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.
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