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

• Main Author: Rodrigues, Tiago
• Publication Date: 2017
• Other Authors: 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
• Format: Article
• Language: eng
• Source: Repositórios Científicos de Acesso Aberto de Portugal (RCAAP)
• Download full: https://hdl.handle.net/10316/108381; https://doi.org/10.1038/s41598-017-01730-3
• topic: Adipose Tissue; Animals; Diet, High-Fat; Fasting; Fibrosis; Glycated Hemoglobin; Glycoconjugates; Glycosylation; Hypoxia; Insulin; Male; Muscle, Skeletal; Neovascularization, Physiologic; Obesity; Organ Size; Pyruvaldehyde; Rats, Wistar; Regional Blood Flow; Signal Transduction; Triglycerides; Insulin Resistance

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.