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

Abstract

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

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

“…However, MG administration increased systemic free fatty acids levels, suggesting adipose tissue dysfunction, due to a higher rate of lipolysis. These results are also in accordance with our previous observations after MG treatment during 14 weeks [1]. As demonstrated before in Zucker diabetic rats (ZDF) [13, 15], pyridoxamine effects led to lower systemic levels of free fatty acids.…”

“…The significant alterations of HDL cholesterol, free fatty acids, CEL, PAS staining, TGF- β precursor, Masson Trichrome staining, Bcl-2/Bax ratio, and partially vWF were reverted by pyridoxamine. In accordance with previous reports from our laboratory, MG administration during 8 weeks did not have significant alterations in body weight, glycemia, and HbA1c [1, 7]. Once no alterations were found in the glucose metabolism, the lesions observed after MG treatment are only due to direct MG effects.…”

“…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.…”

“…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.…”

“…Irreversible formation of advanced glycation end-products (AGE) from methylglyoxal is one of the pathways responsible for diabetes-associated complications, not only due to increased aminoacid crosslinks and protein misfolding, but also due to the RAGE activation (AGE receptor) [2, 3]. We showed that increased methylglyoxal-induced AGEs accumulation in adipose tissue of Wistar rats leads to hypoadiponectinemia, increased plasma free fatty acids, fibrosis, decreased irrigation, hypoxia, higher levels of apoptotic markers (ratio Bcl-2/Bax and caspase 3), and macrophage recruitment [1]. As well, other authors showed that MG-induced AGE accumulation leads to microvascular dysfunction in other models [5–8].…”