Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice
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AbstractFolic acid supplementation provides beneficial effects on endothelial functions in patients with hyperhomocysteinemia. However, its effects on vascular functions under diabetic conditions are largely unknown Therefore, the effect(s) of folic acid (5 7 and 71 mu g/kg/day for 4 weeks) on aortic relaxation was investigated using obese/diabetic (+db/+db) mice and lean littermate (+db/+m) mice. Acetylcholine-induced relaxation in +db/+db mice was less than that observed in +db/+m mice The reduced relaxation in +db/+db mice was restored by consumption of 71 Hg/kg folic acid. Acetylcholine-induced relaxation (with and without folic acid treatment) was sensitive to N-G-nitro-L-arginine methyl ester, 2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one, geldanamycin and triciribine In addition, acetylcholine-induced relaxation was attenuated by resistin The plasma level of resistin in +db/+db mice was sevenfold higher than that measured in +db/+m mice, and the elevated plasma level of resistin in +db/+db mice was reduced by 25% after treatment with 71 mu g/kg folic acid Folic acid slightly increased the ratio of reduced glutathione to oxidized glutathione in "db/+db mice Moreover, folic acid caused a reduction in PTEN (phosphatase and tensin homolog deleted on chromosome 10) expression, an Increase in the phosphorylation of endothelial nitric oxide synthase (eNOS(ser1177)) and Akt(Ser473), and an enhanced interaction of heat shock protein 90 (HSP90) with eNOS in both strains, with greater magnitude observed in +db/+db mice In conclusion, folic acid consumption improved blunted acetylcholine-induced relaxation in +db/+db mice. The mechanism may be, at least partly, attributed to enhancement of PI3K/HSP90/eNOS/Akt cascade, reduction in plasma resistin level, down-regulation of PTEN and slight modification of oxidative state. (C) 2010 Elsevier Inc All rights reserved
All Author(s) ListSeto SW, Lam TY, Or PMY, Lee WYW, Au ALS, Poon CCW, Li RWS, Chan SW, Yeung JHK, Leung GPH, Lee SMY, Ngai SM, Kwan YW
Journal nameJournal of Nutritional Biochemistry
Detailed descriptionTo ORKTS: doi: 10.1016/j.jnutbio.2009.06.015
Year2010
Month9
Day1
Volume Number21
Issue Number9
PublisherElsevier
Pages872 - 880
ISSN0955-2863
eISSN1873-4847
LanguagesEnglish-United Kingdom
Keywords+db/ plus db mice; Acetylcholine; eNOS; Folic acid; PTEN; Relaxation
Web of Science Subject CategoriesBiochemistry & Molecular Biology; BIOCHEMISTRY & MOLECULAR BIOLOGY; Nutrition & Dietetics; NUTRITION & DIETETICS

Last updated on 2020-16-09 at 00:05