Homocysteine homeostasis in the rat is maintained by compensatory changes in cystathionine β-synthase, betaine-homocysteine methyltransferase, and phosphatidylethanolamine N-methyltransferase gene transcription occurring in response to maternal protein and folic acid intake during pregnancy and fat intake after weaning ☆ Agata Chmurzynska ⁎ , Anna M. Malinowska Department of Human Nutrition and Hygiene, Poznań University of Life Sciences Wojska Polskiego 31, 60-624 Poznań Received 6 April 2011; revised 29 June 2011; accepted 1 July 2011 Abstract The reactions of the methionine/homocysteine pathway are mediated by several enzymes, including phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine- homocysteine methyltransferase. Homocysteine homeostasis is regulated by these enzymes. We hypothesized here that the protein and folic acid content in the maternal diet affects methionine/ homocysteine metabolism in the progeny. To test this hypothesis, pregnant rats were fed a diet with normal protein and normal folic acid levels (a modified casein-based AIN-93G diet), a protein- restricted and normal folic acid diet, a protein-restricted and folic acid–supplemented diet, or a normal protein and folic acid–supplemented diet. The progeny were fed either the modified AIN- 93G diet or a high-fat lard-based diet. Progeny were analyzed for expression of the phosphatidylethanolamine N-methyltransferase, cystathionine β-synthase, and betaine-homocysteine methyltransferase genes in the liver and for serum homocysteine concentration. Interactions between prenatal and postnatal nutrition were also determined. The progeny of the dams fed the diets supplemented with folic acid showed decreased expression of all 3 genes (P b .001). An interaction effect between the protein and folic acid content in the maternal diet contributed to this down- regulation (P b .001), and the postweaning diet modified these effects. Serum homocysteine concentrations were approximately 15% higher in the male rats (P b .01), but neither prenatal nutrition nor the postweaning diet affected it significantly. We conclude that maternal diet during gestation has an important effect on the transcription level of these 3 genes, but changes in gene expression were not associated with significant changes in progeny homocysteine concentrations. © 2011 Elsevier Inc. All rights reserved. Keywords: Fetal programming; Homocysteine; CBS; BHMT; PEMT; Rats Abbreviations: 18S rRNA, 18S ribosomal RNA; ACTB, β-actin; BHMT, betaine-homocysteine methyltransferase; CBS, cystathionine β-synthase; HF, high-fat diet; NP-FS, normal protein diet, supplemented with folic acid; NP-NF, normal protein diet, with normal folic acid levels; PR-FS, protein-restricted diet, supplemented with folic-acid; PR- NF, protein-restricted diet, with normal folic acid levels; PEMT, phosphatidylethanolamine N-methyltransferase. Available online at www.sciencedirect.com Nutrition Research 31 (2011) 572 – 578 www.nrjournal.com ☆ This study was supported by the Polish Ministry of Education and Science (grant no. N N312 151034). ⁎ Corresponding author. Tel.: +48 61 848 73 33; fax: +48 61 848 73 32. E-mail address: agata@jay.up.poznan.pl (A. Chmurzynska). 0271-5317/$ – see front matter © 2011 Elsevier Inc. All rights reserved. doi:10.1016/j.nutres.2011.07.001