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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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Kooijman, S. (author), Meurs, I. (author), van der Stoep, M. (author), Habets, K.L. (author), Lammers, B. (author), Berbée, J.F.P. (author), Havekes, L.M. (author), van Eck, M. (author), Romijn, J.A. (author), Korporaal, S.J.A. (author), Rensen, P.C.N. (author)
Summary: Background: The autonomic nervous system attenuates inflammation through activation of the α7 nicotinic acetylcholine receptor (α7nAChR), a pathway termed the cholinergic anti-inflammatory reflex. Interestingly, α7nAChR is expressed on immune cells and platelets, both of which play a crucial role in the development of atherosclerosis....
article 2015
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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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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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Geerling, J.J. (author), Boon, M.R. (author), van der Zon, G.C. (author), van den Berg, S.A.A. (author), van den Hoek, A.M. (author), Lombès, M. (author), Princen, H.M.G. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Guigas, B. (author)
Metformin is the first-line drug for the treatment of type 2 diabetes. Besides its well-characterized antihyperglycemic properties, metformin also lowers plasma VLDL triglyceride (TG). In this study, we investigated the underlying mechanisms in APOE*3-Leiden.CETP mice, a well-established model for human-like lipoprotein metabolism. We found that...
article 2014
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Geerling, J.J. (author), Boon, M.R. (author), Kooijman, S. (author), Parlevliet, E.T. (author), Havekes, L.M. (author), Romijn, J.A. (author), Meurs, I.M. (author), Rensen, P.C.N. (author)
Abstract Important players in triglyceride (TG) metabolism include the liver (production), white adipose tissue (WAT) (storage), heart and skeletal muscle (combustion to generate ATP), and brown adipose tissue (BAT) (combustion toward heat), the collective action of which determine plasma TG levels. Interestingly, recent evidence points to a...
article 2014
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Heemskerk, M.M. (author), van den Berg, S.A. (author), Pronk, A.C.M. (author), van Klinken, J.B. (author), Boon, M.R. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), Willems van Dijk, K. (author), van Harmelen, V. (author)
The lipid-lowering effect of niacin has been attributed to the inhibition of cAMP production in adipocytes, thereby inhibiting intracellular lipolysis and release of nonesterified fatty acids (NEFA) to the circulation. However, long-term niacin treatment leads to a normalization of plasma NEFA levels and induces insulin resistance, for which the...
article 2014
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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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Bakker, L.E.H. (author), Boon, M.R. (author), van der Linden, R.A.D. (author), Arias-Bouda, L.P. (author), van Klinken, J.B. (author), Smit, F. (author), Verberne, H.J. (author), Jukema, J.W. (author), Tamsma, J.T. (author), Havekes, L.M. (author), van Marken Lichtenbelt, W.D. (author), Jazet, I.M. (author), Rensen, P.C.N. (author)
Background: Individuals of south Asian origin have a very high risk of developing type 2 diabetes compared with white Caucasians. We aimed to assess volume and activity of brown adipose tissue (BAT), which is thought to have a role in energy metabolism by combusting fatty acids and glucose to produce heat and might contribute to the difference...
article 2014
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Wang, Y. (author), Parlevliet, E.T. (author), Geerling, J.J. (author), van der Tuin, S.J.L. (author), Zhang, H. (author), Bieghs, V. (author), Jawad, A.H.M. (author), Shiri-Sverdlov, R. (author), Bot, I. (author), de Jager, S.C.A. (author), Havekes, L.M. (author), Romijn, J.A. (author), Willems Van Dijk, K. (author), Rensen, P.C.N. (author)
Background and Purpose The aetiology of inflammation in the liver and vessel wall, leading to non-alcoholic steatohepatitis (NASH) and atherosclerosis, respectively, shares common mechanisms including macrophage infiltration. To treat both disorders simultaneously, it is highly important to tackle the inflammatory status. Exendin-4, a glucagon...
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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Gautier, T. (author), de Haan, W. (author), Grober, J. (author), Ye, D. (author), Bahr, M.J. (author), Claudel, T. (author), Nijstad, N. (author), van Berkel, T.J. (author), Havekes, L.M. (author), Manns, M.P. (author), Willems, S.M. (author), Hogendoorn, P.C. (author), Lagrost, L. (author), Kuipers, F. (author), van Eck, M. (author), Rensen, P.C. (author), Tietge, U.J. (author)
Cholesteryl ester transfer protein (CETP) activity results in a proatherogenic lipoprotein profi le. In cholestatic conditions, farnesoid X receptor (FXR) signaling by bile acids (BA) is activated and plasma HDL cholesterol (HDL-C) levels are low. This study tested the hypothesis that FXR-mediated induction of CETP contributes to this phenotype....
article 2013
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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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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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Geerling, J.J. (author), Wang, Y. (author), Havekes, L.M. (author), Romijn, J.A. (author), Rensen, P.C.N. (author)
Objective: Central neuropeptide Y (NPY) administration stimulates food intake in rodents. In addition, acute modulation of central NPY signaling increases hepatic production of very low-density lipoprotein (VLDL)-triglyceride (TG) in rats. As hypertriglyceridemia is an important risk factor for atherosclerosis, for which well-established mouse...
article 2013
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Kühnast, S. (author), Louwe, M.C. (author), Heemskerk, M.M. (author), Pieterman, E.J. (author), van Klinken, J.B. (author), van den Berg, S.A.A. (author), Smit, J.W.A. (author), Havekes, L.M. (author), Rensen, P.C.N. (author), van der Hoorn, J.W.A. (author), Princen, H.M.G. (author), Jukema, J.W. (author)
Objective:Niacin potently lowers triglycerides, mildly decreases LDL-cholesterol, and largely increases HDL-cholesterol. Despite evidence for an atheroprotective effect of niacin from previous small clinical studies, the large outcome trials, AIM-HIGH and HPS2-THRIVE did not reveal additional beneficial effects of niacin (alone or in combination...
article 2013
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Auvinen, H.E. (author), Wang, Y. (author), Princen, H. (author), Romijn, J.A. (author), Havekes, L.M. (author), Smit, J.W.A. (author), Meijer, O.C. (author), Biermasz, N.R. (author), Rensen, P.C.N. (author), Pereira, A.M. (author)
Introduction: The role of glucocorticoids in atherosclerosis development is not clearly established. Human studies show a clear association between glucocorticoid excess and cardiovascular disease, whereas most animal models indicate an inhibitory effect of glucocorticoids on atherosclerosis development. These animal models, however, neither...
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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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-1β 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 feces...
article 2013
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Berbée, J.F.P. (author), Wong, M.C. (author), Wang, Y. (author), van der Hoorn, J.W.A. (author), Khedoe, P.P.S.J. (author), van Klinken, J.B. (author), Mol, I.M. (author), Hiemstra, P.S. (author), Tsikas, D. (author), Romijn, J.A. (author), Havekes, L.M. (author), Princen, H.M.G. (author), Rensen, P.C.N. (author)
Resveratrol is a major constituent of traditional Asian medicinal herbs and red wine and is suggested to be a potential antiatherosclerotic drug due to its proposed hypolipidemic, anti-inflammatory and antioxidative properties. The aim of this study was to evaluate whether resveratrol protects against atherosclerosis development in APOE*. 3...
article 2013
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