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Towards nutrigenomics: studies to identify gene‐diet interactions affecting susceptibility to cardiovascular disease (373.4)
Author(s) -
Bennett Brian,
Corbin Karen,
Smallwood Tangi,
O'Connor annalouise,
Zeisel Steven
Publication year - 2014
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.28.1_supplement.373.4
Subject(s) - nutrigenomics , metabolomics , biology , computational biology , betaine , disease , trimethylamine n oxide , genetics , bioinformatics , gene , medicine , biochemistry , trimethylamine
Science has been revolutionized by the advent of high‐throughput technologies of the ‐omic scale. Nutrigenomics aims to identify genetic and dietary interactions that affect gene expression. A goal of nutrigenomics is to identify novel gene x diet interactions that increase susceptibility to disease. Nutrigenomics approaches can incorporate multiple scales of data, such as mRNA and metabolite levels, to identify these novel interactions. One scale of data that is particularly promising for nutrigenomic studies is metabolomics, system‐wide study of small molecule metabolites. An example of the utility of metabolomics are the recent studies identifying specific choline metabolites as predictive of cardiovascular disease. In particular, circulating levels of the trimethylamine N‐oxide (TMAO) and betaine are associated with increased atherosclerosis in humans and mice. Our current research is aimed at developing a nutrigenomic platform. To accomplish this, we employ a systems‐genetic approach to elucidate the genetic and dietary factors affecting cardiovascular susceptibility. We have initiated a set of studies across genetically diverse mouse strains to understand basal and diet‐induced changes in choline metabolism, focused on TMAO and betaine metabolism. Initial results thus far demonstrate that choline metabolites vary by genetic background, are affected by diet and that dietary challenges elicit a genetic x diet interaction that may involve the microbiome. We have extended these studies using the Diversity Outbred (DO) mouse panel recently developed by the Jackson Laboratory to identify a novel locus regulating TMAO levels in mice. Overall, these studies offer a proof a principle for an approach to nutrigenomic studies. Grant Funding Source : Pilot funds from the Nutrition Obesity Research Center (P30DK056350) and the NHLBI (4R00HL102223)