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Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor delta
Wai San Cheang1; Wing Tak Wong3; Li Wang2; Chak Kwong Cheng2; Chi Wai Lau2; Ronald Chin Wan Ma4; Aimin Xu5; Nanping Wang6; Yu Huang2; Xiao Yu Tian2
2018-11-29
Source PublicationPHARMACOLOGICAL RESEARCH
ISSN1043-6618
Volume139Pages:384-394
Abstract

Sirtuin 1 (SIRT1) activation reduces oxidative stress, inhibits inflammatory responses, and retards cellular senescence in endothelial cells in mouse models of diabetes. However, whether SIRT1 also plays a protective role in vascular dysfunction of diabetic and obese mice is not fully characterized. Previous work showed that peroxisome proliferator-activated receptor δ (PPARδ)  is beneficial in diabetic vascular dysfunction. Whether PPAR delta is involved in the beneficial effect of SIRT1 on vascular endothelial function is unknown. We used mice with overexpression of endothelial cell-specific human SIRT1 (SIRT1-Tg) and dominant-negative SIRT1 (SIRT1-mut) fed with normal chow and high fat diet to show that expression of functional SIRT1 in endothelium protects against vascular dysfunction in diet-induced obese mice. Endothelial-specific overexpression of SIRT1 improved endothelium-dependent dilation in aortas treated with risk factors including high glucose, angiotensin II, and lysophosphatidylcholine. Oral treatment with resveratrol treatment improves endothelial function in high fat diet fed wild type Ppard-wt but not in PPAR delta knockout Ppard-mut mice. Experiments on isolated arteries also showed that the effect of resveratrol or SIRT1 activator CAY10602 was inhibited by PPAR delta antagonist GSK0660. Resveratrol increased PPARδ transcriptional activity in endothelial cells. Results demonstrated here indicated that PPAR delta contributes to the beneficial effect of SIRT1 to ameliorate endothelial dysfunction in diabetic and obese mice. These results help to understand SIRT1-based strategy for treating vascular and metabolic dysfunction in the context of obesity and insulin resistance.

KeywordPparδ Sirt1 Endothelial Dysfunction Diet Induced Obesity
DOI10.1016/j.phrs.2018.11.041
Indexed BySCIE
Language英語English
WOS Research AreaPharmacology & Pharmacy
WOS SubjectPharmacology & Pharmacy
WOS IDWOS:000458709000036
PublisherACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD, 24-28 OVAL RD, LONDON NW1 7DX, ENGLAND
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Cited Times [WOS]:29   [WOS Record]     [Related Records in WOS]
Document TypeJournal article
CollectionInstitute of Chinese Medical Sciences
Corresponding AuthorYu Huang; Xiao Yu Tian
Affiliation1.Institute of Chinese Medical Sciences, State Key Laboratory of Quality Research in Chinese Medicine, University of Macau, Macau
2.School of Biomedical Sciences, Institute of Vascular Medicine, Li Ka Shing Institute of Health Sciences, CUHK Shenzhen Research Institute, Chinese University of Hong Kong, Hong Kong
3.School of Life Sciences, State Key Laboratory of Agrobiotechnology, Chinese University of Hong Kong, Hong Kong
4.Department of Medicine and Therapeutics, Hong Kong Institute of Diabetes and Obesity, Chinese University of Hong Kong, Hong Kong
5.State Key Laboratory of Pharmaceutical Biotechnology, Departments of Medicine, and Pharmacology and Pharmacy, University of Hong Kong, Hong Kong
6.Advanced Institute for Medical Sciences, Dalian Medical University, Dalian, China
First Author AffilicationInstitute of Chinese Medical Sciences
Recommended Citation
GB/T 7714
Wai San Cheang,Wing Tak Wong,Li Wang,et al. Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor delta[J]. PHARMACOLOGICAL RESEARCH,2018,139:384-394.
APA Wai San Cheang,Wing Tak Wong,Li Wang,Chak Kwong Cheng,Chi Wai Lau,Ronald Chin Wan Ma,Aimin Xu,Nanping Wang,Yu Huang,&Xiao Yu Tian.(2018).Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor delta.PHARMACOLOGICAL RESEARCH,139,384-394.
MLA Wai San Cheang,et al."Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor delta".PHARMACOLOGICAL RESEARCH 139(2018):384-394.
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