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

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


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Dietary Supplements*
  • Female
  • Glutathione / blood
  • Homocysteine / blood
  • Lipid Metabolism / drug effects*
  • Liver / drug effects*
  • Liver / metabolism
  • Methionine / administration & dosage*
  • Methionine / deficiency*
  • Mice
  • Non-alcoholic Fatty Liver Disease / drug therapy
  • Triglycerides / blood


  • Triglycerides
  • Homocysteine
  • Methionine
  • Glutathione