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Genistein mediates perturbations in one‐carbon metabolism during diet‐induced folate deficiency
Author(s) -
necke Eric B,
Schalinske Kevin L
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.915.10
Subject(s) - genistein , endocrinology , medicine , epigenome , phytoestrogens , homocysteine , estrogen , dna methylation , hyperhomocysteinemia , methyltransferase , chemistry , biology , methylation , biochemistry , gene expression , dna , gene
Populations consuming isoflavone‐rich diets exhibit lower prevalence of heart disease and estrogen‐responsive cancers. Genistein, a17β‐estradiol‐like isoflavone, has been shown to modify the fetal epigenome in utero in the agouti mouse model and modulate DNA methylation patterns in estrogen‐responsive tissues. Moreover, it also exhibits antiproliferative action in cancerous cells via suppression of S‐adenosylmethionine –dependent DNA methyltransferases, leading to site‐specific hypomethylation. However, it is not known if genistein modulates one‐carbon metabolism, a process that when disrupted leads to dysregulation of the epigenome. The objective of this study was to characterize the metabolic actions of genistein during moderate dietary folate deficiency. Male Sprague Dawley ratswere fed an ad lib control or folate‐deficient (FD) diet with or without genistein supplementation (300 mg/kg diet) for 8 wk. Plasma homocysteine (Hcy) concentrations in genistein‐supplemented, FD animals (16.7 μM) was lower ( P = 0.02) than the Hcy concentration of FD animals not supplemented with genistein (27.9 μM). Hepatic enzyme analysis suggests the ability of genistein to attenuate hyperhomocysteinemia in FD rats is not linked to diminished Hcy production. Clearly, genistein has the ability to modulate Hcy and methyl‐group metabolism; however, the underlying mechanisms remain unknown. Grant Funding Source : AHA assn