Re-Visiting Glutamate Toxicity: Implications of Monosodium Glutamate Consumption on Glutamate Metabolism and Metabolic Syndrome

Abstract

 Around a quarter of the world’s population is estimated to have metabolic syndrome (metS) which is a major risk factor for type II diabetes, cardiovascular disease and death. While the neurotoxicity of monosodium glutamate (MSG) has long been ruled out, recent trends suggest that excessive MSG intake may be associated with metS. Considering that some enzymes involved in glutamate metabolism predict early onset of metS, and that glutamate is involved in gluconeogenesis, energy production, insulin secretion and fatty acid synthesis and that it creates a perfect environment for the activation of mTOR, which subsequently leads to cell growth and autophagy inhibition, we propose that altered glutamate metabolism plays a central role in the cellular deregulation that leads to the development of metS. While recent studies have highlighted the role of aminotransferase enzymes and glutamine-recycling in metabolic syndrome, here we extend upon these concepts and provide fundamental mechanisms through which altered glutamate metabolism as a result of increased MSG consumption may play a role in the pathogenesis of metS. We propose that excessive MSG consumption leads to metS development via mechanisms involving deregulated glutamate metabolism and this is manifested through changes in glutamate metabolic enzymes and glutamate derived metabolites. Understanding whether MSG plays a role in the pathogenesis of metS is important for policy makers in food additive regulations as this may allow the prevention of debilitating diseases associated with metS. Furthermore, understanding the mechanisms involved in altered glutamate metabolism may provide important targets for diagnosing, preventing and treating metS.