Umami-induced obesity and metabolic syndrome is mediated by nucleotide degradation and uric acid generation

Umami refers to the savoury taste that is mediated by monosodium glutamate (MSG) and enhanced by inosine monophosphate and other nucleotides. Umami foods have been suggested to increase the risk for obesity and metabolic syndrome but the mechanism is not understood. Here we show that MSG induces obesity, hypothalamic inflammation and central leptin resistance in male mice through the induction of AMP deaminase 2 and purine degradation. Mice lacking AMP deaminase 2 in both hepatocytes and neurons are protected from MSG-induced metabolic syndrome. This protection can be overcome by supplementation with inosine monophosphate, most probably owing to its degradation to uric acid as the effect can be blocked with allopurinol. Thus, umami foods induce obesity and metabolic syndrome by engaging the same purine nucleotide degradation pathway that is also activated by fructose and salt consumption. We suggest that the three tastes-sweet, salt and umami-developed to encourage food intake to facilitate energy storage and survival but drive obesity and diabetes in the setting of excess intake through similar mechanisms. Found in umami foods and known for their savoury taste, monosodium glutamate and inosine monophosphate are shown to induce metabolic syndrome in mice through induction of purine degradation in the liver and brain and through the formation of uric acid.