Dietary methionine effects on plasma homocysteine and HDL metabolism in mice.
The effects of dietary manipulation of folate and methionine on plasma homocysteine (Hcy) 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 Hcy rose to 23 microM on a low-folate/high-methionine diet, but high folate ameliorated the effect of high methionine on fasted plasma Hcy to approximately 10 microM. Determination of nonfasted plasma Hcy levels at 6-h intervals revealed a large diurnal variation in Hcy consistent with a nocturnal lifestyle. The daily average of nonfasted Hcy 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 Hcy 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 Hcy levels of >60 microM, 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.
Velez-Carrasco
Wanda
W
Department of Biochemical Genetics and Metabolism, Rockefeller University, New York, NY 10021, USA.
Merkel
Martin
M
Twiss
Christian O
CO
Smith
Jonathan D
JD
D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency; D008076:Cholesterol, HDL / Q000097:blood; D004032:Diet; D006710:Homocysteine / Q000097:blood* / Q000187:drug effects; D008075:Lipoproteins, HDL / Q000378:metabolism*; D008297:Male; D008715:Methionine / Q000008:administration & dosage / Q000494:pharmacology*; D051379:Mice; D008810:Mice, Inbred C57BL
D001057:Apolipoproteins E; D008076:Cholesterol, HDL; D008075:Lipoproteins, HDL; D006710:Homocysteine; D008715:Methionine
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