Analyzing metabolomics-based challenge tests
Vis, D.J. ; Westerhuis, J.A. ; Jacobs, D.M. ; Duynhoven, J.P.M. van; Wopereis, S. ; Ommen, B. van; Hendriks, M.M.W.B. ; Smilde, A.K. - \ 2015
Metabolomics 11 (2015)1. - ISSN 1573-3882 - p. 50 - 63.
glucose-tolerance test - insulin sensitivity - mathematical-models - component analysis - plasma metabolome - health - asca - reconstruction - phenotype - discovery
Challenge tests are used to assess the resilience of human beings to perturbations by analyzing responses to detect functional abnormalities. Well known examples are allergy tests and glucose tolerance tests. Increasingly, metabolomics analysis of blood or serum samples is used to analyze the biological response of the individual to these challenges. The information content of such metabolomics challenge test data involves both the disturbance and restoration of homeostasis on a metabolic level and is thus inherently different from the analysis of steady state data. It opens doors to study the variation of resilience between individuals beyond the classical biomarkers; preferably in terms of underlying biological processes. We review challenge tests in which metabolomics was used to analyze the biological response. Specifically, we describe strategies to perform statistical analyses on the responses and we will show some examples of these strategies applied to a postprandial challenge that was used to study a diet with anti-inflammatory properties. Finally we discuss open issues and give recommendation for further research.
Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges
Wopereis, S. ; Wolvers, D. ; Erk, M. van; Gribnau, M. ; Kremer, B. ; Dorsten, F.A. van; Boelsma, E. ; Garczarek, U. ; Cnubben, N. ; Frenken, L. ; Logt, P. van der; Hendriks, H.F.J. ; Albers, R. ; Duynhoven, J.P.M. van; Ommen, B. van; Jacobs, D.M. - \ 2013
BMC Medical Genomics 6 (2013). - ISSN 1755-8794 - 16 p.
type-2 diabetic-patients - necrosis-factor-alpha - oxidative stress - endothelial dysfunction - cytokine concentrations - postprandial variations - fatty-acids - obese men - fish-oil - markers
Background Resilience or the ability of our body to cope with daily-life challenges has been proposed as a new definition of health, with restoration of homeostasis as target resultant of various physiological stress responses. Challenge models may thus be a sensitive measure to study the body’s health. The objective of this study was to select a dietary challenge model for the assessment of inflammatory resilience. Meals are a challenge to metabolic homeostasis and are suggested to affect inflammatory pathways, yet data in literature are limited and inconsistent. Method The kinetic responses of three different dietary challenges and a water control challenge were assessed on various metabolic and inflammatory markers in 14 healthy males and females using a full cross-over study design. The dietary challenges included glucose (75 g glucose in 300 ml water), lipids (200 ml whipping cream) and a mix of glucose and lipids (same amounts as above), respectively. Blood samples were collected at baseline and at 0.5, 1, 2, 4, 6, 8 and 10 h after consumption of the treatment products. Inflammation (IFN¿, IL-1ß, IL-6, IL-8, IL-10, IL-12p70, TNF-a CRP, ICAM-1, VCAM-1, SAA, E-selectin, P-selectin, thrombomodulin, leukocytes, neutrophils, lymphocytes) and clinical (e.g. glucose, insulin, triglycerides) markers as well as gene expression in blood cells and plasma oxylipin profiles were measured. Results All three dietary challenges induced changes related to metabolic control such as increases in glucose and insulin after the glucose challenge and increases in triglycerides after the lipid challenge. In addition, differences between the challenges were observed for precursor oxylipins and some downstream metabolites including DiHETrE’s and HODE’s. However, none of the dietary challenges induced an acute inflammatory response, except for a modest increase in circulating leukocyte numbers after the glucose and mix challenges. Furthermore, subtle, yet statistically significant increases in vascular inflammatory markers (sICAM-1 and sVCAM-1) were found after the mix challenge, when compared to the water control challenge. Conclusions This study shows that dietary glucose and lipid challenges did not induce a strong acute inflammatory response in healthy subjects, as quantified by an accurate and broad panel of parameters.
Lipidomics reveals multiple pathway effects of a multi components preparation on lipd biochemistry in ApoeE*3Leiden.CETP mice
Wei, H. ; Hu, C. ; Wang, M. ; Hoek, A.M. van den; Reijmers, T.H. ; Wopereis, S. ; Bouwman, J. ; Ramaker, R. ; Korthout, H.A.A.J. ; Vennik, M. ; Hankemeier, T. ; Havekes, L.M. ; Witkamp, R.F. ; Verheij, E.R. ; Xu, G. ; Greef, J. de - \ 2012
PLoS ONE 7 (2012)1. - ISSN 1932-6203
cholesteryl ester transfer - systems biology - apoe-asterisk-3-leiden.cetp mice - aggravates atherosclerosis - overweight patients - chinese medicine - weight-reduction - transfer protein - hdl-cholesterol - transgenic mice
Background: Causes and consequences of the complex changes in lipids occurring in the metabolic syndrome are only partly understood. Several interconnected processes are deteriorating, which implies that multi-target approaches might be more successful than strategies based on a limited number of surrogate markers. Preparations from Chinese Medicine (CM) systems have been handed down with documented clinical features similar as metabolic syndrome, which might help developing new intervention for metabolic syndrome. The progress in systems biology and specific animal models created possibilities to assess the effects of such preparations. Here we report the plasma and liver lipidomics results of the intervention effects of a preparation SUB885C in apolipoprotein E3 Leiden cholesteryl ester transfer protein (ApoE*3Leiden.CETP) mice. SUB885C was developed according to the principles of CM for treatment of metabolic syndrome. The cannabinoid receptor type 1 blocker rimonabant was included as a general control for the evaluation of weight and metabolic responses. Methodology/Principal Findings: ApoE*3Leiden.CETP mice with mild hypercholesterolemia were divided into SUB885C-, rimonabant- and non-treated control groups. SUB885C caused no weight loss, but significantly reduced plasma cholesterol (-49%, p <0.001), CETP levels (-31%, p
Enhanced catch-up growth after a challenge in animals on organic feed
Huber, M. ; Coulier, L. ; Wopereis, S. ; Savelkoul, H.F.J. ; Nierop, D. ; Hoogenboom, L.A.P. - \ 2012
biologische landbouw - diergezondheid - pluimveehouderij - pluimveevoeding - kippen - kuikens - organic farming - animal health - poultry farming - poultry feeding - fowls - chicks
A feeding experiment was performed in two generations of three groups of chickens with different immune responsiveness. All groups were fed identically composed feeds from either organic or conventional production. In the young animals of the second generation an immune challenge was imposed. The chickens fed conventional feed showed overall a higher weight gain, whereas feed intake of the groups was similar. The animals on organic feed showed an enhanced immune reactivity, a stronger reaction to the immune challenge, as well as an enhanced ’catch-up-growth’ after the challenge.
Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice
Lu, Y. ; Boekschoten, M.V. ; Wopereis, S. ; Muller, M.R. ; Kersten, A.H. - \ 2011
Physiological genomics 43 (2011)23. - ISSN 1094-8341 - p. 1307 - 1318.
activated-receptor-alpha - polyunsaturated fatty-acids - coronary-heart-disease - ppar-alpha - gene-expression - eicosapentaenoic acid - vitamin-k - lipoprotein metabolism - adiponectin secretion - protein expression
Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with fenofibrate or fish oil. To gain insight into underlying mechanisms, we carried out a comparative transcriptomics and metabolomics analysis of the effect of 2 wk treatment with fenofibrate and fish oil in mice. Plasma triglycerides were significantly decreased by fenofibrate (-49.1%) and fish oil (-21.8%), whereas plasma cholesterol was increased by fenofibrate (+29.9%) and decreased by fish oil (-32.8%). Levels of various phospholipid species were specifically decreased by fish oil, while levels of Krebs cycle intermediates were increased specifically by fenofibrate. Plasma levels of many amino acids were altered by fenofibrate and to a lesser extent by fish oil. Both fenofibrate and fish oil upregulated genes involved in fatty acid metabolism and downregulated genes involved in blood coagulation and fibrinolysis. Significant overlap in gene regulation by fenofibrate and fish oil was observed, reflecting their property as high or low affinity agonist for peroxisome proliferator-activated receptor-a, respectively. Fenofibrate specifically downregulated genes involved in complement cascade and inflammatory response. Fish oil specifically downregulated genes involved in cholesterol and fatty acid biosynthesis and upregulated genes involved in amino acid and arachidonic acid metabolism. Taken together, the data indicate that despite being similarly potent toward modulating plasma free fatty acids, cholesterol, and triglyceride levels, fish oil causes modest changes in gene expression likely via activation of multiple mechanistic pathways, whereas fenofibrate causes pronounced gene expression changes via a single pathway, reflecting the key difference between nutritional and pharmacological intervention.
Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies
Ommen, B. van; Bouwman, J.H. ; Dragsted, L.O. ; Drevon, C.A. ; Elliott, R. ; Groot, P.J. de; Kaput, J. ; Mathers, J.C. ; Müller, M.R. ; Pepping, F. ; Saito, J. ; Scalbert, A. ; Radonjic, M. ; Rocca-Serra, P. ; Travis, A. ; Wopereis, S. ; Evelo, C. - \ 2010
Genes & Nutrition 5 (2010)3. - ISSN 1555-8932 - p. 189 - 203.
gene-expression - metabolic phenotypes - association - framework - services - network - complex - health - diet
The challenge of modern nutrition and health research is to identify food-based strategies promoting life-long optimal health and well-being. This research is complex because it exploits a multitude of bioactive compounds acting on an extensive network of interacting processes. Whereas nutrition research can profit enormously from the revolution in ‘omics’ technologies, it has discipline-specific requirements for analytical and bioinformatic procedures. In addition to measurements of the parameters of interest (measures of health), extensive description of the subjects of study and foods or diets consumed is central for describing the nutritional phenotype. We propose and pursue an infrastructural activity of constructing the “Nutritional Phenotype database” (dbNP). When fully developed, dbNP will be a research and collaboration tool and a publicly available data and knowledge repository. Creation and implementation of the dbNP will maximize benefits to the research community by enabling integration and interrogation of data from multiple studies, from different research groups, different countries and different-omics levels. The dbNP is designed to facilitate storage of biologically relevant, pre-processed-omics data, as well as study descriptive and study participant phenotype data. It is also important to enable the combination of this information at different levels (e.g. to facilitate linkage of data describing participant phenotype, genotype and food intake with information on study design and-omics measurements, and to combine all of this with existing knowledge). The biological information stored in the database (i.e. genetics, transcriptomics, proteomics, biomarkers, metabolomics, functional assays, food intake and food composition) is tailored to nutrition research and embedded in an environment of standard procedures and protocols, annotations, modular data-basing, networking and integrated bioinformatics. The dbNP is an evolving enterprise, which is only sustainable if it is accepted and adopted by the wider nutrition and health research community as an open source, pre-competitive and publicly available resource where many partners both can contribute and profit from its developments. We introduce the Nutrigenomics Organisation (NuGO, http://www.nugo.org) as a membership association responsible for establishing and curating the dbNP. Within NuGO, all efforts related to dbNP (i.e. usage, coordination, integration, facilitation and maintenance) will be directed towards a sustainable and federated infrastructure
Effects of organically and conventionally produced feed on biomarkers of health in a chicken model
Huber, M. ; Vijver, L.P.L. van de; Parmentier, H.K. ; Savelkoul, H.F.J. ; Coulier, L. ; Wopereis, S. ; Verheij, E. ; Greef, J. de; Nierop, D. ; Hoogenboom, R.A.P. - \ 2010
The British journal of nutrition 103 (2010)5. - ISSN 0007-1145 - p. 663 - 676.
red-blood-cells - catch-up growth - antibody-responses - natural antibodies - immune-responses - lines - foods - metabolomics - systems - consequences
Consumers expect organic products to be healthier. However, limited research has been performed to study the effect of organic food on health. The present study aimed to identify biomarkers of health to enable future studies in human subjects. A feeding experiment was performed in two generations of three groups of chickens differing in immune responsiveness, which were fed identically composed feeds from either organic or conventional produce. The animals of the second generation were exposed to an immune challenge and sacrificed at 13 weeks of age. Feed and ingredients were analysed on macro- and micronutrients, i.e. vitamins, minerals, trace elements, heavy metals and microbes. The chickens were studied by general health and immune parameters, metabolomics, genomics and post-mortem evaluation. The organic and conventional feeds were comparable with respect to metabolisable energy. On average, the conventionally produced feeds had a 10 % higher protein content and some differences in micronutrients were observed. Although animals on both feeds were healthy, differences between the groups were found. The random control group of chickens fed conventional feed showed overall a higher weight gain during life span than the group on organic feed, although feed intake was mostly comparable. The animals on organic feed showed an enhanced immune reactivity, a stronger reaction to the immune challenge as well as a slightly stronger ‘catch-up growth’ after the challenge. Biomarkers for future research were identified in the parameters feed intake, body weight and growth rate, and in immunological, physiological and metabolic parameters, several of these differing most pronounced after the challenge