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.

鲜味是指由味精 (MSG) 介导并由肌苷一磷酸和其他核苷酸增强的咸味。鲜味食物被认为会增加肥胖和代谢综合征的风险，但其机制尚不清楚。在这里，我们表明 MSG 通过诱导 AMP 脱氨酶 2 和嘌呤降解，在雄性小鼠中诱导肥胖、下丘脑炎症和中枢瘦素抵抗。肝细胞和神经元中均缺乏 AMP 脱氨酶 2 的小鼠免受 MSG 诱导的代谢综合征的影响。这种保护可以通过补充肌苷一磷酸来克服，这很可能是由于它降解为尿酸，因为这种作用可以被别嘌醇阻断。因此，鲜味食品通过使用相同的嘌呤核苷酸降解途径来诱发肥胖和代谢综合征，该途径也被果糖和盐的消耗激活。我们认为，甜味、盐味和鲜味这三种口味的发展是为了鼓励食物摄入，以促进能量储存和生存，但在摄入过量的情况下，通过类似的机制会导致肥胖和糖尿病。