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September 1, 2022Signal Transduction and Targeted Therapy1,416 citationsOpen Access

Lactate metabolism in human health and disease

XLXiaolu LiYYYanyan YangBZBei Zhang

Key Points

  • To provide a comprehensive overview of lactate homeostasis, its signaling functions, and the physiological and pathological impacts of protein lactylation.
  • Synthesized findings from molecular, metabolic, and clinical literature regarding lactate's transition from a metabolic byproduct to a regulatory molecule.
  • Evaluated mechanistic models including the Warburg effect, the lactate shuttle hypothesis, and lactylation in cellular pathways.
  • Lactate serves as an indispensable fuel source and signaling molecule coordinating energy metabolism and communication across diverse cells and tissues.
  • Lactylation functions as a critical posttranslational modification regulating gene expression, tumor proliferation, neural excitation, and inflammatory processes.

Abstract

The current understanding of lactate extends from its origins as a byproduct of glycolysis to its role in tumor metabolism, as identified by studies on the Warburg effect. The lactate shuttle hypothesis suggests that lactate plays an important role as a bridging signaling molecule that coordinates signaling among different cells, organs and tissues. Lactylation is a posttranslational modification initially reported by Professor Yingming Zhao's research group in 2019. Subsequent studies confirmed that lactylation is a vital component of lactate function and is involved in tumor proliferation, neural excitation, inflammation and other biological processes. An indispensable substance for various physiological cellular functions, lactate plays a regulatory role in different aspects of energy metabolism and signal transduction. Therefore, a comprehensive review and summary of lactate is presented to clarify the role of lactate in disease and to provide a reference and direction for future research. This review offers a systematic overview of lactate homeostasis and its roles in physiological and pathological processes, as well as a comprehensive overview of the effects of lactylation in various diseases, particularly inflammation and cancer.

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Cite This Study

Li et al. (2022) studied this question.

synapsesocial.com/papers/69d7698cef4aa71f97f31288https://doi.org/10.1038/s41392-022-01151-3
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