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Conference Paper: Loss-of-function in Toll-like receptor 4 (TLR4) alleviates metabolic syndrome and endothelial dysfunction in genetically obese mice

TitleLoss-of-function in Toll-like receptor 4 (TLR4) alleviates metabolic syndrome and endothelial dysfunction in genetically obese mice
Authors
KeywordsBiology
Physiology medical sciences
Issue Date2010
PublisherWiley-Blackwell Publishing Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1748-1708
Citation
The 12th Symposium on Vascular Neuroeffector Mechanisms, Odense, Denmark, 24-26 July 2010. In Acta Physiologica, 2010, v. 199 suppl. 680, p. 15 How to Cite?
AbstractThe present study analyzes, in mice with loss-of-function mutation, the role of toll like receptor-4, a target for saturated fatty acids, in modulating metabolism and endothelial function. A type-2 diabetes model with double knockout (DKO) of leptin receptors (Lepr) and TLR4, was obtained by crossing Leprdb/+ and TLR4-/- mice. Glucose and insulin tolerance tests were performed when the mice were eight weeks old. Mice were sacrificed and rings [with and without endothelium] of their aorta, carotid artery or mesenteric artery rings were studied. DKO mice exhibited a higher body weight increase, had significantly lower fasting serum levels of glucose and cholesterol and higher insulin concentration than Leprdb/db control mice. The DKO mice also showed improved glucose tolerance and insulin sensitivity. Endothelium-dependent contractions (EDC) to acetylcholine of the carotid arteries were enhanced by genetic obesity, but were attenuated in DKO mice. Contractions were inhibited by indomethacin and SC560, suggesting the involvement of COX-1. Apocynin, MnTMPyP, catalase, DETCA, but not deferoxamine and tiron inhibited EDC, suggesting a role for H2O2. Both the basal and acetylcholine-stimulated production of superoxide anions was markedly down-regulated in carotid arteries of DKO mice. The eNOS monomer to dimer ratio was higher in aortae of Leprdb/db control mice but normalized in DKO mice. In control but not in DKO mice, activation of TLR4 by lipopolysaccharide potentiated the contractions whereas inhibitors blocking TLR4 signaling [including SP600128 (JNK), PD98058 (ERK) and SB203508 (MAPK)] attenuated the contractions, defining the pathway downstream of TLR4 activation. Acetylcholine-induced, endothelium-dependent relaxations and hyperpolarizations (determined in aortae and mesenteric arteries, respectively) were blunted by genetic obesity, but not in DKO mice. Thus, TLR4 deficiency curtails metabolic syndrome and endothelial dysfunction by increasing insulin secretion and decreasing inflammation and oxidative stress.
DescriptionJournal supplement has title: Abstracts for the 12th Symposium on Vascular Neuroeffector Mechanisms
Abstract number: 09
Persistent Identifierhttp://hdl.handle.net/10722/126894
ISSN
2015 Impact Factor: 4.066
2015 SCImago Journal Rankings: 1.690

 

DC FieldValueLanguage
dc.contributor.authorLiang, CFen_HK
dc.contributor.authorXu, Aen_HK
dc.contributor.authorVanhoutte, PMen_HK
dc.date.accessioned2010-10-31T12:54:43Z-
dc.date.available2010-10-31T12:54:43Z-
dc.date.issued2010en_HK
dc.identifier.citationThe 12th Symposium on Vascular Neuroeffector Mechanisms, Odense, Denmark, 24-26 July 2010. In Acta Physiologica, 2010, v. 199 suppl. 680, p. 15en_HK
dc.identifier.issn1748-1708-
dc.identifier.urihttp://hdl.handle.net/10722/126894-
dc.descriptionJournal supplement has title: Abstracts for the 12th Symposium on Vascular Neuroeffector Mechanisms-
dc.descriptionAbstract number: 09-
dc.description.abstractThe present study analyzes, in mice with loss-of-function mutation, the role of toll like receptor-4, a target for saturated fatty acids, in modulating metabolism and endothelial function. A type-2 diabetes model with double knockout (DKO) of leptin receptors (Lepr) and TLR4, was obtained by crossing Leprdb/+ and TLR4-/- mice. Glucose and insulin tolerance tests were performed when the mice were eight weeks old. Mice were sacrificed and rings [with and without endothelium] of their aorta, carotid artery or mesenteric artery rings were studied. DKO mice exhibited a higher body weight increase, had significantly lower fasting serum levels of glucose and cholesterol and higher insulin concentration than Leprdb/db control mice. The DKO mice also showed improved glucose tolerance and insulin sensitivity. Endothelium-dependent contractions (EDC) to acetylcholine of the carotid arteries were enhanced by genetic obesity, but were attenuated in DKO mice. Contractions were inhibited by indomethacin and SC560, suggesting the involvement of COX-1. Apocynin, MnTMPyP, catalase, DETCA, but not deferoxamine and tiron inhibited EDC, suggesting a role for H2O2. Both the basal and acetylcholine-stimulated production of superoxide anions was markedly down-regulated in carotid arteries of DKO mice. The eNOS monomer to dimer ratio was higher in aortae of Leprdb/db control mice but normalized in DKO mice. In control but not in DKO mice, activation of TLR4 by lipopolysaccharide potentiated the contractions whereas inhibitors blocking TLR4 signaling [including SP600128 (JNK), PD98058 (ERK) and SB203508 (MAPK)] attenuated the contractions, defining the pathway downstream of TLR4 activation. Acetylcholine-induced, endothelium-dependent relaxations and hyperpolarizations (determined in aortae and mesenteric arteries, respectively) were blunted by genetic obesity, but not in DKO mice. Thus, TLR4 deficiency curtails metabolic syndrome and endothelial dysfunction by increasing insulin secretion and decreasing inflammation and oxidative stress.-
dc.languageengen_HK
dc.publisherWiley-Blackwell Publishing Ltd. The Journal's web site is located at http://www.wiley.com/bw/journal.asp?ref=1748-1708-
dc.relation.ispartofActa Physiologicaen_HK
dc.rightsThe definitive version is available at www3.interscience.wiley.com-
dc.subjectBiology-
dc.subjectPhysiology medical sciences-
dc.titleLoss-of-function in Toll-like receptor 4 (TLR4) alleviates metabolic syndrome and endothelial dysfunction in genetically obese 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, PMGR: vanhoutt@hku.hken_HK
dc.identifier.authorityXu, A=rp00485en_HK
dc.identifier.authorityVanhoutte, PM=rp00238en_HK
dc.description.naturelink_to_OA_fulltext-
dc.identifier.hkuros175214en_HK
dc.identifier.volume199en_HK
dc.identifier.issuesuppl. 680-
dc.identifier.spage15en_HK
dc.identifier.epage15-
dc.publisher.placeUnited Kingdom-
dc.description.otherThe 12th Symposium on Vascular Neuroeffector Mechanisms, Odense, Denmark, 24-26 July 2010. In Acta Physiologica, 2010, v. 199 suppl. 680, p. 15-

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