Recently, scientists in Germany and the United Kingdom have collaborated to find that the deletion or mutation of the genes RNF43 and ZNRF3 triggers a regulatory signal of lipid metabolism, which in turn leads to the accumulation and inflammation of lipids in the liver. The results of this study can explain why some people are very thin, but they still have fatty liver disease. The results were published in the journal Nature Communications.
Previous cancer genomic studies have identified RNF43 and ZNRF3 as genes that mutate in colon and liver cancer patients. The research team led by Dr. Merritt Schöhl Hoch at the Max Planck Institute for Molecular Cell Biology and Genetics in Germany, together with scientists at the Gerdon Institute at the University of Cambridge in the United Kingdom, studied the mechanism by which changes in these two genes affect the development of liver disease, and explained well a once confusing paradox about why fatty liver disease occurs in thin and normal weight individuals and individuals with healthy diets.
The study found that in non-obese mice fed a normal diet, deletions or mutations in the genes RNF43 and ZNRF3 led to the accumulation of lipids and inflammation in the liver. These genetic changes lead not only to an increase in fat accumulation, but also to an increase in liver cells. In humans, these changes increase the risk of diseases such as fatty liver and liver cancer, and shorten the life expectancy of patients.
Hermann Berenguer, a postdoc in The Huber's research group, first author of the paper, explains: "With the help of organoids, we were able to grow liver cells that only mutated in these genes, and we saw that the deletion of these genes triggered a regulatory signal of lipid metabolism. The result is that lipid metabolism is no longer controlled, and lipids accumulate in the liver, leading to fatty liver. In addition, the activated signal also causes the liver cells to multiply uncontrollably. Together, these two mechanisms contribute to the progression of fatty liver disease and cancer. ”
The scientists compared the results of the experiment with patient data published by the International Union for Cancer Genomes. They examined patients with liver cancer who had a chance of survival when these two genes were mutated and found that patients with mutations in these genes had fatty liver and had a worse prognosis.
(Science and Technology Daily)