This study investigated how methionine affects DNA methylation, a biochemical process that involves adding methyl radicals to DNA molecules. This is an epigenetic change, meaning a change in the gene expression profile that defines an individual's characteristic (phenotype). Epigenetic changes can be repeated during cell division and passed on to offspring, although they are not the same as changes in DNA sequence (genotype). The link between methylation and disease is currently widely studied by scientists.
To study the epigenetic mechanisms involved in liver cell alterations, the researchers fed mice a diet deficient or supplemented with methionine and then extracted cells from their livers for molecular analysis.
This study is the fourth to be published by the Nutrigenomics Research Group of the Preto School of Pharmacy (FCFRP-USP) and is based on data generated during the research of Alexandre Ferro Aissa, Ph.D., who was awarded a FAPESP PhD Fellowship and an Overseas Research Internship Fellowship support.
The study also collaborated with a team led by Igor Pogribny, a researcher at the National Center for Toxicology Research, part of the U.S. Food and Drug Administration (FDA). Pogribny pioneered the study of methylation and the role of methionine, focusing on hepatic steatosis (nonalcoholic fatty liver disease), which is now considered an epidemic. Pogribny himself suggested that Aissa study the effect of methionine on liver cells.
Previous research by the FCFRP-USP group, such as one reported in Molecular Nutrition and Food Research in 2014, showed that dietary methionine deficiency and supplementation can lead to molecular abnormalities associated with hepatic steatosis, including altered gene expression that contributes to hepatic lipid accumulation. The researchers found that only in the absence of methionine does fat accumulate in liver cells, leading to a susceptibility to cirrhosis, cancer and other diseases. "But we don't yet know how this happened," Isa told Agência FAPESP.
These findings contribute to a better understanding of the effects of compounds present in the diet on gene regulation, including the effect of diet on microRNAs (or miRNAs, small RNA molecules that do not produce proteins but regulate gene function).
Corresponding author Lusania Maria Greggi Antunes, coordinator of the FCFRP-USP Nutrigenome Group, said: "We observed that diets deficient in methionine levels, especially those deficient in the amino acid, lead to several proteins that play important roles in liver homeostasis. dysregulation of microRNAs."
"Our analysis detected a large number of genes that can be targeted by these microRNAs associated with liver homeostasis, including miR-190b-5p, miR-130b-3p, miR-376c-3p, miR-411-5p," noted Dr. , miR-29c-3p, miR-295-3p, and miR-467d-5p, while a methionine-deficient diet had a greater effect."
Antunes emphasizes: "The specific contribution of this study is to list some biomarkers associated with tissue changes, such as genes with altered methylation patterns and microRNAs associated with this process. All of these can be used to improve diagnosis and prognosis."
The organization still has a lot of data to analyze. For example, the latest study, which used female mice in their reproductive years, made it possible to analyze the effects of methionine deficiency and supplementation on their offspring. They also have data on methionine metabolism and its impact on the development of heart disease, including epigenetic mechanisms.