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Title: Methylglyoxal-induced glycation changes adipose tissue vascular architecture, flow and expansion, leading to insulin resistance
Authors: Rodrigues, Tiago 
Matafome, Paulo N. 
Sereno, José 
Almeida, José
Castelhano, João 
Gamas, Luís 
Neves, Christian 
Gonçalves, Sónia 
Carvalho, Catarina 
Arslanagic, Amina 
Wilcken, Elinor 
Fonseca, Rita 
Simões, Ilda
Conde, Silvia Vilares
Castelo-Branco, Miguel 
Seiça, Raquel 
Issue Date: 10-May-2017
Publisher: Springer Nature
Project: UID/NEU/04539/2013 
QREN- COMPETE (project DoIT – Diamarker: a consortium for the discovery of novel biomarker in diabetes), POCI-01-0145-FEDER-007440 
Faculty of Medicine, University of Coimbra 
Portuguese Society of Diabetology (Portuguese National Prize of Diabetes) 
Serial title, monograph or event: Scientific Reports
Volume: 7
Issue: 1
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.
ISSN: 2045-2322
DOI: 10.1038/s41598-017-01730-3
Rights: openAccess
Appears in Collections:I&D IBILI - Artigos em Revistas Internacionais
I&D ICNAS - Artigos em Revistas Internacionais
FMUC Medicina - Artigos em Revistas Internacionais
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