UM  > Institute of Chinese Medical Sciences
Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5’ adenosine monophosphate-activated protein kinase-peroxisome proliferator-act
Wai San Cheang1,2; Xiao Yu Tian1,2,4; Wing Tak Wong4; Chi Wai Lau1,2; Susanna Sau-Tuen Lee3; Zhen Yu Chen3; Xiaoqiang Yao1,2; Nanping Wang5; Yu Huang1,2
2014
Source PublicationARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY
ISSN1079-5642
Volume34Issue:4Pages:830-836
Abstract

Objective—5′ Adenosine monophosphate–activated protein kinase (AMPK) interacts with peroxisome proliferator–activated receptor δ (PPARδ) to induce gene expression synergistically, whereas the activation of AMPK inhibits endoplasmic reticulum (ER) stress. Whether the vascular benefits of antidiabetic drug metformin (AMPK activator) in diabetes mellitus and obesity is mediated by PPARδ remains unknown. We aim to investigate whether PPARδ is crucial for metformin in ameliorating ER stress and endothelial dysfunction induced by high-fat diet. Approach and Results—Acetylcholine-induced endothelium-dependent relaxation in aortae was measured on wire myograph. ER stress markers were determined by Western blotting. Superoxide production in mouse aortae and NO generation in mouse aortic endothelial cells were assessed by fluorescence imaging. Endothelium-dependent relaxation was impaired and ER stress markers and superoxide level were elevated in aortae from high-fat diet–induced obese mice compared with lean mice. These effects of high-fat diet were reversed by oral treatment with metformin in diet-induced obese PPARδ wild-type mice but not in diet-induced obese PPARδ knockout littermates. Metformin and PPARδ agonist GW1516 reversed tunicamycin (ER stress inducer)-induced ER stress, oxidative stress, and impairment of  endotheliumdependent relaxation in mouse aortae as well as NO production in mouse aortic endothelial cells. Effects of metformin were abolished by cotreatment of GSK0660 (PPARδ antagonist), whereas effects of GW1516 were unaffected by compound C (AMPK inhibitor). Conclusions—Metformin restores endothelial function through inhibiting ER stress and oxidative stress and increasing NO bioavailability on activation of AMPK/PPARδ pathway in obese diabetic mice.   (Arterioscler Thromb Vasc Biol. 2014;34:830-836.)

KeywordEndothelium Nitric Oxide Obesity Vasodilation
DOIhttps://doi.org/10.1161/ATVBAHA.113.301938
Indexed BySCIE
Language英語English
WOS Research AreaHematology ; Cardiovascular System & Cardiology
WOS SubjectHematology ; Peripheral Vascular Disease
WOS IDWOS:000335607500021
Fulltext Access
Citation statistics
Cited Times [WOS]:118   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorYu Huang
Affiliation1.Chinese Univ Hong Kong, Shenzhen Res Inst, Inst Vasc Med, Hong Kong, Hong Kong, Peoples R China
2.Chinese Univ Hong Kong, Li Ka Shing Inst Hlth Sci, Hong Kong, Hong Kong, Peoples R China
3.Chinese Univ Hong Kong, Sch Life Sci, Hong Kong, Hong Kong, Peoples R China
4.Houston Methodist Res Inst, Dept Cardiovasc Sci, Houston, TX USA
5.Xi An Jiao Tong Univ, Cardiovasc Res Ctr, Xian 710049, Peoples R China
Recommended Citation
GB/T 7714
Wai San Cheang,Xiao Yu Tian,Wing Tak Wong,et al. Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5’ adenosine monophosphate-activated protein kinase-peroxisome proliferator-act[J]. ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,2014,34(4):830-836.
APA Wai San Cheang,Xiao Yu Tian,Wing Tak Wong,Chi Wai Lau,Susanna Sau-Tuen Lee,Zhen Yu Chen,Xiaoqiang Yao,Nanping Wang,&Yu Huang.(2014).Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5’ adenosine monophosphate-activated protein kinase-peroxisome proliferator-act.ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY,34(4),830-836.
MLA Wai San Cheang,et al."Metformin protects endothelial function in diet-induced obese mice by inhibition of endoplasmic reticulum stress through 5’ adenosine monophosphate-activated protein kinase-peroxisome proliferator-act".ARTERIOSCLEROSIS THROMBOSIS AND VASCULAR BIOLOGY 34.4(2014):830-836.
Files in This Item:
There are no files associated with this item.
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Wai San Cheang]'s Articles
[Xiao Yu Tian]'s Articles
[Wing Tak Wong]'s Articles
Baidu academic
Similar articles in Baidu academic
[Wai San Cheang]'s Articles
[Xiao Yu Tian]'s Articles
[Wing Tak Wong]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Wai San Cheang]'s Articles
[Xiao Yu Tian]'s Articles
[Wing Tak Wong]'s Articles
Terms of Use
No data!
Social Bookmark/Share
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.