Nutrient-gene interaction: metabolic genotype-phenotype relationship.

Department of Medicine, David Geffen School of Medicine at UCLA, University of California-Los Angeles, CA 90095, USA.
Journal of Nutrition (Impact Factor: 3.88). 01/2006; 135(12 Suppl):3016S-3020S.
Source: PubMed


The U.S. Department of Health and Human Services (DHHS)/USDA Dietary Guidelines for Americans is a science and population evidence-based guide on diet and physical activity, providing advice and recommendations to promote a healthier lifestyle and reduce the risk of chronic diseases, including cancer. These recommendations are supported by the comprehensive evidence-based review on diet and cancer prevention conducted by the American Institute for Cancer Research, National Cancer Institute, World Health Organization/International Agency for Research on Cancer, and others. However, influencing dietary effects are the individual genetic predispositions that are the basis for considerable interindividual variations in cancer risk within the population and in nutrient homeostasis, which is maintained by genomic-nutrient and metabolic-phenotype interactions. Although genetics is an important component, it accounts for only a portion of this variation. An individual's overall phenotype, including health status, is achieved and maintained by the sum of metabolic activities functioning under differing circumstances within the life cycle and the complex interactions among genotype, metabolic phenotype, and the environment. In this postgenomic era, high-throughput groups of technologies in genomics, proteomics, and metabolomics measure and analyze DNA sequences, RNA transcripts, proteins, and nutrient-metabolic fluxes in a single experiment. These advances have transformed biomarker studies on nutrient-gene interactions from a reductionist concept into a holistic practice in which many regulated genes involved in metabolism, along with its metabolic phenotypes, can be measured through functional genomics and metabolic profiling. The overall integration of data and information from the building blocks of metabolism-based nutrient-gene interaction can lead to future individualized dietary recommendations to diminish cancer risk.

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    • "Therefore, to move from current population based dietary guidelines into personalised nutritional advice, responses to dietary challenges need to be investigated with an emphasis on differential response. Such research could provide insight into metabolic status based on nutrient-specific responses [2]. The term metabotype has emerged in the literature and it defines a metabolic phenotype that classifies an individual in a particular category. "
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    ABSTRACT: In recent years an individual's ability to respond to an acute dietary challenge has emerged as a measure of their biological flexibility. Analysis of such responses has been proposed to be an indicator of health status. However, for this to be fully realised further work on differential responses to nutritional challenge is needed. This study examined whether metabolic phenotyping could identify differential responders to an oral glucose tolerance test (OGTT) and examined the phenotypic basis of the response. A total of 214 individuals were recruited and underwent challenge tests in the form of an OGTT and an oral lipid tolerance test (OLTT). Detailed biochemical parameters, body composition and fitness tests were recorded. Mixed model clustering was employed to define 4 metabotypes consisting of 4 different responses to an OGTT. Cluster 1 was of particular interest, with this metabotype having the highest BMI, triacylglycerol, hsCRP, c-peptide, insulin and HOMA- IR score and lowest VO2max. Cluster 1 had a reduced beta cell function and a differential response to insulin and c-peptide during an OGTT. Additionally, cluster 1 displayed a differential response to the OLTT. This work demonstrated that there were four distinct metabolic responses to the OGTT. Classification of subjects based on their response curves revealed an "at risk" metabolic phenotype.
    PLoS ONE 08/2013; 8(8):e72890. DOI:10.1371/journal.pone.0072890 · 3.23 Impact Factor
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    • "These in turn increase the risk of diseases such as obesity, type 2 diabetes, hypertension , food allergies and intolerances, and gastrointestinal and inflammatory disorders. Good nutrition is vital for health, optimal growth and development, and prevention of disease [2]. It is now understood that nutrients and other substances obtained from a wide variety of foods promote health, maintain metabolic homeostasis, and fulfill energy requirements. "
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    ABSTRACT: How do functional foods affect human health? To answer this question it is important to understand what happens when food is digested and taken up by the gastrointestinal (GI) tract. The gut is a selective nutrient absorption system and the most important signal transduction and information exchange system within the body. It acts as a signal transducer, a neuroendocrine sensor, and an immunological recognition and presentation system. It is also a complex information exchange system comprising a number of signaling networks involving GI cells and cells immobilized in organs or transported in blood. The bioactivity of functional foods in vivo may be due to their effects on such networks, but this raises the question of what signaling pathways are used by non-nutrients that cannot be absorbed by the gut. The purpose of this review is to describe intestinal nutrient transportation, identify a number of widely expressed receptors and signal transduction pathways, and outline our current understanding of the mechanisms involved in health and disease. At the end of the review, a method for developing a cell communication network is described. This network is convenient for investigating the effects of oral administration of experimental medicines, drugs, or functional foods on cytokines of interest. Because cytokines and chemokines are transported via the circulatory system, a simple 2–3 mL blood sample from a volunteer is a rich source of information. This method may become the gold standard for evaluating the effects of functional foods or medicines in vivo.
    12/2012; 1(1):26–60. DOI:10.1016/j.fshw.2012.10.001
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    • "Epigenomics seek to characterize genes that participate in diet-disease relationships, while Proteomics and Metabolomics involve measuring the protein or metabolite end products of gene expression in response to dietary influences, and can be considered critical measures of function or phenotype (Cobiac, 2007; Go et al., 2005). Microbiome studies represent the youngest of the aforementioned high throughput technologies, and reveals how the phylogenetic make up of our GI tract microbiota may influence overall metabolic status and diet-disease relationships (Hattori, 2009), and emerging models support the importance of gut microbial community modifications by diet (Flint, Duncan, Scott, & Louis, 2007; Kau, Ahern, Griffin, Goodman, & Gordon, 2011; Ley et al., 2005). "

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