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(Pro)Renin Receptor Antagonism Attenuates High-Fat-Diet–Induced Hepatic Steatosis

Gayban, A.J.B. (author), Souza, L.A.C. (author), Cooper, S.G. (author), Regalado, E. (author), Kleemann, R. (author), Earley, Y.F. (author)

Non-alcoholic fatty liver disease (NAFLD) comprises a spectrum of liver damage directly related to diabetes, obesity, and metabolic syndrome. The (pro)renin receptor (PRR) has recently been demonstrated to play a role in glucose and lipid metabolism. Here, we test the hypothesis that the PRR regulates the development of diet-induced hepatic...

article 2023

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The circadian clock, shift work, and tissue-specific insulin resistance

Oosterman, J.E. (author), Wopereis, S. (author), Kalsbeek, A. (author)

Obesity and type 2 diabetes (T2D) have become a global health concern. The prevalence of obesity and T2D is significantly higher in shift workers compared to people working regular hours. An accepted hypothesis is that the increased risk for metabolic health problems arises from aberrantly timed eating behavior, that is, eating out of synchrony...

article 2020

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Actions of metformin and statins on lipid and glucose metabolism and possible benefit of combination therapy

van Stee, M.F. (author), de Graaf, A.A. (author), Groen, A.K. (author)

Patients with diabetes type 2 have an increased risk for cardiovascular disease and commonly use combination therapy consisting of the anti-diabetic drug metformin and a cholesterol-lowering statin. However, both drugs act on glucose and lipid metabolism which could lead to adverse effects when used in combination as compared to monotherapy. In...

article 2018

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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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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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The Netherlands twin register biobank: A resource for genetic epidemiological studies

Willemsen, G. (author), de Geus, E.J.C. (author), Bartels, M. (author), van Beijsterveldt, C.E.M.T. (author), Brooks, A.I. (author), Estourgie-van Burk, G.F. (author), Fugman, D.A. (author), Hoekstra, C. (author), Hottenga, J.-J. (author), Kluft, K. (author), Meijer, P. (author), Montgomery, G.W. (author), Rizzu, P. (author), Sondervan, D. (author), Smit, A.B. (author), Spijker, S. (author), Suchiman, H.E.D. (author), Tischfield, J.A. (author), Lehner, T. (author), Slagboom, P.E. (author), Boomsma, D.I. (author), TNO Kwaliteit van Leven (author)

In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am...

article 2010

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Intracerebroventricular administration of neuropeptide Y induces hepatic insulin resistance via sympathetic innervation

van den Hoek, A.M. (author), van Heijningen, C. (author), van der Schröder - Elst, J.P. (author), Ouwens, D.M. (author), Havekes, L.M. (author), Romijn, J.A. (author), Kalsbeek, A. (author), Pijl, H. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE-We recently showed that intracerebroventricular infusion of neuropeptide Y (NPY) hampers inhibition of endogenous glucose production (EGP) by insulin in mice. The down stream mechanisms responsible for these effects of NPY remain to be elucidated. Therefore, the aim of this study was to establish whether intracerebroventricular NPY...

article 2008

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Leptin deficiency per se dictates body composition and insulin action in ob/ob mice

van den Hoek, A.M. (author), Teusink, B. (author), Voshol, P.J. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), TNO Kwaliteit van Leven (author)

Obese humans are often insulin- and leptin resistant. Since leptin can affect glucose metabolism, it is conceivable that a lack of leptin signal transduction contributes to insulin resistance. It remains unclear whether leptin affects glucose metabolism via peripheral and/or central mechanistic routes. In the present study, we aimed: (i) to...

article 2008

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Moderate Alcohol Consumption and Insulin Sensitivity: Observations and Possible Mechanisms

Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)

Light to moderate alcohol consumption is associated with a reduced risk for cardiovascular diseases. Epidemiologic studies, like our analysis of the European Prospective Investigation into Cancer and Nutrition study, suggest that moderate alcohol consumption is also associated with a reduced risk of type 2 diabetes, reported for various...

article 2007

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Multivariate analysis of microarray data by principal component discriminant analysis: Prioritizing relevant transcripts linked to the degradation of different carbohydrates in Pseudomonas putida S12

van der Werf, M.J. (author), Pieterse, B. (author), van Luijk, N. (author), Schuren, F. (author), van der Werff van der - Vat, B. (author), Overkamp, K. (author), Jellema, R.H. (author), TNO Kwaliteit van Leven (author)

The value of the multivariate data analysis tools principal component analysis (PCA) and principal component discriminant analysis (PCDA) for prioritizing leads generated by microarrays was evaluated. To this end, Pseudomonas putida S12 was grown in independent triplicate fermentations on four different carbon sources, i.e. fructose, glucose,...

article 2006

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Ghrelin differentially affects hepatic and peripheral insulin sensitivity in mice

Heijboer, A.C. (author), van den Hoek, A.M. (author), Parlevliet, E.T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), Corssmit, E.P.M. (author), TNO Kwaliteit van Leven (author)

Aims/hypothesis: This study was conducted to evaluate the effects of ghrelin on insulin's capacity to suppress endogenous glucose production and promote glucose disposal in mice. To establish whether the growth hormone secretagogue (GHS) receptor can mediate the putative effect of ghrelin on the action of insulin, we also determined the...

article 2006

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Hypercholesterolemia reduces collateral artery growth more dominantly than hyperglycemia or insulin resistance in mice

van Weel, V. (author), de Vries, M. (author), Voshol, P.J. (author), Verloop, R.E. (author), Eilers, P.H.C. (author), van Hinsbergh, V.W.M. (author), van Bockel, J.H. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)

OBJECTIVE - Collateral artery development (arteriogenesis), a vital compensatory mechanism in patients with arterial obstructive disease, may be deregulated by vascular risk factors, eg, diabetes or hypercholesterolemia. Here, we compared the effects of either disturbed glucose metabolism or disturbed lipid metabolism on arteriogenesis. METHODS...

article 2006

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Response of apolipoprotein E*3-Leiden transgenic mice to dietary fatty acids: Combining liver proteomics with physiological data

de Roos, B. (author), Duivenvoorden, I. (author), Rucklidge, G. (author), Reid, M. (author), Ross, K. (author), Lamers, R.J.A.N. (author), Voshol, P.J. (author), Havekes, L.M. (author), Teusink, B. (author), TNO Kwaliteit van Leven (author)

article 2005

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Intracerebroventricular administration of melanotan II increases insulin sensitivity of glucose disposal in mice

Heijboer, A.C. (author), van den Hoek, A.M. (author), Pijl, H. (author), Voshol, P.J. (author), Havekes, L.M. (author), Romijn, J.A. (author), Corssmit, E.P.M. (author), TNO Kwaliteit van Leven (author)

Aims/hypothesis: The present study was conducted to evaluate the effects of central administration of melanotan II (MTII), a melanocortin-3/4 receptor agonist, on hepatic and whole-body insulin sensitivity, independent of food intake and body weight. Methods: Over a period of 24 h, 225 ng of MTII was injected in three aliquots into the left...

article 2005

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Endothelial function and baroreflex sensitivity according to the oral glucose tolerance test in patients with coronary artery disease and normal fasting glucose levels

Wykretowicz, A. (author), Guzik, P. (author), Bartkowiak, G. (author), Krauze, T. (author), Kasinowski, R. (author), Dziarmaga, M. (author), Wesseling, K.H. (author), Wysocki, H. (author), TNO Biomedical Instrumentation (author)

Endothelial dysfunction and reduced BRS (baroreflex sensitivity) may be present in patients with CAD (coronary artery disease). The normal fasting glucose level does not exclude abnormal glucose metabolism in patients with CAD. The aim of present study was to evaluate endothelial function and BRS according to glucose metabolism in patients with...

article 2005

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Differential effects of pharmacological liver X receptor activation on hepatic and peripheral insulin sensitivity in lean and ob/ob mice

TNO Kwaliteit van Leven (author), Grefhorst, A. (author), van Dijk, T.H. (author), Hammer, A. (author), van der Sluijs, F.H. (author), Havinga, R. (author), Havekes, L.M. (author), Romijn, J.A. (author), Groot, P.H. (author), Reijngoud, D.J. (author), Kuipers, F. (author)

Liver X receptor (LXR) agonists have been proposed to act as anti-diabetic drugs. However, pharmacological LXR activation leads to severe hepatic steatosis, a condition usually associated with insulin resistance and type 2 diabetes mellitus. To address this apparent contradiction, lean and ob/ob mice were treated with the LXR agonist GW-3965 for...

article 2005

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Sixteen hours of fasting differentially affects hepatic and muscle insulin sensitivity in mice

TNO Kwaliteit van Leven (author), Heijboer, A.C. (author), Donga, E. (author), Voshol, P.J. (author), Dang, Z.C. (author), Havekes, L.M. (author), Romijn, J.A. (author), Corssmit, E.P.M. (author)

Fasting readily induces hepatic steatosis. Hepatic steatosis is associated with hepatic insulin resistance. The purpose of the present study was to document the effects of 16 h of fasting in wild-type mice on insulin sensitivity in liver and skeletal muscle in relation to 1) tissue accumulation of triglycerides (TGs) and 2) changes in mRNA...

article 2005

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Acute inhibition of hepatic beta-oxidation in APOE*3Leiden mice does not affect hepatic VLDL secretion or insulin sensitivity

TNO Kwaliteit van Leven (author), Duivenvoorden, I. (author), Teusink, B. (author), Rensen, P.C.N. (author), Kuipers, F. (author), Romijn, J.A. (author), Havekes, L.M. (author), Voshol, P.J. (author)

Hepatic VLDL and glucose production is enhanced in type 2 diabetes and associated with hepatic steatosis. Whether the derangements in hepatic metabolism are attributable to steatosis or to the increased availability of FA metabolites is not known. We used methyl palmoxirate (MP), an inhibitor of carnitine palmitoyl transferase I, to acutely...

article 2005

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Hepatic Steatosis: A Mediator of the Metabolic Syndrome. Lessons from Animal Models

den Boer, M. (author), Voshol, P.J. (author), Kuipers, F. (author), Havekes, L.M. (author), Romijn, J.A. (author), TNO Preventie en Gezondheid (author)

Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance, and type 2 diabetes mellitus. Recently, attention has been focused on the excessive accumulation of triglycerides (TG) in the liver as part of this syndrome. In this review,...

article 2004

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A pilot study to investigate effects of inulin on Caco-2 cells through in vitro metabolic fingerprinting

Lamers, R.-J.A.N. (author), Wessels, E.C.H.H. (author), van de Sandt, J.J.M. (author), Venema, K. (author), Schaafsma, G. (author), van der Greef, J. (author), van Nesselrooij, J.H.J. (author)

Metabolic fingerprints are novel measurement tools to evaluate the biochemical status of a living organism by using 1H NMR and multivariate data analysis (MVDA). In this way, a quick evaluation of changes in health or diseased state can be made, reflected in alterations of metabolic patterns. Normally, metabolic finger-printing is based on in...

article 2003