These authors contributed equally to work.
Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice
Version of Record online: 15 MAY 2014
© 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 58, Issue 7, pages 1502–1512, July 2014
How to Cite
Aissa, A. F., Tryndyak, V., de Conti, A., Melnyk, S., Gomes, T. D. U. H., Bianchi, M. L. P., James, S. J., Beland, F. A., Antunes, L. M. G. and Pogribny, I. P. (2014), Effect of methionine-deficient and methionine-supplemented diets on the hepatic one-carbon and lipid metabolism in mice. Mol. Nutr. Food Res., 58: 1502–1512. doi: 10.1002/mnfr.201300726
The views expressed in this paper do not necessarily represent those of the U.S. Food and Drug Administration.
- Issue online: 1 JUL 2014
- Version of Record online: 15 MAY 2014
- Manuscript Accepted: 24 MAR 2014
- Manuscript Revised: 19 MAR 2014
- Manuscript Received: 3 OCT 2013
- Fundação de Amparo a Pesquisa do Estado de São Paulo (FAPESP). Grant Numbers: 2010/01410-0, 2012/10872-2
- Fatty liver;
- Oxidative stress
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.
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.