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

• Published in: Molecular nutrition & food research Vol. 58; no. 7; pp. 1502 - 1512
• Main Authors: Aissa, Alexandre Ferro, Tryndyak, Volodymyr, de Conti, Aline, Melnyk, Stepan, Gomes, Tarsila Daysy Ursula Hermogenes, Bianchi, Maria Lourdes Pires, James, S. Jill, Beland, Frederick A, Antunes, Lusania Maria Greggi, Pogribny, Igor P
• Format: Journal Article
• Language: English
• Published: Weinheim Wiley-VCH Verlag GmbH & Co. KGaA 01.07.2014; Blackwell Publishing Ltd; Wiley
• Subjects: albino; Animals; biochemical pathways; Biological and medical sciences; Dietary Supplements; experimental diets; Fatty liver; Feeding. Feeding behavior; Female; Fundamental and applied biological sciences. Psychology; genes; Glutathione - blood; Homocysteine; Homocysteine - blood; humans; laboratory animals; lipid metabolism; Lipid Metabolism - drug effects; liver; Liver - drug effects; Liver - metabolism; metabolites; methionine; Methionine - administration & dosage; Methionine - deficiency; Methionine-supplementation; Mice; Non-alcoholic Fatty Liver Disease - drug therapy; nutritional status; Oxidative stress; pathogenesis; stress response; Triglycerides - blood; Vertebrates: anatomy and physiology, studies on body, several organs or systems; Oxidative stress; Liver; Lipids; Supplemented diet; Fatty liver; Homocystein; Supplementation; Methionine-supplementation; Thiol; Methionine-deficiency; Nutrition; Deficiency; Rodentia; Methionine; Metabolism; Carbon; Feeding; Steatosis; Sulfur containing aminoacid; Vertebrata; Mammalia; Mouse; Animal; Mice; Homocysteine
• ISSN: 1613-4125; 1613-4133
• DOI: 10.1002/mnfr.201300726

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.