Dietary methionine effects on plasma homocysteine and HDL metabolism in mice

The effects of dietary manipulation of folate and methionine on plasma homocysteine (Hey) and high-density lipoprotein cholesterol (HDL-C) levels in wild-type and apolipoprotein-E-deficient mice were determined. A low-folate diet with or without folate and/or methionine supplementation in drinking water was administered for 7 weeks. Fasted Hey rose to 23 mu M on a low-folate/high-methionine diet, but high folate ameliorated the effect of high methionine on fasted plasma Hey to similar to 10 mu M. Determination of nonfasted plasma Hey levels at 6-h intervals revealed a large diurnal variation in Hey consistent with a nocturnal lifestyle. The daily average of nonfasted Hey levels was higher than fasted values for high-methionine diets but lower than fasted values for low-methionine diets. An acute methionine load by gavage of fasted mice increased plasma Hey 2.5 h later, but mice that had been on high-methionine diets had a lower fold induction. Mice fed high-methionine diets weighed less than mice fed low-methionine diets. Based on these results, two solid-food diets were developed: one containing 2% added methionine and the other containing 2% added glycine. The methionine diet led to fasted plasma Hey levels of >60 mu M, higher than those with methionine supplementation in drinking water. Mice on methionine diets had >20% decreased body weights and decreased HDL-C levels. An HDL turnover study demonstrated that the HDL-C production rate was significantly reduced in mice fed the methionine diet. (C) 2008 Elsevier Inc. All rights reserved.