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Conference Paper: Toll-like receptor 4 deficiency attenuates insulin resistance and endothelial dysfunction associated with obesity and diabetes in mice

TitleToll-like receptor 4 deficiency attenuates insulin resistance and endothelial dysfunction associated with obesity and diabetes in mice
Authors
KeywordsCardiovascular disease
Issue Date2009
PublisherHong Kong College of Cardiology. The Journal's web site is located at http://www.hkcchk.com/journals.php#3
Citation
The 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Hong Kong, 12 December 2009. In Journal of the Hong Kong College of Cardiology, 2009, v. 17 n. 2, p. 51, abstract no. OC3 How to Cite?
AbstractBACKGROUND: Aging and obesity are major risk factors for endothelial dysfunction and metabolic syndrome. Endothelial dysfunction is characterized by an impaired release of endothelium-derived relaxing (EDRF) and hyperpolarizing (EDHF) factors and enhanced production of contracting factors (EDCF). The Toll-like receptor 4 (TLR4) is a major target for lipopolysaccharide and saturated fatty acids, both of which are potent inducers of inflammation and insulin resistance. The present study was designed to evaluate the role of TLR4 in modulating metabolism and endothelial function in mice with loss-of-function mutation of TLR4. METHODS: TLR4(-/-) (C3H/HeJ) and wild type (C3H/HeOuJ) mice were subjected to standard or high fat diet. A type-2 diabetes animal model, double knockout in leptin receptor (Lepr) and TLR4 (DKO), was obtained by crossing Lepr(db/+) and TLR4(-/-) mice. Glucose and insulin tolerance tests (GTT and ITT) were carried out. Systolic blood pressure was measured by tail-cuff method. The animals were sacrificed at the age of 12 weeks. Rings of aorta, carotid artery and mesenteric artery (with or without endothelium) were suspended in a wire-myograph for measuring changes in isometric tension. Endothelial function was assessed by recording the responses to endothelium-dependent vasodilator and vasoconstrictor agonists. RESULTS: TLR4(-/-) mice under high fat diet feeding showed a better insulin sensitivity and lower blood pressure than wild type mice. DKO mice also demonstrated a significantly lower fasting blood glucose, serum cholesterol, lower blood pressure and better insulin sensitivity than Lepr(db/db) control mice. Acetylcholine-induced EDCF-mediated responses in carotid arteries were enhanced by aging, high fat diet, and genetic obesity, but were significantly attenuated by TLR4 deficiency. The contractions were inhibited by indomethacin, SC560, and S18886, but not NS398, suggesting the involvement of COX-1. Apocynin, MnTMPyP, catalase but not deferoxamine also inhibited the contractions, suggesting that reactive oxygen species may play a role. Acetylcholine-evoked hyperpolarizations were estimated in mesenteric arteries as endothelium-dependent relaxations blocked by Tram- 34 and UCL-1684. The acetylcholine-induced EDHF responses were potentiated in TLR4(-/-) mice fed with control and high fat diet. The acetylcholine and sodium nitroprusside-induced relaxations in the aorta were not different in wild type and TLR4(-/-) mice. CONCLUSION: Toll-like receptor 4 deficiency can prevent aging and obesity-induced insulin resistance and endothelial dysfunction possibly by decreasing oxidative stress.
DescriptionThis journal issue contains abstracts of the 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine
Oral Communications
Persistent Identifierhttp://hdl.handle.net/10722/106851
ISSN
2015 SCImago Journal Rankings: 0.102

 

DC FieldValueLanguage
dc.contributor.authorLiang, CFen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2010-09-25T23:33:04Z-
dc.date.available2010-09-25T23:33:04Z-
dc.date.issued2009en_HK
dc.identifier.citationThe 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Hong Kong, 12 December 2009. In Journal of the Hong Kong College of Cardiology, 2009, v. 17 n. 2, p. 51, abstract no. OC3en_HK
dc.identifier.issn1027-7811-
dc.identifier.urihttp://hdl.handle.net/10722/106851-
dc.descriptionThis journal issue contains abstracts of the 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine-
dc.descriptionOral Communications-
dc.description.abstractBACKGROUND: Aging and obesity are major risk factors for endothelial dysfunction and metabolic syndrome. Endothelial dysfunction is characterized by an impaired release of endothelium-derived relaxing (EDRF) and hyperpolarizing (EDHF) factors and enhanced production of contracting factors (EDCF). The Toll-like receptor 4 (TLR4) is a major target for lipopolysaccharide and saturated fatty acids, both of which are potent inducers of inflammation and insulin resistance. The present study was designed to evaluate the role of TLR4 in modulating metabolism and endothelial function in mice with loss-of-function mutation of TLR4. METHODS: TLR4(-/-) (C3H/HeJ) and wild type (C3H/HeOuJ) mice were subjected to standard or high fat diet. A type-2 diabetes animal model, double knockout in leptin receptor (Lepr) and TLR4 (DKO), was obtained by crossing Lepr(db/+) and TLR4(-/-) mice. Glucose and insulin tolerance tests (GTT and ITT) were carried out. Systolic blood pressure was measured by tail-cuff method. The animals were sacrificed at the age of 12 weeks. Rings of aorta, carotid artery and mesenteric artery (with or without endothelium) were suspended in a wire-myograph for measuring changes in isometric tension. Endothelial function was assessed by recording the responses to endothelium-dependent vasodilator and vasoconstrictor agonists. RESULTS: TLR4(-/-) mice under high fat diet feeding showed a better insulin sensitivity and lower blood pressure than wild type mice. DKO mice also demonstrated a significantly lower fasting blood glucose, serum cholesterol, lower blood pressure and better insulin sensitivity than Lepr(db/db) control mice. Acetylcholine-induced EDCF-mediated responses in carotid arteries were enhanced by aging, high fat diet, and genetic obesity, but were significantly attenuated by TLR4 deficiency. The contractions were inhibited by indomethacin, SC560, and S18886, but not NS398, suggesting the involvement of COX-1. Apocynin, MnTMPyP, catalase but not deferoxamine also inhibited the contractions, suggesting that reactive oxygen species may play a role. Acetylcholine-evoked hyperpolarizations were estimated in mesenteric arteries as endothelium-dependent relaxations blocked by Tram- 34 and UCL-1684. The acetylcholine-induced EDHF responses were potentiated in TLR4(-/-) mice fed with control and high fat diet. The acetylcholine and sodium nitroprusside-induced relaxations in the aorta were not different in wild type and TLR4(-/-) mice. CONCLUSION: Toll-like receptor 4 deficiency can prevent aging and obesity-induced insulin resistance and endothelial dysfunction possibly by decreasing oxidative stress.-
dc.languageengen_HK
dc.publisherHong Kong College of Cardiology. The Journal's web site is located at http://www.hkcchk.com/journals.php#3-
dc.relation.ispartofJournal of the Hong Kong College of Cardiologyen_HK
dc.subjectCardiovascular disease-
dc.titleToll-like receptor 4 deficiency attenuates insulin resistance and endothelial dysfunction associated with obesity and diabetes in miceen_HK
dc.typeConference_Paperen_HK
dc.identifier.emailLiang, CF: chaofanliang@gmail.comen_HK
dc.identifier.emailXu, A: amxu@hkucc.hku.hken_HK
dc.identifier.emailVanhoutte, PM: vanhoutt@hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros169815en_HK
dc.identifier.volume17en_HK
dc.identifier.issue2en_HK
dc.identifier.spage51en_HK
dc.identifier.epage51-
dc.publisher.placeHong Kong-
dc.description.otherThe 13th Annual Scientific Meeting of the Institute of Cardiovascular Science and Medicine, The University of Hong Kong, Hong Kong, 12 December 2009. In Journal of the Hong Kong College of Cardiology, 2009, v. 17 n. 2, p. 51, abstract no. OC3-

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