Lactate: elucidating its indispensable role in human health
Shengxin Zhang, Jie Wang, Ziyu Xu, Ziyang Cheng, Bin Shao, Jiayun Yu
Abstract
Lactate, traditionally considered just a byproduct of metabolism, is now understood to be a vital regulator in energy metabolism, immune function, and epigenetic changes. Besides serving as an alternative energy source through the "lactate shuttle," it acts as a signaling molecule influencing both normal and abnormal processes in various organs. New research has emphasized its role in lactylation of histones and non-histones, a novel post-translational modification linking metabolic activity with gene expression and immune response. Lactate contributes to immunosuppression, angiogenesis, and the spread of tumors within the tumor microenvironment. Its accumulation is also linked to cardiovascular, metabolic, and neurodegenerative conditions. This shift in metabolism underscores lactate's growing importance in both health and disease, presenting novel therapeutic opportunities, especially in the treatment of cancer and metabolic disorders. This review synthesizes emerging insights into lactate's multifaceted roles and discusses promising therapeutic strategies targeting lactate metabolism, transport, and downstream signaling pathways, with an emphasis on candidates advancing toward clinical translation.