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Ranges of phenotypic flexibility in healthy subjects

van den Broek, T.J. (author), Bakker, G.C.M. (author), Rubingh, C.M. (author), Bijlsma, S. (author), Stroeve, J.H.M. (author), van Ommen, B. (author), van Erk, M.J. (author), Wopereis, S. (author)

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...

article 2017

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

Wopereis, S. (author), Stroeve, J.H.M. (author), Stafleu, A. (author), Bakker, G.C.M. (author), Burggraaf, J. (author), van Erk, M.J. (author), Pellis, L. (author), Boessen, R. (author), Kardinaal, A.A.F. (author), van Ommen, B. (author)

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...

article 2017

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Metabolomic biomarkers for personalised glucose lowering drugs treatment in type 2 diabetes

den Ouden, H. (author), Pellis, L. (author), Rutten, G.E.H.M. (author), Geerars-van Vonderen, I.K. (author), Rubingh, C.M. (author), van Ommen, B. (author), van Erk, M.J. (author), Beulens, J.W.J. (author)

We aimed to identify metabolites to predict patients’ response to glucose lowering treatment during the first 5 years after detection of type 2 diabetes. Metabolites were measured by GC–MS in baseline samples from 346 screen-detected type 2 diabetes patients in the ADDITION-NL study. The response to treatment with metformin and/or sulphonylurea ...

article 2016

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Quantifying phenotypic flexibility as the response to a high-fat challenge test in different states of metabolic health

Kardinaal, A.F.M. (author), van Erk, M.J. (author), Dutman, A.E. (author), Stroeve, J.H.M. (author), van de Steeg, E. (author), Bijlsma, S. (author), Kooistra, T. (author), van Ommen, B. (author), Wopereis, S. (author)

Metabolism maintains homeostasis at chronic hypercaloric conditions, activating postprandial response mechanisms, which come at the cost of adaptation processes such as energy storage, eventually with negative health consequences. This study quantified the metabolic adaptation capacity by studying challenge response curves. After a high-fat...

article 2015

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

Pasman, W.J. (author), van Erk, M.J. (author), Klöpping, W.A.A. (author), Pellis, L. (author), Wopereis, S. (author), Bijlsma, S. (author), Hendriks, H.F.J. (author), Kardinaal, A.F.M. (author)

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...

article 2013

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

Wopereis, S. (author), Wolvers, D. (author), van Erk, M.J. (author), Gribnau, M. (author), Kremer, S.H.A. (author), van Dorsten, F.A. (author), Boelsma, E. (author), Garczarek, U. (author), Cnubben, N. (author), Frenken, L. (author), der Logt P, van (author), Hendriks, H.F. (author), Albers, R. (author), van Duynhoven, J. (author), van Ommen, B. (author), Jacobs, D.M. (author)

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...

article 2013

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

Pellis, L. (author), van Erk, M.J. (author), van Ommen, B. (author), Bakker, G.C.M. (author), Hendriks, H.F.J. (author), Cnubben, N.H.P. (author), Kleemann, R. (author), van Someren, E.P. (author), Bobeldijk, I. (author), Rubingh, C.M. (author), Wopereis, S. (author)

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....

article 2012

document

Moderate alcohol consumption alters both leucocyte gene expression profiles and circulating proteins related to immune response and lipid metabolism in men

Joosten, M.M., (author), van, Erk, M.J. (author), Pellis, L, (author), Witkamp, R.F., (author), Hendriks, H.F. (author)

article 2012

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Perfluoroalkyl sulfonates cause alkyl chain length-dependent hepatic steatosis and hypolipidemia mainly by impairing lipoprotein production in APOE*3-leiden CETP mice

Bijland, S. (author), Rensen, P.C.N. (author), Pieterman, E.J. (author), Maas, A.C.E. (author), van der Hoorn, J.W. (author), van Erk, M.J. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Chang, S.C. (author), Ehresman, D.J. (author), Butenhoff, J.L. (author), Princen, H.M.G. (author)

Perfluorobutane sulfonate (PFBS), perfluorohexane sulfonate (PFHxS), and perfluorooctane sulfonate (PFOS) are stable perfluoroalkyl sulfonate (PFAS) surfactants, and PFHxS and PFOS are frequently detected in human biomonitoring studies. Some epidemiological studies have shown modest positive correlations of serum PFOS with non-high-density...

article 2011

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Anti-inflammatory, anti-proliferative and anti-atherosclerotic effects of quercetin in human in vitro and in vivo models

Kleemann, R. (author), Verschuren, L. (author), Morrison, M. (author), Zadelaar, A.S.M. (author), van Erk, M.J. (author), Wielinga, P.Y. (author), Kooistra, T. (author)

Objective: Polyphenols such as quercetin may exert several beneficial effects, including those resulting from anti-inflammatory activities, but their impact on cardiovascular health is debated. We investigated the effect of quercetin on cardiovascular risk markers including human C-reactive protein (CRP) and on atherosclerosis using transgenic...

article 2011

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Discovery of subtle effects in a human intervention trial through multilevel modeling

Rubingh, C.M. (author), van Erk, M.J. (author), Wopereis, S. (author), van Vliet, T. (author), Verheij, E.R. (author), Cnubben, N.H.P. (author), van Ommen, B. (author), van der Greef, J. (author), Hendriks, H.F.J. (author), Smilde, A.K. (author)

Many benefits can be gained if multi-factorial diseases with a high incidence and prevalence are better understood. Sophisticated approaches like multilevel analyses are needed to discover subtle differences between healthy people and people at the onset of disease in these types of studies. Multilevel analysis generates different sub-models for...

article 2011

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

van Erk, M.J. (author), Wopereis, S. (author), Rubingh, C. (author), van Vliet, T. (author), Verheij, E. (author), Cnubben, N.H. (author), Pedersen, T.L. (author), Newman, J.W. (author), Smilde, A.K. (author), Greef, J.V.D. (author), Hendriks, H.F. (author), van Ommen, B. (author), TNO Kwaliteit van Leven (author)

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...

article 2010

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An antiinflammatory dietary mix modulates inflammation and oxidative and metabolic stress in overweight men: A nutrigenomics approach

Bakker, G.C.M. (author), van Erk, M.J. (author), Pellis, L. (author), Wopereis, S. (author), Rubingh, C.M. (author), Cnubben, N.H.P. (author), Kooistra, T. (author), van Ommen, B. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)

Background: Low-grade chronic inflammation in overweight subjects is thought to play an important role in disease development. Objective: It was hypothesized that specific dietary components are able to reduce low-grade inflammation as well as metabolic and oxidative stress. Design: Dietary products [resveratrol, green tea extract, α-tocopherol,...

article 2010

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Fenofibrate increases very low density lipoprotein triglyceride production despite reducing plasma triglyceride levels in APOE*3-Leiden.CETP mice

TNO Kwaliteit van Leven (author), Bijland, S. (author), Pieterman, E.J. (author), Maas, A.C.E. (author), van der Hoorn, J.W.A. (author), van Erk, M.J. (author), van Klinken, J.B. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author)

The peroxisome proliferator-activated receptor alpha (PPARalpha) activator fenofibrate efficiently decreases plasma triglycerides (TG), which is generally attributed to enhanced very low density lipoprotein (VLDL)-TG clearance and decreased VLDL-TG production. However, because data on the effect of fenofibrate on VLDL production are...

article 2010

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Matrix correlations for high-dimensional data: The modified RV-coefficient

Smilde, A.K. (author), Kiers, H.A.L. (author), Bijlsma, S. (author), Rubingh, C.M. (author), van Erk, M.J. (author), TNO Kwaliteit van Leven (author)

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...

article 2009

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Effect of body fat distribution on the transcription response to dietary fat interventions

TNO Kwaliteit van Leven (author), Radonjic, M. (author), van Erk, M.J. (author), Pasman, W.J. (author), Wortelboer, H.M. (author), Hendriks, H.F.J. (author), van Ommen, B. (author)

Combination of decreased energy expenditure and increased food intake results in fat accumulation either in the abdominal site (upper body obesity, UBO) or on the hips (lower body obesity, LBO). In this study, we used microarray gene expression profiling of adipose tissue biopsies to investigate the effect of body fat distribution on the...

article 2009

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Metabolic profiling of the response to an oral glucose tolerance test detects subtle metabolic changes.

TNO Kwaliteit van Leven (author), Wopereis, S. (author), de Rubingh, C.M. (author), van Erk, M.J. (author), Verheij, E.R. (author), van Vliet, T. (author), Cnubben, N.H. (author), Smilde, A.K. (author), van der Greef, J. (author), van Ommen, B. (author), Hendriks, H.F. (author)

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...

article 2009

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Genome-wide mRNA expression analysis of hepatic adaptation to high-fat diets reveals switch from an inflammatory to steatotic transcriptional program

TNO Kwaliteit van Leven (author), Radonjic, M. (author), de Haan, J.R. (author), van Erk, M.J. (author), van Dijk, K.W. (author), van den Berg, S.A.A. (author), Groot, P.J.de (author), Müller, M. (author), van Ommen, B. (author)

Background: Excessive exposure to dietary fats is an important factor in the initiation of obesity and metabolic syndrome associated pathologies. The cellular processes associated with the onset and progression of diet-induced metabolic syndrome are insufficiently understood. Principal Findings: To identify the mechanisms underlying the...

article 2009

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Short-term fatty acid intervention elicits differential gene expression responses in adipose tissue from lean and overweight men

TNO Kwaliteit van Leven (author), van Erk, M.J. (author), Pasman, W.J. (author), Wortelboer, H.M. (author), van Ommen, B. (author), Hendriks, H.F.J. (author)

The goal of this study was to investigate the effect of a short-term nutritional intervention on gene expression in adipose tissue from lean and overweight subjects. Gene expression profiles were measured after consumption of an intervention spread (increased levels of polyunsaturated fatty acids, conjugated linoleic acid and medium chain...

article 2008

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Pathway and single gene analyses of inhibited Caco-2 differentiation by ascorbate-stabilized quercetin suggest enhancement of cellular processes associated with development of colon cancer

Dihal, A.A. (author), Tilburgs, C. (author), van Erk, M.J. (author), Rietjens, I.M.C.M. (author), Woutersen, R.A. (author), Stierum, R.H. (author), TNO Kwaliteit van Leven (author)

The aim was to investigate mechanisms contributing to quercetin's previously described effects on cell-proliferation and -differentiation, which contradicted its proposed anticarcinogenic potency. In a 10-day experiment, 40 μM quercetin stabilized by 1 mM ascorbate reduced Caco-2 differentiation up to 50% (p < 0.001). Caco-2 RNA from days 5 and...

article 2007