Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice

Author(s)

Aissa, Alexandre Ferro ^[1] ; Tryndyak, Volodymyr ^[2] ; de Conti, Aline ^[2] ; Melnyk, Stepan ^[3] ; Ursula Hermogenes Gomes, Tarsila Daysy ^[4] ; Pires Bianchi, Maria Lourdes ^[4] ; James, S. Jill ^[3] ; Beland, Frederick A. ^[2] ; Greggi Antunes, Lusania Maria ^{[4, 1]} ; Pogribny, Igor P. ^[2]

Affiliation

^[1] Univ Sao Paulo, Fac Med Ribeirao Preto, Dept Genet, Sao Paulo - Brazil

^[2] US FDA, Div Biochem Toxicol, NCTR, Jefferson, AR 72079 - USA

^[3] Univ Arkansas Med Sci, Dept Pediat, Little Rock, AR 72205 - USA

^[4] Univ Sao Paulo, Fac Pharmaceut Sci Ribeirao Preto, Dept Clin Anal Toxicol & Food Sci, Sao Paulo - Brazil

• Document type: Journal article
• Source: MOLECULAR NUTRITION & FOOD RESEARCH; v. 58, n. 7, p. 1502-1512, JUL 2014.
• Web of Science Citations: 15

Abstract

Scope: A compromised nutritional status in methyl-group donors may provoke several molecular alterations triggering the development of nonalcoholic fatty liver disease (NAFLD) in humans and experimental animals. In this study, we investigated a role and the underlying molecular mechanisms of methionine metabolic pathway malfunctions in the pathogenesis of NAFLD. Methods and results: We fed female Swiss albino mice a control (methionine-adequate) diet and two experimental (methionine-deficient or methionine-supplemented) diets for 10 weeks, and the levels of one-carbon metabolites, expression of one-carbon and lipid metabolism genes in the livers were evaluated. We demonstrate that both experimental diets increased hepatic levels of S-adenosyl-L-homocysteine and homocysteine, altered expression of one-carbon and lipid metabolism genes, and caused lipid accumulation, especially in mice fed the methionine-deficient diet. Markers of oxidative and ER stress response were also elevated in the livers of mice fed either diet. Conclusion: Our findings indicate that both dietary methionine deficiency and methionine supplementation can induce molecular abnormalities in the liver associated with the development of NAFLD, including deregulation in lipid and one-carbon metabolic pathways, and induction of oxidative and ER stress. These pathophysiological events may ultimately lead to lipid accumulation in the livers, triggering the development of NAFLD. (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: 12/10872-2 - MicroRNA expression analysis in female mice treated with methionine-deficient or -supplemented diets during pregnancy
• Grantee: Alexandre Ferro Aissa
• Support Opportunities: Scholarships abroad - Research Internship - Doctorate