Article: Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice
| Title | Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Authors | Seto, SW4 Lam, TY4 Or, PMY4 Lee, WYW4 Au, ALS4 Poon, CCW4 Li, RWS1 Chan, SW3 Yeung, JHK4 Leung, GPH1 Lee, SMY2 Ngai, SM4 Kwan, YW4 | ||||||||||||
| Keywords | +db/+db mice Acetylcholine ENOS Folic acid PTEN Relaxation | ||||||||||||
| Issue Date | 2010 | ||||||||||||
| Publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio | ||||||||||||
| Citation | Journal Of Nutritional Biochemistry, 2010, v. 21 n. 9, p. 872-880 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jnutbio.2009.06.015 | ||||||||||||
| Abstract | 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 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 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 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 (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. © 2010 Elsevier Inc. | ||||||||||||
| ISSN | 0955-2863 2011 Impact Factor: 3.891 2011 SCImago Journal Rankings: 0.233 | ||||||||||||
| DOI | http://dx.doi.org/10.1016/j.jnutbio.2009.06.015 | ||||||||||||
| ISI Accession Number ID | WOS:000281710700012
Funding Information: We are grateful to the Li Ka Shing Institute of Health Sciences and the Institute of Vascular Medicine (Faculty of Medicine, The Chinese University of Hong Kong) for financial support (to Y.W. Kwan). This project was financially supported by the RGC Earmarked Grants of Hong Kong SAR, People's Republic of China (reference nos. 4107/01M and 4166/02M, project code 2140565), and Direct Grants for Research (The Chinese University of Hong Kong) (reference no. 2401149; project code.; 2041231 and 2401296). Mr. S.W. Seto, Ms. T.Y. Lam, Ms. Alice LS. Au and Mr. Wayne Y.W. Lee are recipients of postgraduate studentships from the Department of Pharmacology (The Chinese University Hong Kong). We thank Ms. Jian Hong Wu (State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University) for technical assistance in measuring cholesterol and lipoproteins levels. Provision of the Student Campus Work Scheme by the Chou's Foundation Fund and the Student Campus Work Scheme (Shaw College, The Chinese University of Hong Kong) is also. appreciated. Proofreading of the manuscript by Mr. Ho Yeung Lam is also acknowledged. | ||||||||||||
| References | References in Scopus |
| dc.contributor.author | Seto, SW | ||||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
| dc.contributor.author | Lam, TY | ||||||||||||
| dc.contributor.author | Or, PMY | ||||||||||||
| dc.contributor.author | Lee, WYW | ||||||||||||
| dc.contributor.author | Au, ALS | ||||||||||||
| dc.contributor.author | Poon, CCW | ||||||||||||
| dc.contributor.author | Li, RWS | ||||||||||||
| dc.contributor.author | Chan, SW | ||||||||||||
| dc.contributor.author | Yeung, JHK | ||||||||||||
| dc.contributor.author | Leung, GPH | ||||||||||||
| dc.contributor.author | Lee, SMY | ||||||||||||
| dc.contributor.author | Ngai, SM | ||||||||||||
| dc.contributor.author | Kwan, YW | ||||||||||||
| dc.date.accessioned | 2011-08-26T14:26:03Z | ||||||||||||
| dc.date.available | 2011-08-26T14:26:03Z | ||||||||||||
| dc.date.issued | 2010 | ||||||||||||
| dc.description.abstract | 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 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 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 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 (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. © 2010 Elsevier Inc. | ||||||||||||
| dc.description.nature | Link_to_subscribed_fulltext | ||||||||||||
| dc.identifier.citation | Journal Of Nutritional Biochemistry, 2010, v. 21 n. 9, p. 872-880 [How to Cite?] DOI: http://dx.doi.org/10.1016/j.jnutbio.2009.06.015 | ||||||||||||
| dc.identifier.citeulike | 6198270 | ||||||||||||
| dc.identifier.doi | http://dx.doi.org/10.1016/j.jnutbio.2009.06.015 | ||||||||||||
| dc.identifier.epage | 880 | ||||||||||||
| dc.identifier.hkuros | 189170 | ||||||||||||
| dc.identifier.isi | WOS:000281710700012
Funding Information: We are grateful to the Li Ka Shing Institute of Health Sciences and the Institute of Vascular Medicine (Faculty of Medicine, The Chinese University of Hong Kong) for financial support (to Y.W. Kwan). This project was financially supported by the RGC Earmarked Grants of Hong Kong SAR, People's Republic of China (reference nos. 4107/01M and 4166/02M, project code 2140565), and Direct Grants for Research (The Chinese University of Hong Kong) (reference no. 2401149; project code.; 2041231 and 2401296). Mr. S.W. Seto, Ms. T.Y. Lam, Ms. Alice LS. Au and Mr. Wayne Y.W. Lee are recipients of postgraduate studentships from the Department of Pharmacology (The Chinese University Hong Kong). We thank Ms. Jian Hong Wu (State Key Laboratory of Chinese Medicine and Molecular Pharmacology, Department of Applied Biology and Chemical Technology, The Hong Kong Polytechnic University) for technical assistance in measuring cholesterol and lipoproteins levels. Provision of the Student Campus Work Scheme by the Chou's Foundation Fund and the Student Campus Work Scheme (Shaw College, The Chinese University of Hong Kong) is also. appreciated. Proofreading of the manuscript by Mr. Ho Yeung Lam is also acknowledged. | ||||||||||||
| dc.identifier.issn | 0955-2863 2011 Impact Factor: 3.891 2011 SCImago Journal Rankings: 0.233 | ||||||||||||
| dc.identifier.issue | 9 | ||||||||||||
| dc.identifier.pmid | 19879746 | ||||||||||||
| dc.identifier.scopus | eid_2-s2.0-77955847141 | ||||||||||||
| dc.identifier.spage | 872 | ||||||||||||
| dc.identifier.uri | http://hdl.handle.net/10722/137484 | ||||||||||||
| dc.identifier.volume | 21 | ||||||||||||
| dc.language | eng | ||||||||||||
| dc.publisher | Elsevier Inc. The Journal's web site is located at http://www.elsevier.com/locate/jnutbio | ||||||||||||
| dc.publisher.place | United States | ||||||||||||
| dc.relation.ispartof | Journal of Nutritional Biochemistry | ||||||||||||
| dc.relation.references | References in Scopus | ||||||||||||
| dc.subject.mesh | Acetylcholine - pharmacology | ||||||||||||
| dc.subject.mesh | Diabetes Mellitus - metabolism | ||||||||||||
| dc.subject.mesh | Folic Acid - metabolism - pharmacology | ||||||||||||
| dc.subject.mesh | Resistin - metabolism | ||||||||||||
| dc.subject.mesh | Vasodilation - drug effects | ||||||||||||
| dc.subject | +db/+db mice | ||||||||||||
| dc.subject | Acetylcholine | ||||||||||||
| dc.subject | ENOS | ||||||||||||
| dc.subject | Folic acid | ||||||||||||
| dc.subject | PTEN | ||||||||||||
| dc.subject | Relaxation | ||||||||||||
| dc.title | Folic acid consumption reduces resistin level and restores blunted acetylcholine-induced aortic relaxation in obese/diabetic mice | ||||||||||||
| dc.type | Article |
- The University of Hong Kong
- University of Macau
- Hong Kong Polytechnic University
- Chinese University of Hong Kong