Lactate, perhaps the best-known metabolic waste product, was first isolated from sour milk, in which it is produced by lactobacilli. Whereas microbes also generate other fermentation products, such as ethanol or acetone, lactate dominates in mammals. Lactate production increases when the demand for ATP and oxygen exceeds supply, as occurs during intense exercise and ischaemia. The build-up of lactate in stressed muscle and ischaemic tissues has established lactate’s reputation as a deleterious waste product. In this Perspective, we summarize emerging evidence that, in mammals, lactate also serves as a major circulating carbohydrate fuel. By providing mammalian cells with both a convenient source and sink for three-carbon compounds, circulating lactate enables the uncoupling of carbohydrate-driven mitochondrial energy generation from glycolysis. Lactate and pyruvate together serve as a circulating redox buffer that equilibrates the NADH/NAD ratio across cells and tissues. This reconceptualization of lactate as a fuel—analogous to how Hans Christian Andersen’s ugly duckling is actually a beautiful swan—has the potential to reshape the field of energy metabolism.

乳酸可能是最著名的代谢废物，最早是从酸乳中分离出来的，而乳酸是由乳酸菌产生的。微生物还产生其他发酵产物，例如乙醇或丙酮，而乳酸在哺乳动物中占主导地位。当对ATP和氧气的需求超过供应时，乳酸的产量就会增加，就像在剧烈运动和局部缺血期间那样。乳酸在压力大的肌肉和局部缺血组织中的积累已经建立了乳酸作为有害废物的声誉。在这个观点中，我们总结了新兴的证据，在哺乳动物中，乳酸盐也是主要的循环碳水化合物燃料。通过为哺乳动物细胞提供三碳化合物的便捷来源和汇聚点，循环乳酸可以使糖酵解产生的碳水化合物驱动的线粒体能量解耦。乳酸和丙酮酸一起用作循环氧化还原缓冲液，可平衡细胞和组织中NADH / NAD的比例。乳酸作为燃料的重新概念化（类似于汉斯·克里斯蒂安·安徒生的丑小鸭实际上是一只美丽的天鹅）具有重塑能量代谢领域的潜力。