Having shown that weight loss program can influence gene expression, science is starting to seek out out more about how this happens. According to an article recently published in Food and Chemical Toxicology, a weight loss program supplemented with or deficient in methionine, a vital amino acid abundant in eggs, meat and seafood, affects the expression of genes related to liver cell fat metabolism and genes that modify chromatin, the coiled fibers made up of DNA and proteins that form chromosomes in cells.
The study investigated how methionine influences DNA methylation, a biochemical process involving addition of a methyl radical to the DNA molecule. This is an epigenetic change, meaning an alteration within the expression profile of the genes that outline a person’s characteristics (phenotype). Epigenetic changes may be repeated in cell division and be transmitted to descendants, although they will not be similar to alterations within the DNA sequence (genotype). The links between methylation and disease are widely studied by scientists at present.
To investigate the epigenetic mechanisms involved in alterations to liver cells, the researchers fed mice a methionine-deficient or methionine-supplemented weight loss program after which extracted cells from their livers for molecular evaluation.
This study, the fourth published by the Nutrigenomics Research Group on the University of São Paulo’s Ribeirão Preto School of Pharmaceutical Sciences (FCFRP-USP) in Brazil, is predicated on data generated in the course of the PhD research of Alexandre Ferro Aissa, who was supported by FAPESP via a doctoral scholarship and a scholarship for a research internship abroad.
The study also involved collaboration with a team led by Igor Pogribny, a researcher on the National Center for Toxicological Research, a branch of the United States Food and Drug Administration (FDA). Pogribny has pioneered research on methylation and the role of methionine, specializing in hepatic steatosis (non-alcoholic fatty liver disease), currently considered an epidemic. Pogribny himself suggested Aissa investigate the motion of methionine on liver cells.
Previous studies by the FCFRP-USP group, equivalent to one reported in 2014 in Molecular Nutrition & Food Research, showed that dietary methionine deficiency and supplementation could cause molecular abnormalities related to hepatic steatosis, including altered gene expression resulting in lipid accumulation within the liver. The researchers found there that fat gathered in liver cells only when there was a deficiency of methionine, bringing a few predisposition to cirrhosis, cancer, and other diseases. “But we didn’t yet know how this happens,” Aissa told Agência FAPESP.
The findings contribute to a greater understanding of the motion of compounds present in weight loss program on gene regulation, including the impact of weight loss program on microRNAs (or miRNAs, small RNA molecules that don’t give rise to proteins but regulate the functioning of genes).
We observed that diets with inadequate levels of methionine, especially those deficient within the amino acid, could cause dysregulation of several microRNAs that play a major role in liver homeostasis.”
Lusânia Maria Greggi Antunes, corresponding creator of the article and coordinator of the Nutrigenomics Group at FCFRP-USP
“Our analyses detected 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-deficient diet having the more substantial effect,” Aissa said.
For Antunes, “The specific contribution of this study is a list of some of the biomarkers associated with a tissue alteration, such as the genes with an altered methylation pattern and the microRNAs linked to this process. All this can be used to improve diagnosis and prognosis.”
The group still has a considerable amount of data to research. The latest study, for instance, involved female mice of their reproductive period, in order that it’ll be possible to research the consequences of methionine deficiency and supplementation on their descendants. They even have data on methionine metabolism and its influence on the event of cardiac disease, including epigenetic mechanisms.
Source:
São Paulo Research Foundation (FAPESP)
Journal reference:
Aissa, A.F., et al. (2022) Epigenetic changes induced in mice liver by methionine-supplemented and methionine-deficient diets. Food and Chemical Toxicology. doi.org/10.1016/j.fct.2022.112938.