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Article: Resveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor δ

TitleResveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor δ
Authors
KeywordsPPARδ
SIRT1
Endothelial dysfunction
Diet induced obesity
Issue Date2019
PublisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618
Citation
Pharmacological Research, 2019, v. 139, p. 384-394 How to Cite?
AbstractSirtuin 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 PPARδ 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 PPARδ knockout Ppard-mut mice. Experiments on isolated arteries also showed that the effect of resveratrol or SIRT1 activator CAY10602 was inhibited by PPARδ antagonist GSK0660. Resveratrol increased PPARδ transcriptional activity in endothelial cells. Results demonstrated here indicated that PPARδ 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.
Persistent Identifierhttp://hdl.handle.net/10722/274415
ISSN
2017 Impact Factor: 4.897
2015 SCImago Journal Rankings: 2.108

 

DC FieldValueLanguage
dc.contributor.authorCheang, WS-
dc.contributor.authorWong, W-
dc.contributor.authorWang, L-
dc.contributor.authorCheng, CK-
dc.contributor.authorLau, CW-
dc.contributor.authorMa, RCW-
dc.contributor.authorXu, A-
dc.contributor.authorWang, N-
dc.contributor.authorHuang, Y-
dc.contributor.authorTian, XY-
dc.date.accessioned2019-08-18T15:01:16Z-
dc.date.available2019-08-18T15:01:16Z-
dc.date.issued2019-
dc.identifier.citationPharmacological Research, 2019, v. 139, p. 384-394-
dc.identifier.issn1043-6618-
dc.identifier.urihttp://hdl.handle.net/10722/274415-
dc.description.abstractSirtuin 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 PPARδ 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 PPARδ knockout Ppard-mut mice. Experiments on isolated arteries also showed that the effect of resveratrol or SIRT1 activator CAY10602 was inhibited by PPARδ antagonist GSK0660. Resveratrol increased PPARδ transcriptional activity in endothelial cells. Results demonstrated here indicated that PPARδ 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.-
dc.languageeng-
dc.publisherAcademic Press. The Journal's web site is located at http://www.elsevier.com/locate/issn/10436618-
dc.relation.ispartofPharmacological Research-
dc.subjectPPARδ-
dc.subjectSIRT1-
dc.subjectEndothelial dysfunction-
dc.subjectDiet induced obesity-
dc.titleResveratrol ameliorates endothelial dysfunction in diabetic and obese mice through sirtuin 1 and peroxisome proliferator-activated receptor δ-
dc.typeArticle-
dc.identifier.emailXu, A: amxu@hkucc.hku.hk-
dc.identifier.authorityXu, A=rp00485-
dc.description.naturelink_to_subscribed_fulltext-
dc.identifier.doi10.1016/j.phrs.2018.11.041-
dc.identifier.pmid30503839-
dc.identifier.scopuseid_2-s2.0-85057796449-
dc.identifier.hkuros301606-
dc.identifier.volume139-
dc.identifier.spage384-
dc.identifier.epage394-
dc.publisher.placeUnited Kingdom-

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