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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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Abe, N. (author), Kato, S. (author), Tsuchida, T. (author), Sugimoto, K. (author), Saito, R. (author), Verschuren, L. (author), Kleemann, R. (author), Oka, K. (author)Non-alcoholic steatohepatitis (NASH) is a fast-growing liver disease in the Western world. Currently, only a few animal models show both the metabolic and histological features of human NASH. We aimed to explore murine NASH models in a time dependent manner that exhibit metabolic, histological and transcriptomic hallmarks of human NASH. For this...article 2019
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Remels, A.H.V. (author), Derks, W.J.A. (author), Cillero-Pastor, B. (author), Verhees, K.J.P. (author), Kelders, M.C. (author), Heggermont, W. (author), Carai, P. (author), Summer, G. (author), Ellis, S.R. (author), de Theije, C.C. (author), Heeren, R.M.A. (author), Heymans, S. (author), Papageorgiou, A.P. (author), van Bilsen, M. (author)Acute viral myocarditis (VM), characterised by leukocyte infiltration and dysfunction of the heart, is an important cause of sudden cardiac death in young adults. Unfortunately, to date, the pathological mechanisms underlying cardiac failure in VM remain incompletely understood. In the current study, we investigated if acute VM leads to cardiac...article 2018
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Wambaugh, J.F. (author), Hughes, M.F. (author), Ring, C.L. (author), MacMillan, D.K. (author), Ford, J. (author), Fennell, T.R. (author), Black, S.R. (author), Snyder, R.W. (author), Sipes, N.S. (author), Wetmore, B.A. (author), Westerhout, J. (author), Setzer, R.W. (author), Pearce, R.G. (author), Simmons, J.E. (author), Thomas, R.S. (author)Prioritizing the risk posed by thousands of chemicals potentially present in the environment requires exposure, toxicity, and toxicokinetic (TK) data, which are often unavailable. Relatively high throughput, in vitro TK (HTTK) assays and in vitro-to-in vivo extrapolation (IVIVE) methods have been developed to predict TK, but most of the in vivo...article 2018
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Activity based protein profiling leads to identification of novel protein targets for nerve agent VXCarmany, D. (author), Walz, A.J. (author), Hsu, F.L. (author), Benton, B. (author), Burnett, D. (author), Gibbons, J. (author), Noort, D. (author), Glaros, T. (author), Sekowski, J.W. (author)Organophosphorus (OP) nerve agents continue to be a threat at home and abroad during the war against terrorism. Human exposure to nerve agents such as VX results in a cascade of toxic effects relative to the exposure level including ocular miosis, excessive secretions, convulsions, seizures, and death. The primary mechanism behind these overt...article 2017
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van de Steeg, E. (author), Läppchen, T. (author), Aguilera, B. (author), Jansen, H.T. (author), Muilwijk, D. (author), Vermue, R. (author), van der Hoorn, J.W. (author), Donato, K. (author), Rossin, R. (author), de Visser, P.C. (author), Vlaming, M.L.H. (author)Antisense oligonucleotides (AONs) are promising candidates for treatment of Duchenne muscular dystrophy (DMD), a severe and progressive disease resulting in premature death. However, more knowledge on the pharmacokinetics of new AON drug candidates is desired for effective application in the clinic. We assessed the feasibility of using...article 2017
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Hoeke, G. (author), Wang, Y. (author), van Dam, A.D. (author), Mol, M. (author), Gart, E. (author), Klop, H.G. (author), van den Berg, S.M. (author), Pieterman, E.H. (author), Princen, H.M.G. (author), Groen, A.K. (author), Rensen, P.C.N. (author), Berbée, J.F.P. (author), Boon, M.R. (author)Background and aims Activation of brown adipose tissue (BAT) reduces both hyperlipidemia and atherosclerosis by increasing the uptake of triglyceride-derived fatty acids by BAT, accompanied by formation and clearance of lipoprotein remnants. We tested the hypothesis that the hepatic uptake of lipoprotein remnants generated by BAT activation...article 2017
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Raaphorst, R.M. (author), Savolainen, H. (author), Cantore, M. (author), van de Steeg, E. (author), van Waarde, A. (author), Colabufo, N.A. (author), Elsinga, P.H. (author), Lammertsma, A.A. (author), Windhorst, A.D. (author), Luurtsema, G. (author)Positron emission tomography (PET) imaging of P-glycoprotein (P-gp) in the blood-brain barrier can be important in neurological diseases where P-gp is affected, such as Alzheimer’s disease. Radiotracers used in the imaging studies are present at very small, nanomolar, concentration, whereas in vitro assays where these tracers are characterized,...article 2017
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Schoemaker, M.H. (author), Kleemann, R. (author), Morrison, M.C. (author), Verheij, J. (author), Salic, K. (author), van Tol, E.A.F. (author), Kooistra, T. (author), Wielinga, P.Y. (author)Background: Obesity frequently associates with the development of non-alcoholic fatty liver disease (NAFLD) and atherosclerosis. Chronic inflammation in white adipose tissue (WAT) seems to be an important driver of these manifestations. Objective: This study investigated a combination of an extensively hydrolyzed casein (eHC), docosahexaenoic...article 2017
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Bolle, L.J. (author), de Jong, C.A.F. (author), Bierman, S.M. (author), van van Beek, P.J.G. (author), Wessels, P.W. (author), Blom, E. (author), van Damme, C.J.G. (author), Winter, H.V. (author), Dekeling, R.P.A. (author)Concern exists about the potential effects of pile-driving sounds on fish, but evidence is limited, especially for fish larvae. A device was developed to expose larvae to accurately reproduced pile-driving sounds. Controlled exposure experiments were carried out to examine the lethal effects in common sole larvae. No significant effects were...conference paper 2016
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Cnubben, N.H.P. (author), Tel, S.L. (author), Hemmes, M.A. (author), Langenkamp-Brand, A. (author), Grossouw, D. (author), Jansen, H.T. (author), de Bie, B.T.H.J. (author)Background: Worldwide obesity has nearly doubled since 1980 and is a leading risk for global deaths, profoundly affecting morbidity, mortality, health-care costs, and professional and personal quality of life. Treatment of obesity and its consequences include lifestyle intervention, pharmacotherapy, and bariatric surgery. Polyglucosamines have...article 2016
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van der Heijden, R.A. (author), Morrison, M.C. (author), Sheedfar, F. (author), Mulder, P. (author), Schreurs, M. (author), Hommelberg, P.P.H. (author), Hofker, M.H. (author), Schalkwijk, C. (author), Kleemann, R. (author), Tietge, U.J.F. (author), Koonen, D.P.Y. (author), Heeringa, P. (author)Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential....article 2016
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Ripken, D. (author), van der Wielen, N. (author), van der Meulen, J. (author), Schuurman, T. (author), Witkamp, R.F. (author), Hendriks, H.F.J. (author), Koopmans, S.J. (author)The vagal nerve and gut hormones CCK and GLP-1 play important roles in the control of food intake. However, it is not clear to what extent CCK and GLP-1 increase satiation by stimulating receptors located on abdominal vagal nerve endings or via receptors located elsewhere. This study aimed to further explore the relative contribution of the...article 2015
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Liang, W. (author), Verschuren, L. (author), Mulder, P. (author), van der Hoorn, J.W.A. (author), Verheij, J. (author), van Dam, A.D. (author), Boon, M.R. (author), Princen, H.M.G. (author), Havekes, L.M. (author), Kleemann, R. (author), van den Hoek, A.M. (author)BACKGROUND AND PURPOSE: Salsalate (salicylsalicylic acid) is an anti-inflammatory drug that was recently found to exert beneficial metabolic effects on glucose and lipid metabolism. Although its utility in the prevention and management of a wide range of vascular disorders, including type 2 diabetes and metabolic syndrome has been suggested...article 2015
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Walczak, A.P. (author), Hendriksen, P.J.M. (author), Woutersen, R.A. (author), van der Zande, M. (author), Undas, A.K. (author), Helsdingen, R. (author), van den Berg, H.H.J. (author), Rietjens, I.M.C.M. (author), Bouwmeester, H. (author)The likelihood of oral exposure to nanoparticles (NPs) is increasing, and it is necessary to evaluate the oral bioavailability of NPs. In vitro approaches could help reducing animal studies, but validation against in vivo studies is essential. Previously, we assessed the translocation of 50 nm polystyrene NPs of different charges (neutral,...article 2015
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Mesens, N. (author), Crawfordb, A.D. (author), Menke, A. (author), Hung, P.D. (author), van Goethem, F. (author), Nuyts, R. (author), Hansen, E. (author), Wolterbeek, A. (author), van Gompel, J. (author), de Witte, P. (author), Esguerra, C.V. (author)Drug-induced liver injury (DILI) is poorly predicted by single-cell-based assays, probably because of the lack of physiological interactions with other cells within the liver. An intact whole liver system such as one present in zebrafish larvae could provide added value in a screening strategy for DILI; however, the possible occurrence of other...article 2015
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Berbeé, J.F.P. (author), Boon, M.R. (author), Khedoe, P.P.S.J. (author), Bartelt, A. (author), Schlein, C. (author), Worthmann, A. (author), Kooijman, S. (author), Hoeke, G. (author), Mol, I.M. (author), John, C. (author), Jung, C. (author), Vazirpanah, N. (author), Brouwers, L.P.J. (author), Gordts, P.L.S.M. (author), Esko, J.D. (author), Hiemstra, P.S. (author), Havekes, L.M. (author), Scheja, L. (author), Heeren, J. (author), Rensen, P.C.N. (author)Brown adipose tissue (BAT) combusts high amounts of fatty acids, thereby lowering plasma triglyceride levels and reducing obesity. However, the precise role of BAT in plasma cholesterol metabolism and atherosclerosis development remains unclear. Here we show that BAT activation by b3-adrenergic receptor stimulation protects from atherosclerosis...article 2015
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Bodin, J. (author), Kocbach Bølling, A. (author), Wendt, A. (author), Eliasson, L. (author), Becher, R. (author), Kuper, F. (author), Løvik, M. (author), Nygaard, U.C. (author)Type 1 diabetes mellitus (T1DM) is an autoimmune destruction of insulin producing pancreatic beta-cells due to a genetic predisposition and can be triggered by environmental factors. We have previously shown that bisphenol A (BPA) accelerates the spontaneous development of diabetes in non-obese diabetic (NOD) mice. Here, we hypothesized that...article 2015
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Derous, D. (author), Kelder, T. (author), van Schothorst, E.M. (author), van Erk, M. (author), Voigt, A. (author), Klaus, S. (author), Keijer, J. (author), Radonjic, M. (author)Health is influenced by interplay of molecular, physiological and environmental factors. To effectively maintain health and prevent disease, health-relevant relations need to be understood at multiple levels of biological complexity. Network-based methods provide a powerful platform for integration and mining of data and knowledge characterizing...article 2015
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Mulder, P. (author), Stavro, P.M. (author), Manuel Suárez, M. (author), Arola-Arnal, A. (author), van Duyvenvoorde, W. (author), Kooistra, T. (author), Wielinga, P.Y. (author), Kleemann, R. (author)Background and Aims As dietary saturated fatty acids are associated with metabolic and cardiovascular disease, a potentially interesting strategy to reduce disease risk is modification of the quality of fat consumed. Vegetable oils represent an attractive target for intervention, as they largely determine the intake of dietary fats. Furthermore,...article 2015