Lactate may play an important regulatory role in cancer, other diseases

Scientists have identified a previously unknown regulatory role for well-known byproduct of cell metabolism that could help shed light on cancer, atherosclerosis, sepsis, and a host of other diseases. 

The study focused on lactate, a chemical widely known as an energy source and a metabolic byproduct. However, its non-metabolic functions are largely unknown.

Using human and mouse cells, researchers showed that lactate may play a key regulatory role in cells by causing changes in gene expression. Specifically, they found that lactate can modify histones, which are a group of proteins found in cells that organize DNA into structural units and control which genes are expressed. In turn, those genes determine cell type and function.

The researchers demonstrated that “histone lactylation” alters these structural units to change the combination of genes expressed and functions of the macrophages, white blood cells that play an important role in infections and cancer. Findings from the study suggest that high lactate and histone lactylation levels in macrophages may contribute to the formation of tumors and their progression.  The discovery draws an exciting link between cellular metabolism and gene regulation that was previously unknown and could have promising implications for human health, the researchers said.

The study, partly funded by NHLBI, appeared in Nature.