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Multi-parameter comparison of a standardized mixed meal tolerance test in healthy and type 2 diabetic subjects: the PhenFlex challenge

Background A key feature of metabolic health is the ability to adapt upon dietary perturbations. Recently, it was shown that metabolic challenge tests in combination with the new generation biomarkers allow the simultaneous quantification of major metabolic health processes. Currently, applied challenge tests are largely non-standardized. A systematic review defined an optimal...

The Network Library: a framework to rapidly integrate network biology resources

Motivation: Much of the biological knowledge accumulated over the last decades is stored in different databases governed by various organizations and institutes. Integrating and connecting these vast knowledge repositories is an extremely useful method to support life sciences research and help formulate novel hypotheses. Results: We developed the Network Library (NL), a...

The impact of micronutrient status on health: correlation network analysis to understand the role of micronutrients in metabolic-inflammatory processes regulating homeostasis and phenotypic flexibility

Background Vitamins and carotenoids are key micronutrients facilitating the maintenance of health, as evidenced by the increased risk of disease with low intake. Optimal phenotypic flexibility, i.e., the ability to respond to a physiological challenge, is an essential indicator of health status. Therefore, health can be measured by applying a challenge test and monitoring the...

Phenotypic flexibility as a measure of health: the optimal nutritional stress response test

Suzan Wopereis 0 1 0 TNO , PO Box 360, 3700 AJ Zeist , The Netherlands 1 This article is part of a Topical Collection in Genes and Nutrition on ''Systems Nutrition and Health,'' guest edited by Jim Kaput

Controlling false discovery rates in factorial experiments with between-subjects and within-subjects tests

Background The False Discovery Rate (FDR) controls the expected number of false positives among the positive test results. It is not straightforward how to conduct a FDR controlling procedure in experiments with a factorial structure, while at the same time there are between-subjects and within-subjects factors. This is because there are P-values for different tests in one and...

Visualization and identification of health space, based on personalized molecular phenotype and treatment response to relevant underlying biological processes

Jildau Bouwman Jack TWE Vogels Suzan Wopereis Carina M Rubingh Sabina Bijlsma Ben van Ommen Background: Being able to visualize multivariate biological treatment effects can be insightful. However

Differential Effects of Drug Interventions and Dietary Lifestyle in Developing Type 2 Diabetes and Complications: A Systems Biology Analysis in LDLr−/− Mice

Excess caloric intake leads to metabolic overload and is associated with development of type 2 diabetes (T2DM). Current disease management concentrates on risk factors of the disease such as blood glucose, however with limited success. We hypothesize that normalizing blood glucose levels by itself is insufficient to reduce the development of T2DM and complications, and that...

Assessment of inflammatory resilience in healthy subjects using dietary lipid and glucose challenges

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...

Plasma metabolomics and proteomics profiling after a postprandial challenge reveal subtle diet effects on human metabolic status

We introduce the metabolomics and proteomics based Postprandial Challenge Test (PCT) to quantify the postprandial response of multiple metabolic processes in humans in a standardized manner. The PCT comprised consumption of a standardized 500 ml dairy shake containing respectively 59, 30 and 12 energy percent lipids, carbohydrates and protein. During a 6 h time course after PCT...

Plasma and Liver Lipidomics Response to an Intervention of Rimonabant in ApoE*3Leiden.CETP Transgenic Mice

Suzan Wopereis Louis M. Havekes Elwin Verheij Thomas Hankemeier Guowang Xu Jan van der Greef Matej Oresic, Governmental Technical Research Centre of Finland, Finland Background: Lipids are known to play

Mass-spectrometry-based metabolomics: limitations and recommendations for future progress with particular focus on nutrition research

Mass spectrometry (MS) techniques, because of their sensitivity and selectivity, have become methods of choice to characterize the human metabolome and MS-based metabolomics is increasingly used to characterize the complex metabolic effects of nutrients or foods. However progress is still hampered by many unsolved problems and most notably the lack of well established and...

Improving the analysis of designed studies by combining statistical modelling with study design information

Background In the fields of life sciences, so-called designed studies are used for studying complex biological systems. The data derived from these studies comply with a study design aimed at generating relevant information while diminishing unwanted variation (noise). Knowledge about the study design can be used to decompose the total data into data blocks that are associated...

Lipidomics Reveals Multiple Pathway Effects of a Multi-Components Preparation on Lipid Biochemistry in ApoE*3Leiden.CETP 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...

Insight in modulation of inflammation in response to diclofenac intervention: a human intervention study

Background Chronic systemic low-grade inflammation in obese subjects is associated with health complications including cardiovascular diseases, insulin resistance and diabetes. Reducing inflammatory responses may reduce these risks. However, available markers of inflammatory status inadequately describe the complexity of metabolic responses to mild anti-inflammatory therapy...

Time-Resolved and Tissue-Specific Systems Analysis of the Pathogenesis of Insulin Resistance

Background The sequence of events leading to the development of insulin resistance (IR) as well as the underlying pathophysiological mechanisms are incompletely understood. As reductionist approaches have been largely unsuccessful in providing an understanding of the pathogenesis of IR, there is a need for an integrative, time-resolved approach to elucidate the development of the...

Patients with unsolved congenital disorders of glycosylation type II can be subdivided in six distinct biochemical groups

Defects in the biosynthesis of N- and core 1 O-glycans may be found by isoelectric focusing (IEF) of plasma transferrin and apolipoprotein C-III (apoC-III). We hypothesized that IEF of transferrin and apoC-III in combination with sodium dodecyl sulphate–polyacrylamide gel electrophoresis (SDS–PAGE) of apoC-III may provide a classification for congenital disorders of glycosylation...

Metabolic Profiling of the Response to an Oral Glucose Tolerance Test Detects Subtle Metabolic Changes

Background The prevalence of overweight is increasing globally and has become a serious health problem. Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Novel tools to understand these processes are needed. Metabolic profiling is one such tool that can provide novel insights into the impact of treatments on...

The Micronutrient Genomics Project: a community-driven knowledge base for micronutrient research

Micronutrients influence multiple metabolic pathways including oxidative and inflammatory processes. Optimum micronutrient supply is important for the maintenance of homeostasis in metabolism and, ultimately, for maintaining good health. With advances in systems biology and genomics technologies, it is becoming feasible to assess the activity of single and multiple micronutrients...

Challenges of molecular nutrition research 6: the nutritional phenotype database to store, share and evaluate nutritional systems biology studies

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...