Metabolic Dysfunction-Associated Steatotic Liver Disease: Mechanisms Leading to Its Development with a Focus on Methylglyoxal and Counterbalancing Treatment Strategies—A Comprehensive Review

Metabolic dysfunction-associated steatotic liver disease (MASLD) is a multifactorial disorder characterized by an excessive lipids accumulation in the liver which dysregulates this organ’s function. The key contributor to MASLD development seems to be insulin resistance (IR) which affects many organs (including adipose tissue, skeletal muscles and the liver), whereas the molecular background is associated with oxidative, nitrosative and carbonyl stress. Among molecules responsible for carbonyl stress effects, methylglyoxal (MGO) seems to play the major pathological function. MGO—a by-product of glycolysis, fructolysis and lipolysis (from glycerol and fatty acids-derived ketone bodies)—is implicated in hyperglycemia, hyperlipidemia, obesity, type 2 diabetes, hypertension and cardiovascular diseases. Its causative effect in the stimulation of prooxidative and proinflammatory pathways has been well documented. Since metabolic dysregulation leading to these pathologies underlies also MASLD, the role of MGO in MASLD is addressed in this review. Potential MGO participation in the mechanism of MASLD development is discussed in regard to its role in different signaling routes leading to pathological events accelerating the disorder. Moreover, treatment strategies including approved and potential therapies in MASLD are overviewed and discussed. Among them, medications aimed at attenuating MGO-induced pathological processes are addressed.