Methylglyoxal causes structural and functional alterations in adipose tissue independently of obesity

Abstract

Context:Adipose tissue is one of the first organs to develop insulin resistance even with moderate BMI. However, the contribution of developing hyperglycaemia and concomitant methylglyoxal increment to tissue dysfunction during type 2 diabetes progression was not addressed before.

Methods:Young and aged Wistar and Goto-Kakizaki rats (non-obese model of type 2 diabetes) and a group of MG-treated W rats were used to investigate the chronic effects of hyperglycaemia and ageing and specifically MG-induced mechanisms.

Results:Diabetic and aged rats showed decreased adipose tissue irrigation and interstitial hypoxia. Hyperglycaemia of diabetic rats leaded to fibrosis and accumulation of PAS-positive components, exacerbated in aged animals, which also showed decreased hipoadiponectinemia, increased MCP-1 expression and macrophage infiltration to glycated fibrotic regions. MG leaded to increased free fatty acids, hipoadiponectinemia, decreased irrigation, hypoxia and macrophage recruitment for glycated fibrotic regions.

Conclusions:MG contributes to dysfunction of adipose tissue during type 2 diabetes progression.

Keywords::

• Adipose tissue
• type 2 diabetes
• hyperglycaemia
• methylglyoxal

Acknowledgements

We thank Serviço de Anatomia Patológica, Coimbra University Hospital, especially Ilda Simões for the support with histological analysis. We thank Mário Simões from our laboratory for his technical support. For funding we thank the Portuguese Foundation for Science and Technology (FCT; project PTDC/SAU-OSM/67498/2006) and Faculty of Medicine, University of Coimbra.

Declaration of interest

The authors report no declarations of interest.