Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California, United States.
J Appl Physiol (1985). 2023 Mar 1;134(3):529-548. doi: 10.1152/japplphysiol.00497.2022. Epub 2023 Jan 12.
No longer viewed as a metabolic waste product and cause of muscle fatigue, a contemporary view incorporates the roles of lactate in metabolism, sensing and signaling in normal as well as pathophysiological conditions. Lactate exists in millimolar concentrations in muscle, blood, and other tissues and can rise more than an order of magnitude as the result of increased production and clearance limitations. Lactate exerts its powerful driver-like influence by mass action, redox change, allosteric binding, and other mechanisms described in this article. Depending on the condition, such as during rest and exercise, following carbohydrate nutrition, injury, or pathology, lactate can serve as a myokine or exerkine with autocrine-, paracrine-, and endocrine-like functions that have important basic and translational implications. For instance, lactate signaling is: involved in reproductive biology, fueling the heart, muscle adaptation, and brain executive function, growth and development, and a treatment for inflammatory conditions. Lactate also works with many other mechanisms and factors in controlling cardiac output and pulmonary ventilation during exercise. Ironically, lactate can be disruptive of normal processes such as insulin secretion when insertion of lactate transporters into pancreatic β-cell membranes is not suppressed, and in carcinogenesis when factors that suppress carcinogenesis are inhibited, whereas factors that promote carcinogenesis are upregulated. Lactate signaling is important in areas of intermediary metabolism, redox biology, mitochondrial biogenesis, neurobiology, gut physiology, appetite regulation, nutrition, and overall health and vigor. The various roles of lactate as a myokine and exerkine are reviewed. Lactate sensing and signaling is a relatively new and rapidly changing field. As a physiological signal lactate works both independently and in concert with other signals. Lactate operates via covalent binding and canonical signaling, redox change, and lactylation of DNA. Lactate can also serve as an element of feedback loops in cardiopulmonary regulation. From conception through aging lactate is not the only a myokine or exerkine, but it certainly deserves consideration as a physiological signal.
乳酸不再被视为代谢废物和肌肉疲劳的原因，而是被认为在新陈代谢、感知和信号转导中具有重要作用，无论是在正常生理状态还是病理生理状态下都是如此。乳酸在肌肉、血液和其他组织中的浓度以毫摩尔计，当生产增加和清除受到限制时，其浓度可升高一个数量级以上。乳酸通过质量作用、氧化还原变化、变构结合和本文所述的其他机制发挥其强大的驱动作用。根据具体情况，例如在休息和运动时、碳水化合物营养后、损伤或病理状态下，乳酸可以作为一种肌肉因子或运动因子，具有自分泌、旁分泌和内分泌样功能，具有重要的基础和转化意义。例如，乳酸信号转导参与生殖生物学、为心脏、肌肉适应和大脑执行功能、生长和发育提供燃料，以及炎症性疾病的治疗。乳酸还与控制运动期间心输出量和肺通气的许多其他机制和因素协同作用。具有讽刺意味的是，当乳酸转运体插入胰腺β细胞膜时没有被抑制时，乳酸会破坏正常的胰岛素分泌过程，而当抑制抑制致癌作用的因素时，在致癌作用中，促进致癌作用的因素被上调。乳酸信号转导在中间代谢、氧化还原生物学、线粒体生物发生、神经生物学、肠道生理学、食欲调节、营养以及整体健康和活力等领域具有重要作用。作为肌肉因子和运动因子，乳酸的各种作用被进行了综述。乳酸感应和信号转导是一个相对较新且快速变化的领域。作为一种生理信号，乳酸既可以独立作用，也可以与其他信号协同作用。乳酸通过共价结合和经典信号转导、氧化还原变化以及 DNA 的乳酸化发挥作用。乳酸还可以作为心肺调节反馈回路的一个组成部分。从受孕到衰老，乳酸不仅是一种肌肉因子或运动因子，而且它作为一种生理信号确实值得考虑。
