Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance

Abstract Microvascular dysfunction has been suggested to trigger adipose tissue dysfunction in obesity. This study investigates the hypothesis that glycation impairs microvascular architecture and expandability with an impact on insulin signalling. Animal models supplemented with methylglyoxal (MG),...

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Autores principales:	Tiago Rodrigues, Paulo Matafome, José Sereno, José Almeida, João Castelhano, Luís Gamas, Christian Neves, Sónia Gonçalves, Catarina Carvalho, Amina Arslanagic, Elinor Wilcken, Rita Fonseca, Ilda Simões, Silvia Vilares Conde, Miguel Castelo-Branco, Raquel Seiça
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/effcd88d66a84a7babf0d9edf75eb38e
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spelling	oai:doaj.org-article:effcd88d66a84a7babf0d9edf75eb38e2021-12-02T15:05:26ZMethylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance10.1038/s41598-017-01730-32045-2322https://doaj.org/article/effcd88d66a84a7babf0d9edf75eb38e2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01730-3https://doaj.org/toc/2045-2322Abstract Microvascular dysfunction has been suggested to trigger adipose tissue dysfunction in obesity. This study investigates the hypothesis that glycation impairs microvascular architecture and expandability with an impact on insulin signalling. Animal models supplemented with methylglyoxal (MG), maintained with a high-fat diet (HFD) or both (HFDMG) were studied for periepididymal adipose (pEAT) tissue hypoxia and local and systemic insulin resistance. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantify blood flow in vivo, showing MG-induced reduction of pEAT blood flow. Increased adipocyte size and leptin secretion were observed only in rats feeding the high-fat diet, without the development of hypoxia. In turn, hypoxia was only observed when MG was combined (HFDMG group), being associated with impaired activation of the insulin receptor (Tyr1163), glucose intolerance and systemic and muscle insulin resistance. Accordingly, the adipose tissue angiogenic assay has shown decreased capillarization after dose-dependent MG exposure and glyoxalase-1 inhibition. Thus, glycation impairs adipose tissue capillarization and blood flow, hampering its expandability during a high-fat diet challenge and leading to hypoxia and insulin resistance. Such events have systemic repercussions in glucose metabolism and may lead to the onset of unhealthy obesity and progression to type 2 diabetes.Tiago RodriguesPaulo MatafomeJosé SerenoJosé AlmeidaJoão CastelhanoLuís GamasChristian NevesSónia GonçalvesCatarina CarvalhoAmina ArslanagicElinor WilckenRita FonsecaIlda SimõesSilvia Vilares CondeMiguel Castelo-BrancoRaquel SeiçaNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Tiago Rodrigues Paulo Matafome José Sereno José Almeida João Castelhano Luís Gamas Christian Neves Sónia Gonçalves Catarina Carvalho Amina Arslanagic Elinor Wilcken Rita Fonseca Ilda Simões Silvia Vilares Conde Miguel Castelo-Branco Raquel Seiça Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
description	Abstract Microvascular dysfunction has been suggested to trigger adipose tissue dysfunction in obesity. This study investigates the hypothesis that glycation impairs microvascular architecture and expandability with an impact on insulin signalling. Animal models supplemented with methylglyoxal (MG), maintained with a high-fat diet (HFD) or both (HFDMG) were studied for periepididymal adipose (pEAT) tissue hypoxia and local and systemic insulin resistance. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) was used to quantify blood flow in vivo, showing MG-induced reduction of pEAT blood flow. Increased adipocyte size and leptin secretion were observed only in rats feeding the high-fat diet, without the development of hypoxia. In turn, hypoxia was only observed when MG was combined (HFDMG group), being associated with impaired activation of the insulin receptor (Tyr1163), glucose intolerance and systemic and muscle insulin resistance. Accordingly, the adipose tissue angiogenic assay has shown decreased capillarization after dose-dependent MG exposure and glyoxalase-1 inhibition. Thus, glycation impairs adipose tissue capillarization and blood flow, hampering its expandability during a high-fat diet challenge and leading to hypoxia and insulin resistance. Such events have systemic repercussions in glucose metabolism and may lead to the onset of unhealthy obesity and progression to type 2 diabetes.
format	article
author	Tiago Rodrigues Paulo Matafome José Sereno José Almeida João Castelhano Luís Gamas Christian Neves Sónia Gonçalves Catarina Carvalho Amina Arslanagic Elinor Wilcken Rita Fonseca Ilda Simões Silvia Vilares Conde Miguel Castelo-Branco Raquel Seiça
author_facet	Tiago Rodrigues Paulo Matafome José Sereno José Almeida João Castelhano Luís Gamas Christian Neves Sónia Gonçalves Catarina Carvalho Amina Arslanagic Elinor Wilcken Rita Fonseca Ilda Simões Silvia Vilares Conde Miguel Castelo-Branco Raquel Seiça
author_sort	Tiago Rodrigues
title	Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
title_short	Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
title_full	Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
title_fullStr	Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
title_full_unstemmed	Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
title_sort	methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/effcd88d66a84a7babf0d9edf75eb38e
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Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance

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