British Journal of Nutrition

Full Papers

Molecular Nutrition

Study of molecular targets influencing homocysteine and cholesterol metabolism in growing rats by manipulation of dietary selenium and methionine concentrations

Nicole M. Wolfa1, Kristin Muellera1, Frank Hirchea1, Erika Mosta2, Josef Pallaufa2 and Andreas S. Muellera1 c1

a1 Institute of Agricultural and Nutritional Sciences, Preventive Nutrition Group, Martin Luther University Halle Wittenberg, Von-Danckelmann-Platz 2, D-06120 Halle/Saale, Germany

a2 Institute of Animal Nutrition and Nutritional Physiology, Interdisciplinary Research Centre, Justus Liebig University Giessen, Heinrich-Buff-Ring 26–32, D-35392 Giessen, Germany

Abstract

Inconsistent results exist from human and animal studies for Se and methionine (Met) regarding their influence on homocysteine (HCys) and cholesterol (Chol) metabolism. To elucidate these contradictions, sixty-four weanling albino rats were divided into eight groups of 8, and were fed diets containing four different Se levels (15, 50, 150 and 450 μg/kg) either in combination with the recommended Met level of 3 g/kg (C15, C50, C150 and C450) or with an increased Met concentration of 15 g/kg (M15, M50, M150 and M450) for 8 weeks. Plasma HCys was twofold higher in the Se-supplemented C groups than in group C15. Met addition also doubled plasma HCys compared with the respective C groups. In contrast, the expression of the key enzymes of glutathione biosynthesis in the liver was significantly lowered by Se and in particular by Met. Liver Chol concentration was significantly higher in all the Se-supplemented C and M groups than in groups C15 and M15. Plasma Chol was, however, lowered. The uninfluenced expression of sterol-regulatory element-binding protein 2 and of hydroxymethyl-glutaryl-CoA reductase, the increased LDL receptor expression and the reduced expression of the hepatobiliary Chol exporter ATP-binding-cassette-transporter 8 (ABCG8) by Se and/or Met explain these findings. We conclude that the elevation of plasma HCys in rats by Se and Met results from a higher export into plasma. The fact that Se in particular combined with Met increases liver Chol but reduces plasma Chol should be addressed in future investigations focussing on the regulation of ABCG8, which is also selectively involved in the reverse transport of phytosterols in the small intestine.

(Received November 03 2009)

(Revised February 15 2010)

(Accepted February 16 2010)

(Online publication March 30 2010)