Searched for: subject:"Animals"
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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 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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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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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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Kaman, W.E. (author), Wolterink, A.F.W.M. (author), Bader, M. (author), Boele, L.C.L. (author), van der Kleij, D. (author), TNO Defensie en Veiligheid (author)
The endogenous danger signal bradykinin was recently found implicated in the development of immunity against parasites via dendritic cells. We here report an essential role of the B2 (B2R) bradykinin receptor in the early immune response against Listeria infection. Mice deficient in B2R (B2R-/- mice) were shown to suffer from increased hepatic...
article 2009
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Bobeldijk, I. (author), Hekman, M. (author), van der Vries de- Weij, J. (author), Coulier, L. (author), Ramaker, R. (author), Kleemann, R. (author), Kooistra, T. (author), Rubingh, C. (author), Freidig, A. (author), Verheij, E. (author), TNO Kwaliteit van Leven (author)
We report a sensitive, generic method for quantitative profiling of bile acids and other endogenous metabolites in small quantities of various biological fluids and tissues. The method is based on a straightforward sample preparation, separation by reversed-phase high performance liquid-chromatography mass spectrometry (HPLC-MS) and electrospray...
article 2008
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Korsheninnikova, E. (author), van der Zon, G.C.M. (author), Voshol, P.J. (author), Janssen, G.M. (author), Havekes, L.M. (author), Grefhorst, A. (author), Kuipers, F. (author), Reijngoud, D.-J. (author), Romijn, J.A. (author), Ouwens, D.M. (author), Maassen, J.A. (author), TNO Kwaliteit van Leven (author)
Aims/hypothesis: Activation of nutrient sensing through mammalian target of rapamycin (mTOR) has been linked to the pathogenesis of insulin resistance. We examined activation of mTOR-signalling in relation to insulin resistance and hepatic steatosis in mice. Materials and methods: Chronic hepatic steatosis and hepatic insulin resistance were...
article 2006
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den Boer, M.A.M. (author), Voshol, P.J. (author), Kuipers, F. (author), Romijn, J.A. (author), Havekes, L.M. (author), TNO Kwaliteit van Leven (author)
Insulin is an important inhibitor of both hepatic glucose output and hepatic VLDL-triglyceride (VLDL-TG) production. We investigated whether both processes are equally sensitive to insulin-mediated inhibition. To test this, we used euglycemic clamp studies with four increasing plasma concentrations of insulin in wild-type C57Bl/6 mice. By...
article 2006
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Post, S.M. (author), Groenendijk, M. (author), van der Hoogt, C.C. (author), Fievet, C. (author), Luc, G. (author), Hoekstra, M. (author), Princen, H.M.G. (author), Staels, B. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
OBJECTIVE - High-density lipoprotein (HDL) plays a key role in protection against development of atherosclerosis by reducing inflammation, protecting against LDL oxidation, and promoting reverse cholesterol transport from peripheral tissues to the liver for secretion into bile. Cholesterol 7α-hydroxylase (Cyp7a1) catalyzes the rate-limiting step...
article 2006
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Kypreos, K.E. (author), van Dijk, K.W. (author), Havekes, L.M. (author), Zannis, V.I. (author), TNO Kwaliteit van Leven (author)
To identify the residues in the carboxyl-terminal region 260-299 of human apolipoprotein E (apoE) that contribute to hypertriglyceridemia, two sets of conserved, hydrophobic amino acids between residues 261 and 283 were mutated to alanines, and recombinant adenoviruses expressing these apoE mutants were generated. Adenovirus-mediated gene...
article 2005
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Goudriaan, J.R. (author), den oer, M.A.M. (author), Rensen, P.C.N. (author), Febbraio, M. (author), Kuipers, F. (author), Romijn, J.A. (author), Havekes, L.M. (author), Voshol, P.J. (author), TNO Kwaliteit van Leven (author)
CD36 is involved in high-affinity peripheral FFA uptake. CD36-deficient (cd36-/-) mice exhibit increased plasma FFA and triglyceride (TG) levels. The aim of the present study was to elucidate the cause of the increased plasma TG levels in cd36-/- mice. cd36-/- mice showed no differences in hepatic VLDL-TG production or intestinal [3H]TG uptake...
article 2005
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Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Sundararaman, D. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)
Studies in humans and mice have shown that increased expression of apolipoprotein C-I (apoC-I) results in combined hyperlipidemia with a more pronounced effect on triglycerides (TGs) compared with total cholesterol (TC). The aim of this study was to elucidate the main reason for this effect using human apoC-I-expressing (APOC1) mice. Moderate...
article 2005
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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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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), TNO Kwaliteit van Leven (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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Post, S.M. (author), Groenendijk, M. (author), Solaas, K. (author), Rensen, P.C.N. (author), Princen, H.M.G. (author), TNO Preventie en Gezondheid (author)
Objective-Cholesterol 7α-hydroxylase (cyp7a1) catalyzes the rate-limiting step in conversion of cholesterol to bile acids. To study the relationship between bile acid biosynthesis and triglyceride metabolism, we cross-bred mice lacking cyp7a1 on a hyperlipidemic APOE*3-Leiden background. Methods and Results-Female mice received a chow or...
article 2004
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Schaap, F.G. (author), Rensen, P.C.N. (author), Voshol, P.J. (author), Vrins, C. (author), van der Vliet, H.N. (author), Chamuleau, R.A.F.M. (author), Havekes, L.M. (author), Groen, A.K. (author), van Dijk, K.W. (author), TNO Preventie en Gezondheid (author)
ApoAV has been discovered recently as a novel modifier of triglyceride (TG) metabolism, but the pathways involved are currently unknown. To gain insight into the function of apoAV, adenovirus-mediated gene transfer of murine apoa5 to C57Bl/6 mice was employed. The injection of low doses of Ad-apoa5 (1-5 x 108 plaque-forming units/mouse) dose...
article 2004
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Orešič, M. (author), Clish, C.B. (author), Davidov, E.J. (author), Verheij, E. (author), Vogels, J. (author), Havekes, L.M. (author), Neumann, E. (author), Adourian, A. (author), Naylor, S. (author), van der Greef, J. (author), Plasterer, T. (author), TNO Preventie en Gezondheid (author)
Multifactorial diseases present a significant challenge for functional genomics. Owing to their multiple compartmental effects and complex biomolecular activities, such diseases cannot be adequately characterised by changes in single components, nor can pathophysiological changes be understood by observing gene transcripts alone. Instead, a...
article 2004
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Espirito Santo, S.M.S. (author), Pires, N.M.M. (author), Boesten, L.S.M. (author), Gerritsen, G. (author), Bovenschen, N. (author), van Dijk, K.W. (author), Jukema, J.W. (author), Princen, H.M.G. (author), Bensadoun, A. (author), Li, W.P. (author), Herz, J. (author), Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Gaubius Instituut TNO (author)
The low-density lipoprotein (LDL) receptor-related protein (LRP) has a well-established role in the hepatic removal of atherogenic apolipoprotein E (APOE)-rich remnant lipoproteins from plasma. In addition, LRP recognizes multiple distinct pro- and antiatherogenic ligands in vitro. Here, we investigated the role of hepatic LRP in atherogenesis...
article 2004
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Gervois, P. (author), Kleemann, R. (author), Pilon, A. (author), Percevault, F. (author), Koenig, W. (author), Staels, B. (author), Kooistra, T. (author), TNO Preventie en Gezondheid (author)
The peroxisome proliferator-activated receptor α (PPARα), which is highly expressed in liver, plays key roles in lipid metabolism and inflammation. Interleukin-6 (IL-6) is the principal inducer of acute phase response (APR) gene expression. In the present study, we demonstrate that chronic treatment with the PPARα agonist fenofibrate fully...
article 2004
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Heijne, W.H.M. (author), Slitt, A.L. (author), van Bladeren, P.J. (author), Groten, J.P. (author), Klaassen, C.D. (author), Stierum, R.H. (author), van Ommen, B. (author), TNO Voeding Centraal Instituut voor Voedingsonderzoek TNO (author)
Rats were exposed to three levels of bromobenzene, sampled at 6, 24, and 48 h, and liver gene expression profiles were determined to identify dose and time-related changes. Expression of many genes changed transiently, and dependent on the dose. Few changes were identified after 6 h, but many genes were differentially expressed after 24 h, while...
article 2004
Searched for: subject:"Animals"
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