Reduction of Methylglyoxal-Induced Glycation by Pyridoxamine Improves Adipose Tissue Microvascular Lesions

Background and Aims. Adipose tissue dysfunction results from many factors, including glycation-induced microvascular damages. We tested the usefulness of inhibiting methylglyoxal-induced glycation to adipose tissue microvasculature in this work, using the antioxidant and dicarbonyl scavenger drug pyridoxamine. Methods. A group of Wistar rats was treated daily with methylglyoxal (MG, 75？mg/Kg/day, 8 weeks). Half of this group was treated with pyridoxamine in the following 4 weeks (Pyr) (100？mg/Kg/day) and the other half did not have any further treatment (MG). A group of Wistar rats without MG treatment was used as control (C). Results. MG group showed decreased HDL cholesterol and increased plasma free fatty acids levels, what was reverted by pyridoxamine. MG also caused an increase of tissue CEL levels (glycation marker), as well as increased staining of PAS and Masson Trichrome-positive components. Pyridoxamine led to CEL and TGF-β levels similar to those observed in control rats and inhibited the accumulation of PAS and Masson Trichrome-positive components. MG caused a decrease of Bcl-2/Bax ratio (marker of apoptosis) and vWF staining (microvascular marker), what was partially reverted by the treatment with pyridoxamine. Conclusions. Preventing methylglyoxal-induced accumulation of glycated and fibrotic materials using pyridoxamine improves the microvascular lesions of the adipose tissue. 1. Introduction Adipose tissue dysfunction relies on many and heterogeneous factors, including impaired secretory function, insulin resistance, and lipolysis, which are believed to be caused by the activation of inflammatory mechanisms. In turn, inflammation is activated as a consequence of excessive lipid uptake, adipocyte hypertrophy, and hypoxia. Besides the limited ability of oxygen to diffuse between hypertrophic adipocytes, hypoxia also results from microvascular dysfunction and decreased compensatory angiogenesis [1–4]. These mechanisms are thought to contribute to the development and progression of type 2 diabetes. Recently, our group demonstrated that microvascular dysfunction and concomitant hypoxia may be caused by methylglyoxal-induced glycation, what may constitute a new factor for adipose tissue dysfunction during type 2 diabetes progression [1]. Thus, new strategies improving microvascular function of adipose tissue may strongly contribute to prevent these mechanisms. Methylglyoxal (MG) is a highly reactive dicarbonyl compound, endogenously formed during lipid peroxidation and glycolysis. Irreversible formation of advanced glycation end-products (AGE)