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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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Guigas, B. (author), de Leeuw van Weenen, J.E. (author), van Leeuwen, N. (author), Simonis-Bik, A.M. (author), van Haeften, T.W. (author), Nijpels, G. (author), Houwing-Duistermaat, J.J. (author), Beekman, M. (author), Deelen, J. (author), Havekes, L.M. (author), Penninx, B.W.J.H. (author), Vogelzangs, N. (author), van 't Riet, E. (author), Dehghan, A. (author), Hofman, A. (author), Witteman, J.C. (author), Uitterlinden, A.G. (author), Grarup, N. (author), Jørgensen, T. (author), Witte, D.R. (author), Lauritzen, T. (author), Hansen, T. (author), Pedersen, O. (author), Hottenga, J. (author), Romijn, J.A. (author), Diamant, M. (author), Kramer, M.H.H. (author), Heine, R.J. (author), Willemsen, G. (author), Dekker, J.M. (author), Eekhoff, E.M. (author), Pijl, H. (author), de Geus, E.J. (author), Slagboom, P.E. (author), 't Hart, L.M. (author)
Aims: Modulation of dopamine receptor D2 (DRD2) activity affects insulin secretion in both rodents and isolated pancreatic β-cells. We hypothesized that single nucleotide polymorphisms in the DRD2/ANKK1 locus may affect susceptibility to Type 2 diabetes in humans. Methods: Four potentially functional variants in the coding region of the DRD2...
article 2014
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Liang, W. (author), Menke, A.L. (author), Driessen, A. (author), Koek, G.H. (author), Lindeman, J.H. (author), Stoop, R. (author), Havekes, L.M. (author), Kleemann, R. (author), van den Hoek, A.M. (author)
Results: The criteria macrovesicular steatosis, microvesicular steatosis, hepatocellular hypertrophy, inflammation and fibrosis were generally applicable to rodent NAFLD. The inter-observer reproducibility (evaluated using the Intraclass Correlation Coefficient) between the ten observers was high for the analysis of macrovesicular steatosis and...
article 2014
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Boon, M.R. (author), Kooijman, S. (author), van Dam, A.D. (author), Pelgrom, L.R. (author), Berbée, J.F.P. (author), Visseren, C.A.R. (author), van Aggele, R.C. (author), van den Hoek, A.M. (author), Sips, H.C.M. (author), Lombès, M. (author), Havekes, L.M. (author), Tamsma, J.T. (author), Guigas, B. (author), Meijer, O.C. (author), Jukema, J.W. (author), Rensen, P.C.N. (author)
The endocannabinoid system is an important player in energy metabolism by regulating appetite, lipolysis, and energy expenditure. Chronic blockade of the cannabinoid 1 receptor (CB1R) leads to long-term maintenance of weight loss and reduction of dyslipidemia in experimental and human obesity. The molecular mechanism by which CB1R blockade...
article 2014
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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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de Leeuw van Weenen, J.E. (author), Parlevliet, E.T. (author), Maechler, P. (author), Havekes, L.M. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Pijl, H. (author), Guigas, B. (author), TNO Kwaliteit van Leven (author)
Treatment with the dopamine receptor D2 (DRD2) agonist bromocriptine improves metabolic features in obese patients with type 2 diabetes by a still unknown mechanism. In the present study, we investigated the acute effect of bromocriptine and its underlying mechanism(s) on insulin secretion both in vivo and in vitro. For this purpose, C57Bl6/J...
article 2010
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Berbée, J.F.P. (author), Mooijaart, S.P. (author), de Craen, A.J.M. (author), Havekes, L.M. (author), van Heemst, D. (author), Rensen, P.C.N. (author), Westendorp, R.G.J. (author), TNO Kwaliteit van Leven (author)
The high-density lipoprotein (HDL) constituent apolipoprotein CI (apoCI) protects mice against mortality in bacterial sepsis. We assessed whether high plasma apoCI levels protect against mortality from infection in humans. We determined plasma levels of apoCI, lipids, and C-reactive protein in 85-year-old participants of the prospective...
article 2008
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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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Hu, L. (author), van der Hoogt, C.C. (author), Espirito Santo, S.M.S. (author), Out, R. (author), Kypreos, K.E. (author), van Vlijmen, B.J.M. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
LPL activity plays an important role in preceding the VLDL remnant clearance via the three major apolipoprotein E (apoE)-recognizing receptors: the LDL receptor (LDLr), LDL receptor-related protein (LRP), and VLDL receptor (VLDLr). The aim of this study was to determine whether LPL activity is also important for VLDL remnant clearance...
article 2008
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de Haan, W. (author), van der Hoogt, C.C. (author), Westerterp, M. (author), Hoekstra, M. (author), Dallinga-Thie, G.M. (author), Princen, H.M.G. (author), Romijn, J.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Objective: In addition to lowering low-density lipoprotein (LDL)-cholesterol, statins modestly increase high-density lipoprotein (HDL)-cholesterol in humans and decrease cholesteryl ester transfer protein (CETP) mass and activity. Our aim was to determine whether the increase in HDL depends on CETP expression. Methods and results: APOE*3-Leiden ...
article 2008
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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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Schippers, E.F. (author), Berbée, J.F.P. (author), van Disseldorp, I.M. (author), Versteegh, M.I.M. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dissel, J.T. (author), TNO Kwaliteit van Leven (author)
Objective: Experimental models show that apolipoprotein CI (apoCI) binds and enhances the inflammatory response to endotoxin. We studied in patients undergoing cardiopulmonary bypass surgery (CPB) and experiencing endotoxemia during reperfusion whether plasma apoCI levels correlate with the inflammatory response and perioperative cytokine...
article 2008
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Berbée, J.F.P. (author), van der Hoogt, C.C. (author), de Haas, C.J.C. (author), van Kessel, K.P.M. (author), Dallinga-Thie, G.M. (author), Romijn, J.A. (author), Havekes, L.M. (author), van Leeuwen, H.J. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Objective: We recently reported that apolipoprotein CI (apoCI) protects against the development of murine bacterial sepsis. We now examined the time course of plasma apoCI levels in survivors and non-survivors of severe sepsis. Design: Prospective study in patients meeting predefined criteria for severe sepsis. Setting: University hospital...
article 2008
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Gerritsen, G. (author), van der Hoogt, C.C. (author), Schaap, F.G. (author), Voshol, P.J. (author), Kypreos, K.E. (author), Maeda, N. (author), Groen, A.K. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)
Apolipoprotein E2 (apoE2)-associated hyperlipidemia is characterized by a disturbed clearance of apoE2-enriched VLDL remnants. Because excess apoE2 inhibits LPL-mediated triglyceride (TG) hydrolysis in vitro, we in vestigated whether direct or indirect stimulation of LPL activity in vivo reduces the apoE2-associated hypertriglyc-eridemia. Here,...
article 2008
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Nagelkerken, L. (author), Verzaal, P. (author), Lagerweij, T. (author), Persoon-Deen, C. (author), Berbee, J.F.P. (author), Prens, E.P. (author), Havekes, L.M. (author), Oranje, A.P. (author), TNO Kwaliteit van Leven (author)
Mice with transgenic expression of human apolipoprotein C1 (APOC1) in liver and skin have strongly increased serum levels of cholesterol, triglycerides, and free fatty acids, indicative of a disturbed lipid metabolism. Importantly, these mice display a disturbed skin barrier function, evident from increased transepidermal water loss, and...
article 2008
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Krom, Y.D. (author), Pires, N.M.M. (author), Jukema, J.W. (author), de Vries, M.R. (author), Frants, R.R. (author), Havekes, L.M. (author), van Dijk, K.W. (author), Quax, P.H.A. (author), TNO Kwaliteit van Leven (author)
Objective: Neointima formation is the underlying mechanism of (in-stent) restenosis. 17β-Estradiol (E2) is known to inhibit injury-induced neointima formation and post-angioplasty restenosis. Estrogen receptor alpha (ERα) has been demonstrated to mediate E2 anti-restenotic properties. However, the role of estrogen receptor beta (ERβ) is not...
article 2007
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van Ginneken, V. (author), Verhey, E. (author), Poelmann, R. (author), Ramakers, R. (author), van Dijk, K.W. (author), Ham, L. (author), Voshol, P. (author), Havekes, L. (author), van Eck, M. (author), van der Greef, J. (author), TNO Kwaliteit van Leven (author)
A metabolomic approach was applied to a mouse model of starvation-induced hepatic steatosis. After 24 h of fasting it appears that starvation reduced the phospholipids (PL), free cholesterol (FC), and cholesterol esters (CE) content of low-density lipoproteins (LDL). In liver lipid profiles major changes were observed using different techniques....
article 2007
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Westerterp, M. (author), Berbée, J.F.P. (author), Delsing, D.J.M. (author), Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), Offerman, E.H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Mice that overexpress human apolipoprotein C-I (apoC-I) homozygously (APOC1+/+ mice) are protected against obesity and show cutaneous abnormalities. Although these effects can result from our previous observation that apoC-I inhibits FFA generation by LPL, we have also found that apoC-I impairs the uptake of a FFA analog in adipose tissue. In...
article 2007
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Henneman, P. (author), Schaap, F.G. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Frants, R.R. (author), van Tol, A. (author), Hattori, H. (author), Smelt, A.H.M. (author), van Dijk, K.W. (author), TNO Kwaliteit van Leven (author)
Objective: The recently discovered apoAV is hypothesized to affect triglyceride metabolism by stimulating the lipolysis of triglycerides in VLDL and chylomicrons. We set out to determine the association between increased serum TG levels, plasma apoAV levels, and polymorphism of the APOA5 gene, with specific emphasis on the APOA5 S19W variation....
article 2007
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Westerterp, M. (author), van Eck, M. (author), de Haan, W. (author), Offerman, E.H. (author), van Berkel, T.J.C. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Objective: Apolipoprotein CI (apoCI) is expressed in the liver and in macrophages, and has several roles in lipid metabolism. Since macrophage apoCI expression might affect macrophage lipid homeostasis and atherosclerotic lesion development locally in the arterial wall, we investigated the effect of both systemic and macrophage apoCI on...
article 2007
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