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Mol Nutr Food Res. 2014 Jul;58(7):1502-12. doi: 10.1002/mnfr.201300726. Epub 2014 May 15.

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

Author information

1
Department of Genetic, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Ribeirão Preto, São Paulo, Brazil.

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.

KEYWORDS:

Fatty liver; Homocysteine; Methionine-deficiency; Methionine-supplementation; Mice; Oxidative stress

PMID:
24827819
DOI:
10.1002/mnfr.201300726
[Indexed for MEDLINE]

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