Methylglyoxal Reshapes Hepatic and Adipose Tissue Metabolism and Increases Viability of Lymphocytes.

Background/aims: Methylglyoxal (MG) is associated with the development of metabolic disorders that modify the hepatic energetic metabolism in different ways. However, not much is known about the effects of MG on energy metabolism in healthy liver cells. Therefore, this study investigated the effects of daily MG administration to Wistar rats on hepatic and fat tissue energetic metabolism.

Methods: Rats received MG intraperitoneally at doses of 100 or 200 mg/kg for seven consecutive days in acute approach or at a dose of 25 mg/kg for one month in the chronic approach. Metabolic pathways were measured in isolated perfused livers (glycogen catabolism, gluconeogenesis and ketogenesis) as well in adipose tissue. Activities and mRNA expressions of gluconeogenic enzymes were assessed in the liver and the viability of human lymphocytes were evaluated in vitro.

Results: MG displayed systemic inflammation and the metabolic changes were similar to those of widespread catabolic diseases. MG and advanced glycation end-products stimulated lymphocyte proliferation, and MG increased the hepatic interleukin-6 expression. Rats that received MG developed insulin resistance. Gluconeogenesis was diminished and glycolysis was stimulated in livers of rats that received MG. Two factors contribute to this outcome: a deficiency in mitochondrial energy supply and a much more significant downregulation of gluconeogenic enzymes. The adipose tissue metabolism was modified in a way that the AMPK-induced lipolysis was increased in the retroperitoneal fat, but not in the mesenteric fat. Ketogenesis was increased and triglycerides content was decreased in the liver.

Conclusion: To what degree the modifications in hepatic metabolism found in MG-exposed rats can be translated to patients with a high-grade inflammation and cirrhosis is uncertain. However, it is unlikely that the strong catabolic state induced by MG would not contribute in some way to the hepatic dysfunction in advanced liver diseases.