Towards nutrigenomics: studies to identify gene-diet interactions affecting susceptibility to cardiovascular disease. The FASEB Journal, April 2014; Brian Bennett1,3; Karen Corbin2,; Tangi Smallwood3,; Annalouise o’Connor2; Steven Zeisel1,4.
1UNC Nutrition Research Institute Kannapolis NC United States; 2UNC Nutrition Research Institute Kannapolis NC United States; 3Department of Genetics University of North Carolina Chapel Hill NC United States; 4 Department of Nutrition University of North Carolina Chapel Hill NC United States.
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.