051381:Rats; D011918:Rats, Inbred SHR
chemical_list: D005492:Folic Acid
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