Ranges of phenotypic flexibility in healthy subjects.

BACKGROUND: A key feature of metabolic health is the ability to adapt upon dietary perturbations. A systemic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of metabolic health. Furthermore, it was demonstrated that quantification of PFT response was more sensitive as compared to fasting markers in demonstrating reduced phenotypic flexibility in metabolically impaired type 2 diabetes subjects. METHODS: This study aims to demonstrate that quantification of PFT response can discriminate between different states of health within the healthy range of the population. Therefore, 100 healthy subjects were enrolled (50 males, 50 females) ranging in age (young, middle, old) and body fat percentage (low, medium, high), assuming variation in phenotypic flexibility. Biomarkers were selected to quantify main processes which characterize phenotypic flexibility in response to PFT: flexibility in glucose, lipid, amino acid and vitamin metabolism, and metabolic stress. Individual phenotypic flexibility was visualized using the "health space" by representing the four processes on the health space axes. By quantifying and presenting the study subjects in this space, individual phenotypic flexibility was visualized. RESULTS: Using the "health space" visualization, differences between groups as well as within groups from the healthy range of the population can be easily and intuitively assessed. The health space showed a different adaptation to the metabolic PhenFlex test in the extremes of the recruited population; persons of young age with low to normal fat percentage had a markedly different position in the health space as compared to persons from old age with normal to high fat percentage. CONCLUSION: The results of the metabolic PhenFlex test in conjunction with the health space reliably assessed health on an individual basis. This quantification can be used in the future for personalized health quantification and advice.

Nutrigenomics approach elucidates health-promoting effects of high vegetable intake in lean and obese men.

We aimed to explore whether vegetable consumption according to guidelines has beneficial health effects determined with classical biomarkers and nutrigenomics technologies. Fifteen lean (age 36 ± 7 years; BMI 23.4 ± 1.7 kg m(-2)) and 17 obese (age 40 ± 6 years; BMI 30.3 ± 2.4 kg m(-2)) men consumed 50- or 200-g vegetables for 4 weeks in a randomized, crossover trial. Afterward, all subjects underwent 4 weeks of energy restriction (60 % of normal energy intake). Despite the limited weight loss of 1.7 ± 2.4 kg for the lean and 2.1 ± 1.9 kg for the obese due to energy restriction, beneficial health effects were found, including lower total cholesterol, LDL cholesterol and HbA1c concentrations. The high vegetable intake resulted in increased levels of plasma amino acid metabolites, decreased levels of 9-HODE and prostaglandin D3 and decreased levels of ASAT and ALP compared to low vegetable intake. Adipose tissue gene expression changes in response to vegetable intake were identified, and sets of selected genes were submitted to network analysis. The network of inflammation genes illustrated a central role for NFkB in (adipose tissue) modulation of inflammation by increased vegetable intake, in lean as well as obese subjects. In obese subjects, high vegetable intake also resulted in changes related to energy metabolism, adhesion and inflammation. By inclusion of sensitive omics technologies and comparing the changes induced by high vegetable intake with changes induced by energy restriction, it has been shown that part of vegetables' health benefits are mediated by changes in energy metabolism, inflammatory processes and oxidative stress.

Matrix correlations for high-dimensional data: the modified RV-coefficient.

MOTIVATION: Modern functional genomics generates high-dimensional datasets. It is often convenient to have a single simple number characterizing the relationship between pairs of such high-dimensional datasets in a comprehensive way. Matrix correlations are such numbers and are appealing since they can be interpreted in the same way as Pearson's correlations familiar to biologists. The high-dimensionality of functional genomics data is, however, problematic for existing matrix correlations. The motivation of this article is 2-fold: (i) we introduce the idea of matrix correlations to the bioinformatics community and (ii) we give an improvement of the most promising matrix correlation coefficient (the RV-coefficient) circumventing the problems of high-dimensional data. RESULTS: The modified RV-coefficient can be used in high-dimensional data analysis studies as an easy measure of common information of two datasets. This is shown by theoretical arguments, simulations and applications to two real-life examples from functional genomics, i.e. a transcriptomics and metabolomics example. AVAILABILITY: The Matlab m-files of the methods presented can be downloaded from http://www.bdagroup.nl.

Expression profiling of colon cancer cell lines and colon biopsies: towards a screening system for potential cancer-preventive compounds.

Interest in mechanisms of colon cancer prevention by food compounds is strong and research in this area is often performed with cultured colon cancer cells. In order to assess utility for screening of potential cancer-preventive (food) compounds, expression profiles of 14 human cell lines derived from colonic tissue were measured using cDNA microarrays with 4000 genes and compared with expression profiles in biopsies of human colon tumours and normal tissue. Differences and similarities in the gene expression profiles of the cell lines were analysed by clustering and principal component analysis (PCA). Cytoskeleton genes and immune response genes are two functional classes of genes that contributed to the differences between the cell lines. A subset of 72 colon cancer-specific genes was identified by comparing expression profiles in human colon biopsies of tumour tissue and normal tissue. A separation of the cell lines based on the tumour stage of the original adenocarcinoma was observed after PCA of expression data of the subset of colon cancer-specific genes in the cell lines. The results of this study may be useful in the ongoing research into mechanisms of cancer prevention by dietary components.

Do aberrant crypt foci have predictive value for the occurrence of colorectal tumours? Potential of gene expression profiling in tumours.

The effects of different dietary compounds on the formation of aberrant crypt foci (ACF) and colorectal tumours and on the expression of a selection of genes were studied in rats. Azoxymethane-treated male F344 rats were fed either a control diet or a diet containing 10% wheat bran (WB), 0.2% curcumin (CUR), 4% rutin (RUT) or 0.04% benzyl isothiocyanate (BIT) for 8 months. ACF were counted after 7, 15 and 26 weeks. Tumours were scored after 26 weeks and 8 months. We found that the WB and CUR diets inhibited the development of colorectal tumours. In contrast, the RUT and BIT diets rather enhanced (although not statistically significantly) colorectal carcinogenesis. In addition, the various compounds caused different effects on the development of ACF. In most cases the number or size of ACF was not predictive for the ultimate tumour yield. The expression of some tumour-related genes was significantly different in tumours from the control group as compared to tumours from the treated groups. It was concluded that WB and CUR, as opposed to RUT and BIT, protects against colorectal cancer and that ACF are unsuitable as biomarker for colorectal cancer. Effects of the different dietary compounds on metalloproteinase 1 (TIMP-1) expression correlated well with the effects of the dietary compounds on the ultimate tumour yield.

Arginine intake and risk of coronary heart disease mortality in elderly men.

From experimental studies, the hypothesis is derived that the amino acid arginine, the precursor of NO, could restore the impaired endothelial function and increased platelet activation observed in atherosclerosis. We investigated whether dietary intake of arginine is associated with reduced coronary heart disease risk in elderly persons. The study population consisted of 806 men aged 64 to 84 years at baseline who participated in the Zutphen Elderly Study, a population-based cohort followed up for 10 years. Information about habitual food consumption was collected by use of the cross-check dietary history method. Ninety (11.2%) of the 806 men died from coronary heart disease. Mean+/-SD baseline arginine intake was 4. 35+/-1.07 g/d. Meat was the main source of arginine intake (37.1%), followed by bread (13.1%) and milk and milk products (12.1%). Arginine intake was not associated with coronary heart disease mortality. After adjustment for age, the relative risk (RR) for the medium tertile of arginine intake was 0.72 (95% CI 0.44 to 1.18), and the RR for the highest tertile was 0.71 (95% CI 0.43 to 1.19, P: for trend=0.19) compared with the lowest tertile of arginine intake. After additional adjustment for history of coronary heart disease and diabetes mellitus, energy intake, body mass index, smoking habit, physical activity, and other relevant dietary and biological risk factors, the RR was 1.86 (95% CI 1.06 to 3.27) for the medium intake and 1.56 (95% CI 0.83 to 2.93) for the highest intake (P: for trend=0.17). These results do not support the hypothesis that dietary arginine intake lowers the risk of coronary heart disease mortality.