Methylglyoxal in Cardiometabolic Disorders: Routes Leading to Pathology Counterbalanced by Treatment Strategies

Abstract

Methylglyoxal (MGO) is the major compound belonging to reactive carbonyl species (RCS) responsible for the generation of advanced glycation end products (AGEs). Its upregulation, followed by deleterious effects at the cellular and systemic levels, is associated with metabolic disturbances (hyperglycemia/hyperinsulinemia/insulin resistance/hyperlipidemia/inflammatory processes/carbonyl stress/oxidative stress/hypoxia). Therefore, it is implicated in a variety of disorders, including metabolic syndrome, diabetes mellitus, and cardiovascular diseases. In this review, an interplay between pathways leading to MGO generation and scavenging is addressed in regard to this system’s impairment in pathology. The issues associated with mechanistic MGO involvement in pathological processes, as well as the discussion on its possible causative role in cardiometabolic diseases, are enclosed. Finally, the main strategies aimed at MGO and its AGEs downregulation with respect to cardiometabolic disorders treatment are addressed. Potential glycation inhibitors and MGO scavengers are discussed, as well as the mechanisms of their action.

Keywords

• methylglyoxal
• glyoxalase
• advanced glycation end products
• MG-H1
• metabolic syndrome
• insulin resistance