Epigenetic Changes with Dietary Soy in Cynomolgus Monkeys

Center for Genomics and Personalized Medicine Research, Wake Forest School of Medicine, Winston-Salem, North Carolina, United States of America.
PLoS ONE (Impact Factor: 3.23). 10/2011; 6(10):e26791. DOI: 10.1371/journal.pone.0026791
Source: PubMed


Nutritional interventions are important alternatives for reducing the prevalence of many chronic diseases. Soy is a good source of protein that contains isoflavones, including genistein and daidzein, and may alter the risk of obesity, Type 2 diabetes, osteoporosis, cardiovascular disease, and reproductive cancers. We have shown previously in nonhuman primates that soy protein containing isoflavones leads to improved body weight, insulin sensitivity, lipid profiles, and atherosclerosis compared to protein without soy isoflavones (casein), and does not increase the risk of cancer. Since genistein has been shown to alter DNA methylation, we compared the methylation profiles of cynomolgus monkeys, from multiple tissues, eating two high-fat, typical American diets (TAD) with similar macronutrient contents, with or without soy protein. DNA methylation status was successfully determined for 80.6% of the probes in at least one tissue using Illumina's HumanMethylation27 BeadChip. Overall methylation increased in liver and muscle tissue when monkeys switched from the TAD-soy to the TAD-casein diets. Genes involved in epigenetic processes, specifically homeobox genes (HOXA5, HOXA11, and HOXB1), and ABCG5 were among those that changed between diets. These data support the use of the HumanMethylation27 BeadChip in cynomolgus monkeys and identify epigenetic changes associated with dietary interventions with soy protein that may potentially affect the etiology of complex diseases.

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    • "In addition to the aforementioned rodent studies, the effects of soy have been studied in monkeys and in vitro. Dietary soy is associated with epigenetic changes in monkeys such that overall methylation in liver and muscle tissue was increased when switching from a soy-based to casein-based diet (51). At high doses, genistein and daidzein are toxic to primary neuronal cultures (52). "
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    • "). The use of a precursor to the Infinium 450K array, the Infinium 27K array, with Cynomolgus macaque tissues has been previously reported (Howard et al. 2011). However, the authors did not test its accuracy for this cross-species use. "
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    • "Indeed, minor diet-induced DNA methylation changes of 3–6% of the NR3C1 gene have been linked to hyperhomocysteinemia in cardiovascular disease [60]. In a soy diet study in monkeys, it was observed that diet-specific DNA methylation changes may vary between the tissue: most pronounced DNA methylation effects were found in liver and muscle, whereas blood remained unaffected [61], [62]. As such, blood samples may not represent the most sensitive tissue to evaluate specific nutritional epigenetic changes. "
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