Homocysteine thiolactone-induced hyperhomocysteinemia does not alter concentrations of cholesterol and SREBP-2 target gene mRNAS in rats.

The present rat study was conducted to test whether hyper-homocysteinemia induced by dietary homocysteine (Hcy) alters the cholesterol concentration in plasma and tissue and the gene expression of genes involved in cholesterol biosynthesis and uptake. Therefore, rats were fed 100 or 200 mg Hcy per kilogram body mass per day (Hcy100 group and Hcy200 group, respectively) as dl-homocysteine thiolactone, or an Hcy-free diet, which served as control, over 14 days. Rats from the Hcy100 group and the Hcy200 group had higher plasma Hcy concentrations (34.4 +/- 4.6 and 69.4 +/- 11.5 microM, respectively) than rats fed an Hcy-free diet (9.5 +/- 1.7 microM). The concentration of Hcy in liver was 2.6 and 3.8 times higher, and in small intestine was 2.6 and 5.1 times higher, in the Hcy100 group and the Hcy200 group, respectively, than in control rats (P < 0.05). The concentrations of cholesterol in plasma, lipoproteins, liver, and small intestine and the relative mRNA concentrations of sterol regulatory element-binding protein 2 (SREBP-2), 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase, and low-density lipoprotein (LDL) receptor in liver and small intestine were not influenced by dl-homocysteine thiolactone supplementation. In conclusion, in view of the experimental conditions used here, increased plasma and tissue concentrations of Hcy do not alter cholesterol metabolism of liver and intestine.