UM
PPAR delta Is Required for Exercise to Attenuate Endoplasmic Reticulum Stress and Endothelial Dysfunction in Diabetic Mice
Cheang, Wai San; Wong, Wing Tak; Zhao, Lei; Xu, Jian; Wang, Li; Lau, Chi Wai; Chen, Zhen Yu; Ma, Ronald Ching Wan; Xu, Aimin; Wang, Nanping; Tian, Xiao Yu; Huang, Yu
2017-02
Source PublicationDIABETES
ISSN0012-1797
Volume66Issue:2Pages:519-528
AbstractPhysical activity has profound benefits on health, especially on cardiometabolic wellness. Experiments in rodents with trained exercise have shown that exercise improves vascular function and reduces vascular inflammation by modulating the balance between nitric oxide (NO) and oxidative stress. However, the upstream regulator of exercise induced vascular benefits is unclear. We aimed to investigate the involvement of peroxisome proliferator-activated receptor delta (PPAR delta) in exercise-induced vascular functional improvement. We show that PPAR delta is a crucial mediator for exercise to exert a beneficial effect on the vascular endothelium in diabetic mice. In db/db mice and high-fat diet-induced obese mice, 4 weeks of treadmill exercise restored endothelium-dependent vasodilation of aortas and flow-mediated vasodilation in mesenteric resistance arteries, whereas genetic ablation of Ppard abolished such improvements. Exercise induces AMPK activation and subsequent PPAR delta activation, which help to reduce endoplasmic reticulum (ER) and oxidative stress, thus increasing NO bioavailability in endothelial cells and vascular tissues. Chemical chaperones 4-phenylbutyric acid and tauroursodeoxycholic acid decrease ER stress and protect against endothelial dysfunction in diabetic mice. The results demonstrate that PPAR delta-mediated inhibition of ER stress contributes to the vascular benefits of exercise and provides potentially effective targets for treating diabetic vasculopathy.
DOI10.2337/db15-1657
URLView the original
Indexed BySCI
Language英语
WOS Research AreaEndocrinology & Metabolism
WOS SubjectEndocrinology & Metabolism
WOS IDWOS:000392691000028
PublisherAMER DIABETES ASSOC
The Source to ArticleWOS
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Cited Times [WOS]:18   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionUniversity of Macau
Recommended Citation
GB/T 7714
Cheang, Wai San,Wong, Wing Tak,Zhao, Lei,et al. PPAR delta Is Required for Exercise to Attenuate Endoplasmic Reticulum Stress and Endothelial Dysfunction in Diabetic Mice[J]. DIABETES,2017,66(2):519-528.
APA Cheang, Wai San.,Wong, Wing Tak.,Zhao, Lei.,Xu, Jian.,Wang, Li.,...&Huang, Yu.(2017).PPAR delta Is Required for Exercise to Attenuate Endoplasmic Reticulum Stress and Endothelial Dysfunction in Diabetic Mice.DIABETES,66(2),519-528.
MLA Cheang, Wai San,et al."PPAR delta Is Required for Exercise to Attenuate Endoplasmic Reticulum Stress and Endothelial Dysfunction in Diabetic Mice".DIABETES 66.2(2017):519-528.
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