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Kühnast, S. (author), van der Tuin, S.J.L. (author), van der Hoorn, J.W.A. (author), van Klinken, J.B. (author), Simic, B. (author), Pieterman, E. (author), Havekes, L.M. (author), Landmesser, U. (author), Lüscher, T.F. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author), Jukema, J.W. (author), Princen, H.M.G. (author)Background The residual risk that remains after statin treatment supports the addition of other LDL-C-lowering agents and has stimulated the search for secondary treatment targets. Epidemiological studies propose HDL-C as a possible candidate. Cholesteryl ester transfer protein (CETP) transfers cholesteryl esters from atheroprotective HDL to...article 2015
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van den Berg, S.A.A. (author), Heemskerk, M.M. (author), Geerling, J.J. (author), van Klinken, J.B. (author), Schaap, F.G. (author), Bijland, S. (author), Berbée, J.F.P. (author), van Harmelen, V.J.A. (author), Pronk, A.C.M. (author), Schreurs, M. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)Mutations in apolipoprotein A5 (APOA5) have been associated with hypertriglyceridemia in humans and mice. This has been attributed to a stimulating role for APOA5 in lipoprotein lipase-mediated triglyceride hydrolysis and hepatic clearance of lipoprotein remnant particles. However, because of the low APOA5 plasma abundance, we investigated an...article 2013
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Coomans, C.P. (author), van den Berg, S.A.A. (author), Houben, T. (author), van Klinken, J.B. (author), van den Berg, R. (author), Pronk, A.C.M. (author), Havekes, L.M. (author), Romijn, J.A. (author), van Dijk, K.W. (author), Biermasz, N.R. (author), Meijer, J.H. (author)Circadian rhythm disturbances are observed in, e.g., aging and neurodegenerative diseases and are associated with an increased incidence of obesity and diabetes. We subjected male C57Bl/6J mice to constant light [12-h light-light (LL) cycle] to examine the effects of a disturbed circadian rhythm on energy metabolism and insulin sensitivity. In...article 2013
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Vrins, C.L.J. (author), Out, R. (author), van Santbrink, P. (author), van der Zee, A. (author), Mahmoudi, T. (author), Groenendijk, M. (author), Havekes, L.M. (author), van Berkel, T.J.C. (author), van Dijk, K.W. (author), Biessen, E.A.L. (author)Background: The zinc finger protein Znf202 is a transcriptional suppressor of lipid related genes and has been linked to hypoalphalipoproteinemia. A functional role of Znf202 in lipid metabolism in vivo still remains to be established. Methodology and Principal Findings: We generated mouse Znf202 expression vectors, the functionality of which...article 2013
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Boon, M.R. (author), van den Berg, S.A.A. (author), Wang, Y. (author), van den Bossche, J. (author), Karkampouna, S. (author), Bauwens, M. (author), de Saint-Hubert, M. (author), van der Horst, G. (author), Vukicevic, S. (author), de Winther, M.P.J. (author), Havekes, L.M. (author), Jukema, J.W. (author), Tamsma, J.T. (author), van der Pluijm, G. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author)Background/Aims:Brown adipose tissue (BAT) dissipates energy stored in triglycerides as heat via the uncoupling protein UCP-1 and is a promising target to combat hyperlipidemia and obesity. BAT is densely innervated by the sympathetic nervous system, which increases BAT differentiation and activity upon cold exposure. Recently, Bone...article 2013
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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-1beta 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...article 2013
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Vroegrijk, I.O. (author), van Klinken, J.B. (author), van Diepen, J.A. (author), van den Berg, S.A. (author), Febbraio, M. (author), Steinbusch, L.K. (author), Glatz, J.F. (author), Havekes, L.M. (author), Voshol, P.J. (author), Rensen, P.C. (author), van Dijk, K.W. (author), van Harmelen, V. (author)Objective: The scavenger receptor CD36 facilitates the cellular uptake of long-chain fatty acids. As CD36-deficiency attenuates the development of high fat diet (HFD)-induced obesity, the role of CD36-deficiency in preadipocyte recruitment and adipocyte function was set out to characterize. Design and methods: Fat cell size and number were...article 2013
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Louwe, M.C. (author), van der Hoorn, J.W.A. (author), van den Berg, S.A.A. (author), Wouter Jukema, J. (author), Romijn, J.A. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author), Smit, J.W.A. (author), Steendijk, P. (author)Increased availability of fatty acids released from insulin-resistant adipose tissue may lead to excess fatty acid uptake in nonadipose organs, including the heart. Accumulation of toxic fatty acid intermediates may affect cardiac function. Our aim was to identify to which extent high-fat diet feeding leads to alterations in cardiac function and...article 2012
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Vroegrijk, I.O.C.M. (author), van Diepen, J.A. (author), van den Berg, S.A. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Darland, G. (author), Konda, V. (author), Tripp, M.L. (author), Bland, J.S. (author), Voshol, P.J. (author)Objective: We investigated whether a reduced iso-α acid derived from an extract of Humulus lupulus L., META060, had an effect on weight gain, body composition, and metabolism in a high-fat–diet (HFD) fed mouse model. Methods: Weight gain was monitored for up to 20 wk in mice receiving a low-fat diet, an HFD, or an HFD supplemented with META060...article 2012
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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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de Vogel-van den Bosch, J. (author), van den Berg, S.A.A. (author), Bijland, S. (author), Voshol, P.J. (author), Havekes, L.M. (author), Romijn, H.A. (author), Hoeks, J. (author), van Beurden, D. (author), Hesselink, M.K.C. (author), Schrauwen, P. (author), van Dijk, K.W. (author)Excess dietary long-chain fatty acid (LCFA) intake results in ectopic lipid accumulation and insulin resistance. Since medium-chain fatty acids (MCFA) are preferentially oxidized over LCFA, we hypothesized that diets rich in MCFA result in a lower ectopic lipid accumulation and insulin resistance compared to diets rich in LCFA. Feeding mice high...article 2011
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Alkemade, F.E. (author), van Vliet, P. (author), Henneman, P. (author), van Dijk, K.W. (author), Hierck, B.P. (author), van Munsteren, J.C. (author), Scheerman, J.A. (author), Goeman, J.J. (author), Havekes, L.M. (author), Gittenberger-de Groot, A.C. (author), van den Elsen, P.J. (author), de Ruiter, M.C. (author), TNO Kwaliteit van Leven (author)We recently demonstrated that neointima formation of adult heterozygous apolipoprotein E (apoE+/-) offspring from hypercholesterolemic apoE-/- mothers was significantly increased as compared with genetically identical apoE+/- offspring from normocholesterolemic wild-type mothers. Since atherosclerosis is the consequence of a complex...article 2010
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van den Berg, S.A.A. (author), Nabben, M. (author), Bijland, S. (author), Voshol, P.J. (author), van Klinken, J.B. (author), Havekes, L.M. (author), Romijn, J.A. (author), Hoeks, J. (author), Hesselink, M.K. (author), Schrauwen, P. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)Considerable variation in energy expenditure is observed in C57Bl/6 mice on a high-fat diet. Because muscle tissue is a major determinant of whole-body energy expenditure, we set out to determine the variation in energy expenditure and its possible association with skeletal muscle mitochondrial function upon high-fat diet intervention. Metabolic...article 2010
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TNO Kwaliteit van Leven (author), Bijland, S. (author), van den Berg, S.A.A. (author), Voshol, P.J. (author), van den Hoek, A.M. (author), Princen, H.M.G. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author)The cholesteryl ester transfer protein (CETP) facilitates the bidirectional transfer of cholesteryl esters and triglycerides (TG) between HDL and (V)LDL. By shifting cholesterol in plasma from HDL to (V)LDL in exchange for VLDL-TG, CETP aggravates atherosclerosis in hyperlipidemic APOE*3-Leiden (E3L) mice. The aim of this study was to...article 2010
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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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Voshol, P.J. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author), Romijn, J.A. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)The obesity epidemic is associated with an increased incidence of type 2 diabetes, cardiovascular morbidity and various types of cancer. A better insight into the molecular mechanisms that underlie adipogenesis and obesity may result in novel therapeutic handles to fight obesity and these associated diseases. Adipogenesis is determined by the...article 2009
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Henneman, P. (author), van der Sman-de Beer, F. (author), Moghaddam, P.H. (author), Huijts, P. (author), Stalenhoef, A.F.H. (author), Kastelein, J.J.P. (author), van Duijn, C.M. (author), Havekes, L.M. (author), Frants, R.R. (author), van Dijk, K.W. (author), Smelt, A.H.M. (author), TNO Kwaliteit van Leven (author)Type III hyperlipoproteinemia (HLP) is mainly found in homozygous apolipoprotein (APO) E2 (R158C) carriers. Genetic factors contributing to the expression of type III HLP were investigated in 113 hyper- and 52 normolipidemic E2/2 subjects, by testing for polymorphisms in APOC3, APOA5, HL (hepatic lipase) and LPL (lipoprotein lipase) genes. In...article 2009
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TNO Kwaliteit van Leven (author), Thissen, U. (author), Wopereis, S. (author), van den Berg, S.A.A. (author), Bobeldijk, I. (author), Kleemann, R. (author), Kooistra, T. (author), van Dijk, K.W. (author), van Ommen, B. (author), Smilde, A.K. (author)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...article 2009
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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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de Ruiter, M.C. (author), Alkemade, F.E. (author), de Gittenberger - Groot, A.C. (author), Poelmann, R.E. (author), Havekes, L.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)In this review, we briefly summarize the possible signals crossing the placental barrier and discuss the molecular mechanisms of epigenetic programming in the developing fetus leading to increased athero-susceptibility of the vessel wall. © 2008 Wolters Kluwer Health | Lippincott Williams & Wilkins.article 2008