Role of lactate and lactate metabolism in liver diseases (Review)

Int J Mol Med. 2024 Jul;54(1):59. doi: 10.3892/ijmm.2024.5383. Epub 2024 May 24.

Abstract

Lactate is a byproduct of glycolysis, and before the Warburg effect was revealed (in which glucose can be fermented in the presence of oxygen to produce lactate) it was considered a metabolic waste product. At present, lactate is not only recognized as a metabolic substrate that provides energy, but also as a signaling molecule that regulates cellular functions under pathophysiological conditions. Lactylation, a post‑translational modification, is involved in the development of various diseases, including inflammation and tumors. Liver disease is a major health challenge worldwide. In normal liver, there is a net lactate uptake caused by gluconeogenesis, exhibiting a higher net lactate clearance rate compared with any other organ. Therefore, abnormalities of lactate and lactate metabolism lead to the development of liver disease, and lactate and lactate metabolism‑related genes can be used for predicting the prognosis of liver disease. Targeting lactate production, regulating lactate transport and modulating lactylation may be potential treatment approaches for liver disease. However, currently there is not a systematic review that summarizes the role of lactate and lactate metabolism in liver diseases. In the present review, the role of lactate and lactate metabolism in liver diseases including liver fibrosis, non‑alcoholic fatty liver disease, acute liver failure and hepatocellular carcinoma was summarized with the aim to provide insights for future research.

Keywords: acute liver failure; hepatocellular carcinoma; lactate; lactate metabolism; non‑alcoholic fatty liver disease.

Publication types

  • Review

MeSH terms

  • Animals
  • Humans
  • Lactic Acid* / metabolism
  • Liver / metabolism
  • Liver / pathology
  • Liver Diseases* / metabolism

Substances

  • Lactic Acid

Grants and funding

The present study was supported by grants from the National Natural Science Foundation of China (grant nos. 81960507, 82073087 and 82160112), the collaborative Innovation Center of Chinese Ministry of Education (grant no. 2020-39), the Science and Technology Bureau fund of Zunyi city [grant no. ZUN SHI KE HE HZ ZI (2019)93-Hao], and the Science and Technology Plan Project of Guizhou Province [grant nos. QIAN KE HE JI cHU-ZK (2021) YI BAN451 and QIAN KE HE LH ZI (2017)7095 HAO].