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Sleep duration and lipid metabolism in patients with diabetes mellitus: from the POWER2DM study

Perez‑Corral, I. (author), Gomez‑Delgado, F. (author), Ruissen, M.M. (author), Torres‑Peña1, J.D. (author), Larriva Arenas-de, A.P. (author), Sont, J.K. (author), de Graaf, A.A. (author), Uitbeijerse, B.S. (author), de Koning, E.J.P. (author), Delgado-Lista, J. (author)

This study assesses the association between sleep duration and plasma lipid profiles in people with diabetes mellitus (DM). Sleep duration data were obtained in 91 patients from the POWER2DM study (NCT03588104). The patients were divided in tertiles, based on their sleep duration, and blood samples were obtained at the beginning and after 9...

article 2022

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Atorvastatin accelerates clearance of lipoprotein remnants generated by activated brown fat to further reduce hypercholesterolemia and atherosclerosis

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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Ranges of phenotypic flexibility in healthy subjects

van den Broek, T.J. (author), Bakker, G.C.M. (author), Rubingh, C.M. (author), Bijlsma, S. (author), Stroeve, J.H.M. (author), van Ommen, B. (author), van Erk, M.J. (author), Wopereis, S. (author)

Background: A key feature of metabolic health is the ability to adapt upon dietary perturbations. A systemic review defined an optimal nutritional challenge test, the "PhenFlex test" (PFT). Recently, it has been shown that the PFT enables the quantification of all relevant metabolic processes involved in maintaining or regaining homeostasis of...

article 2017

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Weight loss predictability by plasma metabolic signatures in adults with obesity and morbid obesity of the DiOGenes study

Stroeve, J.H.M. (author), Saccenti, E. (author), Bouwman, J. (author), Dane, A. (author), Strassburg, K. (author), Vervoort, J. (author), Hankemeier, T. (author), Astrup, A. (author), Smilde, A.K. (author), van Ommen, B. (author), Saris, W.H.M. (author)

Objective: Aim is to predict successful weight loss by metabolic signatures at baseline and to identify which differences in metabolic status may underlie variations in weight loss success. Methods: In DiOGenes, a randomized, controlled trial, weight loss was induced using a low calorie diet (800 kcal) for 8-weeks. Men (N5236) and women (N5431)...

article 2016

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Anacetrapib reduces progression of atherosclerosis, mainly by reducing non-HDL-cholesterol, improves lesion stability and adds to the beneficial effects of atorvastatin

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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Salsalate attenuates diet induced non-alcoholic steatohepatitis in mice by decreasing lipogenic and inflammatory processes

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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Innovative pharmaceutical interventions in cardiovascular disease: Focusing on the contribution of non-HDL-C/LDL-C-lowering versus HDL-C-raisingA systematic review and meta-analysis of relevant preclinical studies and clinical trials

Kühnast, S. (author), Fiocco, M. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author)

Non-HDL-cholesterol is well recognised as a primary causal risk factor in cardiovascular disease. However, despite consistent epidemiological evidence for an inverse association between HDL-C and coronary heart disease, clinical trials aimed at raising HDL-C (AIM-HIGH, HPS2-THRIVE, dal-OUTCOMES) failed to meet their primary goals. This...

article 2015

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Drugs that reverse disease transcriptomic signatures are more effective in a mouse model of dyslipidemia

Wagner, A. (author), Cohen, N. (author), Kelder, T. (author), Amit, U. (author), Liebman, E. (author), Steinberg, D.M. (author), Radonjic, M. (author), Ruppin, E. (author)

High-throughput omics have proven invaluable in studying human disease, and yet day-to-day clinical practice still relies on physiological, non-omic markers. The metabolic syndrome, for example, is diagnosed and monitored by blood and urine indices such as blood cholesterol levels. Nevertheless, the association between the molecular and the...

article 2015

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Predicting individual responses to pravastatin using a physiologically based kinetic model for plasma cholesterol concentrations

van de Pas, N.C.A. (author), Rullmann, J.A.C. (author), Woutersen, R.A. (author), van Ommen, B. (author), Rietjens, I.M.C.M. (author), de Graaf, A.A. (author)

We used a previously developed physiologically based kinetic (PBK) model to analyze the effect of individual variations in metabolism and transport of cholesterol on pravastatin response. The PBK model is based on kinetic expressions for 21 reactions that interconnect eight different body cholesterol pools including plasma HDL and non-HDL...

article 2014

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Effect of moderate alcohol consumption on fetuin-A levels in men and women: Post-hoc analyses of three open-label randomized crossover trials

Joosten, M.M. (author), Schrieks, I.C. (author), Hendriks, H.F.J. (author)

Background: Fetuin-A, a liver-derived glycoprotein that impairs insulin-signalling, has emerged as a biomarker for diabetes risk. Although moderate alcohol consumption has been inversely associated with fetuin-A, data from clinical trials are lacking. Thus, we evaluated whether moderate alcohol consumption decreases circulating levels of fetuin...

article 2014

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The Netherlands twin register biobank: A resource for genetic epidemiological studies

Willemsen, G. (author), de Geus, E.J.C. (author), Bartels, M. (author), van Beijsterveldt, C.E.M.T. (author), Brooks, A.I. (author), Estourgie-van Burk, G.F. (author), Fugman, D.A. (author), Hoekstra, C. (author), Hottenga, J.-J. (author), Kluft, K. (author), Meijer, P. (author), Montgomery, G.W. (author), Rizzu, P. (author), Sondervan, D. (author), Smit, A.B. (author), Spijker, S. (author), Suchiman, H.E.D. (author), Tischfield, J.A. (author), Lehner, T. (author), Slagboom, P.E. (author), Boomsma, D.I. (author), TNO Kwaliteit van Leven (author)

In 2004 the Netherlands Twin Register (NTR) started a large scale biological sample collection in twin families to create a resource for genetic studies on health, lifestyle and personality. Between January 2004 and July 2008, adult participants from NTR research projects were invited into the study. During a home visit between 7:00 and 10:00 am...

article 2010

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The association of 83 plasma proteins with CHD mortality, BMI, HDL-, and total-cholesterol in men: Applying multivariate statistics to identify proteins with prognostic value and biological relevance

Geert Heidema, A. (author), Thissen, U. (author), Boer, J.M.A. (author), Bouwman, F.G. (author), Feskens, E.J.M. (author), Mariman, E.C.M. (author), TNO Kwaliteit van Leven (author)

In this study, we applied the multivariate statistical tool Partial Least Squares (PLS) to analyze the relative importance of 83 plasma proteins in relation to coronary heart disease (CHD) mortality and the intermediate end points body mass index, HDL-cholesterol and total cholesterol. From a Dutch monitoring project for cardiovascular disease...

article 2009

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The dual PPARα/γ agonist tesaglitazar blocks progression of pre-existing atherosclerosis in APOE*3Leiden.CETP transgenic mice

van der Hoorn, J.W.A. (author), Jukema, J.W. (author), Havekes, L.M. (author), Lundholm, E. (author), Camejo, G. (author), Rensen, P.C.N. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)

Background and purpose: We have evaluated the effects of a peroxisome proliferator-activated receptor (PPAR)α/γ agonist on the progression of pre-existing atherosclerotic lesions in APOE*3Leiden.cholesteryl ester transfer protein (E3L.CETP) transgenic mice. Experimental approach: E3L.CETP mice were fed a high-cholesterol diet for 11 weeks to...

article 2009

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Apolipoprotein CI inhibits scavenger receptor BI and increases plasma HDL levels in vivo

de Haan, W. (author), Out, R. (author), Berbée, J.F.P. (author), van der Hoogt, C.C. (author), Dijk, K.W.v. (author), van Berkel, T.J.C. (author), Romijn, J.A. (author), Wouter Jukema, J. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), TNO Kwaliteit van Leven (author)

Apolipoprotein CI (apoCI) has been suggested to influence HDL metabolism by activation of LCAT and inhibition of HL and CETP. However, the effect of apoCI on scavenger receptor BI (SR-BI)-mediated uptake of HDL-cholesteryl esters (CE), as well as the net effect of apoCI on HDL metabolism in vivo is unknown. Therefore, we evaluated the effect of...

article 2008

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Plasma apolipoprotein CI protects against mortality from infection in old age

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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Moderate alcohol consumption and lipoprotein-associated phospholipase A2 activity

Beulens, J.W.J. (author), van den Berg, R. (author), Kok, F.J. (author), Helander, A. (author), Vermunt, S.H.F. (author), Hendriks, H.F.J. (author), TNO Kwaliteit van Leven (author)

Background and aims: To investigate the effect of moderate alcohol consumption on lipoprotein-associated phospholipase A2 activity, markers of inflammation and oxidative stress and whether these effects are modified by BMI. Methods and results: Eleven lean (BMI: 18.5-25 kg/m2) and 9 overweight (BMI > 27 kg/m2) men participated in a randomized...

article 2008

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Lipidomic approach to evaluate rosuvastatin and atorvastatin at various dosages: Investigating differential effects among statins

Bergheanu, S.C. (author), Reijmers, T. (author), Zwinderman, A.H. (author), Bobeldijk, I. (author), Ramaker, R. (author), Liem, A.-H. (author), van der Greef, J. (author), Hankemeier, T. (author), Jukema, J.W. (author), TNO Kwaliteit van Leven (author)

Objective: Lipid profiling (lipidomics) may be useful in revealing detailed information with regard to the effects on lipid metabolism, the cardiovascular risk and to differentiate between therapies. The aims of the present study were to: (1) analyze in depth the lipid changes induced by rosuvastatin and atorvastatin at different dosages; (2)...

article 2008

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Atorvastatin increases HDL cholesterol by reducing CETP expression in cholesterol-fed APOE*3-Leiden.CETP mice

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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Niacin increases HDL by reducing hepatic expression and plasma levels of cholesteryl ester transfer protein in APOE*3Leiden.CETP mice

van der Hoorn, J.W.A. (author), de Haan, W. (author), Berbée, J.P.P. (author), Havekes, L.M. (author), Jukema, J.W. (author), Rensen, P.C. (author), Princen, H.M.G. (author), TNO Kwaliteit van Leven (author)

Objective - Niacin potently decreases plasma triglycerides and LDL-cholesterol. In addition, niacin is the most potent HDL-cholesterol- increasing drug used in the clinic. In the present study, we aimed at elucidation of the mechanism underlying its HDL-raising effect. Methods and Results - InAPOE*3Leiden transgenic mice expressing the human...

article 2008

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Plasma apolipoprotein CI correlates with increased survival in patients with severe sepsis

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