Metformin is a first-line medication for type 2 diabetes mellitus (T2DM) that acts to reduce blood levels of glucose, food intake and body weight. The mechanisms behind the therapeutic effects of metformin are not completely understood and various modes of action have been proposed. Now, two independent studies published simultaneously in Nature Metabolism point towards a role for an appetite-suppressing metabolite, N-lactoyl-phenylalanine (Lac-Phe).

“We used liquid chromatography-mass spectrometry to measure Lac-Phe levels from cells, mice, and two different human cohorts,” says Xiao. Metformin treatment increased Lac-Phe levels in vitro, in mice and in humans. Further studies in primary mouse macrophages, Caco-2 cells (a human gut epithelial cell line) and BV-2 cells (a mouse microglial cell line) demonstrated that metformin was acting to inhibit complex I and drive Lac-Phe biosynthesis.

二甲双胍是治疗 2 型糖尿病 (T2DM) 的一线药物，可降低血糖水平、食物摄入量和体重。二甲双胍治疗作用背后的机制尚不完全清楚，并且已经提出了多种作用模式。现在， 《自然代谢》上同时发表的两项独立研究指出了抑制食欲的代谢物N-乳酰基苯丙氨酸 (Lac-Phe) 的作用。

“我们使用液相色谱-质谱法来测量细胞、小鼠和两个不同人类群体的 Lac-Phe 水平，”Xiao 说。二甲双胍治疗可增加体外、小鼠和人类体内的 Lac-Phe 水平。对原代小鼠巨噬细胞、Caco-2 细胞（一种人肠道上皮细胞系）和 BV-2 细胞（一种小鼠​​小胶质细胞系）的进一步研究表明，二甲双胍可抑制复合物 I 并驱动 Lac-Phe 生物合成。