After showing that diet can affect gene expression, science is beginning to find out more about how this happens. According to an article recently published in Food and chemical toxicology a diet supplemented with or deficient in methionine, an essential amino acid abundant in eggs, meat and seafood, affects the expression of genes associated with liver cell fat metabolism and genes that modify chromatin, the twisted fibers that make up DNA and proteins that form chromosomes in cells.
The study examined how methionine affects DNA methylation, a biochemical process involving the addition of a methyl radical to the DNA molecule. This is an epigenetic change, which means a change in the expression profile of the genes that define an individual’s characteristics (phenotype). Epigenetic changes can be repeated in cell division and transmitted to offspring, although they are not the same as changes in the DNA sequence (genotype). The links between methylation and disease have been extensively studied by researchers at present.
To investigate the epigenetic mechanisms involved in changes in liver cells, the researchers fed mice on a diet deficient in methionine or methionine supplementation and then removed cells from their livers for molecular analysis.
This study, the fourth published by the Nutrigenomics Research Group at the University of São Paulo’s Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP) in Brazil, is based on data generated during the PhD research by Alexandre Ferro Aissa, who was supported by FAPESP through a PhD scholarship and a scholarship for research internships abroad.
The study also involved collaboration with a team led by Igor Pogribny, a researcher at the National Center for Toxicological Research, a division of the United States Food and Drug Administration (FDA). Pogribny has been at the forefront of research into methylation and the role of methionine, focusing on hepatic steatosis (non-alcoholic fatty liver disease), which is currently considered an epidemic. Pogribny himself suggested to Aissa to study the effect of methionine on liver cells.
Previous studies conducted by the FCFRP-USP group, such as one reported in 2014 in Molecular nutrition and food research, showed that dietary methionine deficiency and dietary supplements can cause molecular abnormalities associated with hepatic steatosis, including altered gene expression leading to lipid accumulation in the liver. The researchers found that fat only accumulated in liver cells when there was a deficiency of methionine, leading to a predisposition for cirrhosis, cancer and other diseases. “But we did not yet know how this is happening,” Aissa told Agência FAPESP.
The results contribute to a better understanding of the effect of compounds present in the diet on gene regulation, including the effect of diet on microRNAs (or miRNAs, small RNA molecules that do not give rise to proteins but regulate the function of the genes).
"We observed that diets with inadequate levels of methionine, especially those that lack the amino acid, can cause dysregulation of several microRNAs that play a significant role in liver homeostasis. “
Lusânia Maria Greggi Antunes, author of the article and coordinator of the Nutrigenomics Group at FCFRP-USP
“Our analyzes identified a large number of genes that could be targeted by these microRNAs linked to liver homeostasis, including miR-190b-5p, miR-130b-3p, miR-376c-3p, miR-411-5p, miR-29c – 3p, miR-295-3p and miR-467d-5p, with methionine deficiency diet having the more significant effect, “said Aissa.
For Antunes: “The specific contribution of this study is a list of some of the biomarkers associated with a tissue change, such as the genes with an altered methylation pattern and the microRNAs associated with this process. All of this can be used for to improve diagnosis and prognosis. ”
The group still has a large amount of data to analyze. The most recent study involved, for example, female mice during their reproduction period, so that it becomes possible to analyze the effects of methionine deficiency and supplements on their offspring. They also have data on methionine metabolism and its influence on the development of heart disease, including epigenetic mechanisms.
Source:
São Paulo Research Foundation (FAPESP)
Journal reference:
Aissa, AF, et al. (2022) Epigenetic changes induced in mouse livers by methionine-supplemented and methionine-deficient diets. Food and chemical toxicology. doi.org/10.1016/j.fct.2022.112938.