A team of researchers from the National Center for Oncological Research (CNIO) has discovered an «unknown» mechanism of liver regeneration in which amino acid glutamate plays a role and is activated «only a few minutes later» than acute damage appears in the liver.
«Nutritional supplementation of glutamate can promote liver regeneration and benefit patients with severe and chronic liver damage, for example, those recovering after a hepatectomy to stimulate liver growth, or even those awaiting a transplant,» the authors of the study, published in the journal «Nature,» with the first author being CNIO researcher Maria del Del Del Ridual, stated.
The scientist has suggested that one of the objectives for future research is to «explore in more detail the possibility of using glutamate supplements in people who have undergone hepatic resection for tumor removal.»
Although the experiments were carried out in animal models, their results have been validated using bioinformatics tools through the use of human databases and hepatocytes.
The head of the growth group, nutrient factors, and cancer at the CNIO and the lead author of the study, Nabil Djouder, noted that while the liver is a regenerative organ, this function can be affected by an unhealthy diet and lifestyle, including alcohol consumption.
«Our results describe a fundamental and universal mechanism that allows the liver to regenerate after acute damage. These results can also help improve liver regenerative capacity in patients with severe liver injuries, such as cirrhosis or those who have undergone partial resection in surgery to remove a tumor,» Djouder explained.
While it was already known that liver regeneration is driven by the proliferation of liver cells, hepatocytes, a «communication» between two different organs, the liver and the bone marrow, has now been discovered, implicating the immune system through glutamate.
These hepatocytes produce glutamate and release it into the bloodstream after acute liver damage, reaching the bone marrow, activating monocytes that move towards the liver, becoming a type of immune cell known as macrophages; The presence of glutamate metabolism reprogramming in macrophages causes them to start secreting a growth factor that promotes hepatocyte proliferation, a chain of rapid events that enable liver regeneration to be triggered «in just a few minutes.»
The research also revealed that hepatocytes playing a «key role» in regeneration are those producing glutamine protein, which regulates glutamate levels; When glutamine synthesis is inhibited, more glutamate circulates, accelerating liver regeneration.
«In the future, glutamate supplementation in the diet could be recommended simply after liver removal and also to reduce liver damage caused by cirrhosis, common in patients with a poor diet or unhealthy lifestyle or other serious liver disease,» Djouder added.
The project was funded with public state funds from the Ministry of Science, Innovation, and Universities through the «Research Challenges» program and supported by the BBVA Foundation and the Spanish Association against Cancer (AECC).
