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Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice

Seto, Sai Wang; Lam, Tsz Yan; Or, Penelope Mei Yu; Lee, Wayne Yuk Wai; Au, Alice Lai Shan; Poon, Christina Chui Wa; Li, Rachel; Chan, S. W.; Yeung, John Hok Keung; Leung, George P. H.; Lee, Simon M.Y.; Ngai, Sai Ming; Kwan, Y. W.

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Folic 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 μg/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...[Show more]

dc.contributor.authorSeto, Sai Wang
dc.contributor.authorLam, Tsz Yan
dc.contributor.authorOr, Penelope Mei Yu
dc.contributor.authorLee, Wayne Yuk Wai
dc.contributor.authorAu, Alice Lai Shan
dc.contributor.authorPoon, Christina Chui Wa
dc.contributor.authorLi, Rachel
dc.contributor.authorChan, S. W.
dc.contributor.authorYeung, John Hok Keung
dc.contributor.authorLeung, George P. H.
dc.contributor.authorLee, Simon M.Y.
dc.contributor.authorNgai, Sai Ming
dc.contributor.authorKwan, Y. W.
dc.date.accessioned2015-12-13T22:43:55Z
dc.identifier.issn0955-2863
dc.identifier.urihttp://hdl.handle.net/1885/79421
dc.description.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 μg/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 μg/kg folic acid. Acetylcholine-induced relaxation (with and without folic acid treatment) was sensitive to NG-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 μg/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 (eNOSSer1177) and AktSer473, 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.
dc.publisherElsevier BV
dc.sourceJournal of Nutritional Biochemistry
dc.subjectKeywords: acetylcholine; endothelial nitric oxide synthase; folic acid; geldanamycin; glutathione; glutathione disulfide; heat shock protein 90; n nitro l arginine methyl ester, 2 (4 morpholinyl) 8 phenyl 1 benzopyran 4 one; phosphatidylinositol 3,4,5 trisphosphate +db/+db mice; Acetylcholine; ENOS; Folic acid; PTEN; Relaxation
dc.titleFolic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice
dc.typeJournal article
local.description.notesImported from ARIES
local.identifier.citationvolume21
dc.date.issued2010
local.identifier.absfor060199 - Biochemistry and Cell Biology not elsewhere classified
local.identifier.ariespublicationf5625xPUB7864
local.type.statusPublished Version
local.contributor.affiliationSeto, Sai Wang, The Chinese University of Hong Kong
local.contributor.affiliationLam, Tsz Yan, The Chinese University of Hong Kong
local.contributor.affiliationOr, Penelope Mei Yu, The Chinese University of Hong Kong
local.contributor.affiliationLee, Wayne Yuk Wai, The Chinese University of Hong Kong
local.contributor.affiliationAu, Alice Lai Shan, The Chinese University of Hong Kong
local.contributor.affiliationPoon, Christina Chui Wa, The Chinese University of Hong Kong
local.contributor.affiliationLi, Rachel, College of Medicine, Biology and Environment, ANU
local.contributor.affiliationChan, S. W., The Hong Kong Polytechnic University
local.contributor.affiliationYeung, John Hok Keung, The Chinese University of Hong Kong
local.contributor.affiliationLeung, George P. H., The University of Hong Kong
local.contributor.affiliationLee, Simon M.Y., The University of Macau
local.contributor.affiliationNgai, Sai Ming, The Chinese University of Hong Kong
local.contributor.affiliationKwan, Y. W., The Chinese University of Hong Kong
local.description.embargo2037-12-31
local.bibliographicCitation.issue9
local.bibliographicCitation.startpage872
local.bibliographicCitation.lastpage880
local.identifier.doi10.1016/j.jnutbio.2009.06.015
dc.date.updated2016-02-24T09:37:53Z
local.identifier.scopusID2-s2.0-77955847141
CollectionsANU Research Publications

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