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Effect of dietary methionine on plasma and liver cholesterol concentrations in rats and expression of hepatic genes involved in cholesterol metabolism

Published online by Cambridge University Press:  08 March 2007

F. Hirche ,
A. Schröder ,
B. Knoth ,
G. I. Stangl  and
K. Eder
F. Hirche
Affiliation:
Institute of Nutritional Sciences, Martin-Luther-University of Halle-Wittenberg, 06108 Halle, Germany
A. Schröder
Affiliation:
Institute of Nutritional Sciences, Martin-Luther-University of Halle-Wittenberg, 06108 Halle, Germany
B. Knoth
Affiliation:
Institute of Nutritional Sciences, Martin-Luther-University of Halle-Wittenberg, 06108 Halle, Germany
G. I. Stangl
Affiliation:
Institute of Nutritional Sciences, Martin-Luther-University of Halle-Wittenberg, 06108 Halle, Germany
K. Eder*
Affiliation:
Institute of Nutritional Sciences, Martin-Luther-University of Halle-Wittenberg, 06108 Halle, Germany
*
*Corresponding author: Dr. Klaus Eder, fax +49 345 55 27124, email [email protected]
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Abstract

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Methionine has been shown to increase plasma cholesterol in animals. In the present study, mechanisms were investigated by which methionine could alter cholesterol metabolism. In the first experiment, forty growing rats were fed four casein-based diets differing in methionine content (2·6, 3·5, 4·5 or 6·0 g/kg) for 14 d. In the second experiment, isolated rat hepatocytes were incubated in media supplemented with 50, 100 or 200 μmol/l methionine. Dietary methionine tended to increase plasma homocysteine concentrations in the rats (P=0·058). A weak positive correlation between circulating homocysteine and plasma cholesterol was observed (R2 0·27, P<0·01). Rats fed 3·5 g/kg or more of methionine had higher concentrations of cholesterol in their plasma, in lipoprotein fractions of density (ρ kg/l) 1·006 < ρ<, 1·063 and ρ>. 1·063, and in liver than rats fed 2·6 g/kg methionine. Rats fed 6 g/kg methionine had a higher hepatic expression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and cholesterol-7α-hydroxylase than rats fed less methionine. The phosphatidylcholine:phosphatidylethanolamine ratio in rat liver increased with rising dietary methionine concentration; the relative mRNA concentrations of phosphatidylethanolamine N-methyltransferase and cystathionine β-synthase remained unaffected. Hepatocytes incubated in media supplemented with 100 or 200 μmol/l methionine had a higher cholesterol synthesis than hepatocytes incubated in a medium supplemented with 50μmol/l methionine; the LDL uptake in hepatocytes was independent of the methionine concentration of the medium. In conclusion, the present study suggests that dietary methionine induces hypercholesterolaemia at least in part via an enhanced hepatic cholesterol synthesis.

Keywords

MethionineHomocysteineCholesterol metabolismLiverRat
Type
Research Article
Information
British Journal of Nutrition , Volume 95 , Issue 5 , May 2006 , pp. 879 - 888
Copyright
Copyright © The Nutrition Society 2006

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