Epigenetic changes induced in mice liver by methionine-supplemented and methionine-deficient diets

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Aissa, Alexandre Ferro ; Tryndyak, Volodymyr P. ; de Conti, Aline ; Thomazela Machado, Ana Rita ; Tuttis, Katiuska ; Machado, Carla da Silva ; Hernandes, Livia Cristina ; da Silva Santos, Patrick Wellington ; Serpeloni, Juliana Mara ; Pogribny, Igor P. ; Greggi Antunes, Lusania Maria

• Document type: Journal article
• Source: Food and Chemical Toxicology; v. 163, p. 10-pg., 2022-05-01.

Abstract

A diet deficient in donors of methyl group, such as methionine, affects DNA methylation and hepatic lipid metabolism. Methionine also affects other epigenetic mechanisms, such as microRNAs. We investigated the effects of methionine-supplemented or methionine-deficient diets on the expression of chromatin-modifying genes, global DNA methylation, the expression and methylation of genes related to lipid metabolism, and the expression of microRNAs in mouse liver. Female Swiss albino mice were fed a control diet (0.3% methionine), a methioninesupplemented diet (2% methionine), and a methionine-deficient diet (0% methionine) for 10 weeks. The genes most affected by the methionine-supplemented diet were associated with histone and DNA methyltransferases activity, while the methionine-deficient diet mostly altered the expression of histone methyltransferases genes. Both diets altered the global DNA methylation and the expression and gene-specific methylation of the lipid metabolism gene Apoa5. Both diets altered the expression of several liver homeostasis-related microRNAs, including miR-190b-5p, miR-130b-3p, miR-376c-3p, miR-411-5p, miR-29c-3p, miR-295-3p, and miR-467d-5p, with the methionine-deficient diet causing a more substantial effect. The effects of improper amounts of methionine in the diet on liver pathologies may involve a cooperative action of chromatin-modifying genes, which results in an aberrant pattern of global and gene-specific methylation, and microRNAs responsible for liver homeostasis. (AU)

• FAPESP's process: 10/01410-0 - Gene-diet interaction in mice supplemented with methionine in the fetal and postnatal periods: studies of genomic instability, methylation and expression of genes related to cardiovascular diseases
• Grantee: Alexandre Ferro Aissa
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 13/02365-6 - Methylation profile, genomic instability and gene expression evaluations related with cardiovascular diseases in mice supplemented with methionine diet
• Grantee: Lusânia Maria Greggi Antunes
• Support Opportunities: Regular Research Grants