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Gart, E. (author), Souto Lima, E. (author), Schuren, F. (author), de Ruiter, C.G.F. (author), Attema, J. (author), Verschuren, L. (author), Keijer, J. (author), Salic, K. (author), Morrison, M.C. (author), Kleemann, R. (author)
Development of non-alcoholic fatty liver disease (NAFLD) is linked to obesity, adipose tissue inflammation, and gut dysfunction, all of which depend on diet. So far, studies have mainly focused on diet-related fecal microbiota changes, but other compartments may be more informative on host health. We present a first systematic analysis of...
article 2019
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Hoevenaars, F.P.M. (author), Esser, D. (author), Schutte, S. (author), Priebe, M.G. (author), Vonk, R.J. (author), van den Brink, W.J. (author), van der Kamp, J.W. (author), Stroeve, J.H.M. (author), Afman, L.A. (author), Wopereis, S. (author)
Background. Whole grain wheat (WGW) consumption is associated with health benefits in observational studies. However, WGW randomized controlled trial (RCT) studies show mixed effects. Objectives. The health impact of WGW consumption was investigated by quantification of the body's resilience, which was defined as the “ability to adapt to a...
article 2019
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Morrison, M.C. (author), Kleemann, R. (author), van Koppen, A. (author), Hanemaaijer, R. (author), Verschuren, L. (author)
Introduction: It is generally accepted that metabolic inflammation in the liver is an important driver of disease progression in NASH and associated matrix remodeling/fibrosis. However, the exact molecular inflammatory mechanisms are poorly defined in human studies. Investigation of key pathogenic mechanisms requires the use of pre-clinical...
article 2018
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van Groen, B.D. (author), van de Steeg, E. (author), Mooij, M.G. (author), van Lipzig, M.M.H. (author), de Koning, B.A.E. (author), Verdijk, R.M. (author), Wortelboer, H.M. (author), Gaedigk, R. (author), Bi, C. (author), Leeder, S. (author), van Schaik, R.H.N. (author), van Rosmalen, J. (author), Tibboel, D. (author), Vaes, W.H. (author), de Wildt, S.N. (author)
Background Hepatic membrane transporters are involved in the transport of many endogenous and exogenous compounds, including drugs. We aimed to study the relation of age with absolute transporter protein expression in a cohort of 62 mainly fetus and newborn samples. Methods Protein expressions of BCRP, BSEP, GLUT1, MCT1, MDR1, MRP1, MRP2, MRP3,...
article 2018
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van der Heijden, R.A. (author), Fareeba Sheedfar, F. (author), Morrison, M.C. (author), Hommelberg, P.P.H. (author), Kor1, D. (author), Kloosterhuis, N.J. (author), Gruben, N. (author), Youssef, S.A. (author), de Bruin, A. (author), Hofker, M.H. (author), Kleemann, R. (author), Koonen, D.P.Y. (author), Heeringa1, P. (author)
Metabolic inflammation in adipose tissue and the liver is frequently observed as a result of diet-induced obesity in human and rodent studies. Although the adipose tissue and the liver are both prone to become chronically inflamed with prolonged obesity, their individual contribution to the development of metabolic inflammation remains...
article 2015
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van der Tuin, S.J. (author), Kühnast, S. (author), Berbée, J. (author), Verschuren, L. (author), Pieterman, E.J. (author), Havekes, L.M. (author), van der Hoorn, J.W. (author), Rensen, P.C. (author), Jukema, J.W. (author), Princen, H.M. (author), Willems van Dijk, K. (author), Wang, Y. (author)
Recently, we showed in APOE*3-Leiden.CETP mice that anacetrapib attenuated atherosclerosis development by reducing (V)LDL-C rather than by raising HDL-C. Here, we investigated the mechanism by which anacetrapib reduces (V)LDL-C and whether this effect was dependent on the inhibition of CETP. APOE*3-Leiden.CETP mice were fed a Western type diet...
article 2015
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Geerling, J.J. (author), Boon, M.R. (author), Kooijman, S. (author), Parlevliet, E.T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Meurs, I.M. (author), Rensen, P.C.N. (author)
Abstract Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points to a...
article 2014
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Bosgra, S. (author), van de Steeg, E. (author), Vlaming, M.L. (author), Verhoeckx, K.C. (author), Huisman, M.T. (author), Verwei, M. (author), Wortelboer, H.M. (author)
In contrast to primary hepatocytes, estimating carrier-mediated hepatic disposition by using a panel of single transfected cell-lines provides direct information on the contribution of the individual transporters to the net disposition. The most direct way to correct for differences in transporter abundance between cell-lines and tissue is by...
article 2014
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Kooijman, S. (author), Boon, M.R. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van de Pol, V. (author), Romijn, J.A. (author), Havekes, L.M. (author), Meurs, I. (author), Rensen, P.C.N. (author)
The melanocortin system is an important regulator of energy balance, and melanocortin 4 receptor (MC4R) deficiency is the most common monogenic cause of obesity. We investigated whether the relationship between melanocortin system activity and energy expenditure (EE) is mediated by brown adipose tissue (BAT) activity. Therefore, female APOE∗3...
article 2014
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van Diepen, J.A. (author), Stienstra, R. (author), Vroegrijk, I.O.C.M. (author), van den Berg, S.A.A. (author), Salvatori, D. (author), Hooiveld, G.J. (author), Kersten, S. (author), Tack, C.J. (author), Netea, M.G. (author), Smit, J.W.A. (author), Joosten, L.A.B. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)
Caspase-1 is known to activate the proinflammatory cytokines IL-1β and IL-18. Additionally, it can cleave other substrates, including proteins involved in metabolism. Recently, we showed that caspase-1 deficiency in mice strongly reduces high-fat diet-induced weight gain, at least partly caused by an increased energy production. Increased feces...
article 2013
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Li, Z. (author), Wang, Y. (author), van der Sluis, R.J. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), van Eck, M. (author), van Berkel, T.J.C. (author), Rensen, P.C.N. (author), Hoekstra, M. (author)
The anti-dyslipidemic drug niacin has recently been shown to reduce the hepatic expression and plasma levels of CETP. Since liver macrophages contribute to hepatic CETP expression, we investigated the role of macrophages in the CETP-lowering effect of niacin in mice. In vitro studies showed that niacin does not directly attenuate CETP expression...
article 2012
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Wong, M.C. (author), van Diepen, J.A. (author), Hu, L. (author), Guigas, B. (author), de Boer, H.C. (author), van Puijvelde, G.H. (author), Kuiper, J. (author), van Zonneveld, A.J. (author), Shoelson, S.E. (author), Voshol, P.J. (author), Romijn, J.A. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Rensen, P.C.N. (author), Hiemstra, P.S. (author), Berbée, J.F.P. (author)
Objective: The liver is the key organ involved in systemic inflammation, but the relation between hepatic inflammation and atherogenesis is poorly understood. Since nuclear factor-κB (NF-κB) is a central regulator of inflammatory processes, we hypothesized that chronically enhanced hepatic NF-κB activation, through hepatocyte-specific expression...
article 2012
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Lu, Y. (author), Boekschoten, M.V. (author), Wopereis, S. (author), Müller, M. (author), Kersten, S. (author)
Comparative transcriptomic and metabolomic analysis of fenofibrate and fish oil treatments in mice. Physiol Genomics 43: 1307-1318, 2011. First published September 27, 2011; doi:10.1152/physiolgenomics.00100.2011. Elevated circulating triglycerides, which are considered a risk factor for cardiovascular disease, can be targeted by treatment with...
article 2011
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Diepen, J.A.V. (author), Wong, M.C. (author), Guigas, B. (author), Bos, J. (author), Stienstra, R. (author), Hodson, L. (author), Shoelson, S.E. (author), Berbée, Jimmy F.P. (author), Rensen, P.C.N. (author), Romijn, J.A. (author), Havekes, L.M. (author), Voshol, P.J. (author), TNO Kwaliteit van Leven (author)
Low-grade inflammation in different tissues, including activation of the nuclear factor k B pathway in liver, is involved in metabolic disorders such as type 2 diabetes and cardiovascular diseases (CVDs). In this study, we investigated the relation between chronic hepatocyte-specifi c overexpression of IkB kinase (IKK)- β and...
article 2011
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van Ginneken, V.J.T. (author), Verheij, E. (author), Hekman, M. (author), van der Greef, J. (author), Feskens, E.J.M. (author), Poelmann, R.E. (author)
We investigated with LC-MS techniques, measuring approximately 109 lipid compounds, in mouse brain and liver tissue after 48 hours of starvation and a High-Fat Diet if brain and liver lipid composition changed. We measured Cholesterolesters (ChE), Lysophosphatidyl-cholines (LPC), Phosphatidylcholine (PC), Sphingomyelin (SPM) and Triacylglycerols...
bookPart 2011
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Wielinga, P.Y. (author), Yakala, G.K. (author), Heeringa, P. (author), Kleemann, R. (author), Kooistra, T. (author)
Background: Alternate day calorie restriction (CR) has been shown to be almost as beneficial as daily CR. The question arises whether this concept is also applicable to alternating dietary composition. Objective: To seek evidence that alternating high cholesterol (HC) - cholesterol-free (CON) Western diet can effectively diminish hepatic and...
article 2011
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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), TNO Kwaliteit van Leven (author)
The peroxisome proliferator-activated receptor alpha (PPARα) 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 controversial,...
article 2010
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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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de Haan, W. (author), de Vries-van der Weij, J. (author), Mol, I.M. (author), Hoekstra, M. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Pregnane X receptor (PXR) agonism has been shown to affect multiple steps in both the synthesis and catabolism of HDL, but its integrated effect on HDL metabolism in vivo remains unclear. The aim of this study was to evaluate the net effect of PXR agonism on HDL metabolism in ApoE*3-Leiden (E3L) and E3L.CETP mice, well-established models for...
article 2009
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Parlevliet, E.T. (author), Schröder-van der Elst, J.P. (author), Corssmit, E.P.M. (author), Picha, K. (author), O'Neil, K. (author), Stojanovic-Susulic, V. (author), Ort, T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Pijl, H. (author), TNO Kwaliteit van Leven (author)
CNTO736 is a glucagon-like peptide (GLP) 1 receptor agonist that incorporates a GLP-1 peptide analog linked to the Mimeti-body platform. We evaluate the potential of acute and chronic CNTO736 treatment on insulin sensitivity and very low-density lipoprotein (VLDL) metabolism. For acute studies, diet-induced insulin-resistant C57BL76 mice...
article 2009
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