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Apolipoprotein C-I binds free fatty acids and reduces their intracellular esterification

TNO Kwaliteit van Leven (author), 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)

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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Apolipoprotein CI overexpression is not a relevant strategy to block cholesteryl ester transfer protein (CETP) activity in CETP transgenic mice

TNO Kwaliteit van Leven (author), Gautier, T. (author), Masson, D. (author), Jong, M.C. (author), Pais De Barros, J.P. (author), Duverneuil, L. (author), Le Guern, N. (author), Deckert, V. (author), Dumont, L. (author), Bataille, A. (author), Zak, Z. (author), Jiang, X.C. (author), Havekes, L.M. (author), Lagrost, L. (author)

ApoCI (apolipoprotein CI) is a potent inhibitor of plasma CETP [CE (cholesteryl ester) transfer protein]. The relevance of apoCI overexpression as a method for CETP blockade in vivo was addressed in the present study in CETPTg/apoCITg mice (mice expressing both human CETP and apoCI). Despite a significant reduction in specific CETP activity in...

article 2005

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A low-fat diet has a higher potential than energy restriction to improve high-fat diet-induced insulin resistance in mice

Muurling, M. (author), Jong, M.C. (author), Mensink, R.P. (author), Hornstra, G. (author), Dahlmans, V.E.H. (author), Pijl, H. (author), Voshol, P.J. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)

Previous studies have shown that energy restriction (ER) or low-fat (LF) diets have beneficial effects on high-fat (HF) diet-induced obesity and non-insulin-dependent diabetes. However, comparison between ER and low-fat diet regarding the effect on insulin resistance and lipid metabolism has not been reported. After inducing insulin resistance...

article 2002

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Apolipoprotein CI deficiency markedly augments plasma lipoprotein changes mediated by human cholesteryl ester transfer protein (CETP) in CETP transgenic/apoCI-knocked out mice

Gaubius Instituut TNO (author), Gautier, T. (author), Masson, D. (author), Jong, M.C. (author), Duverneuil, L. (author), Guern, N.L. (author), Deckert, V. (author), de Barros, J.P.P. (author), Dumont, L. (author), Bataille, A. (author), Zak, Z. (author), Jiang, X.C. (author), Tall, A.R. (author), Havekes, L.M. (author), Lagrost, L. (author)

Transgenic mice expressing human cholesteryl ester transfer protein (HuCETPTg mice) were crossed with apolipoprotein CI-knocked out (apoCI-KO) mice. Although total cholesterol levels tended to be reduced as the result of CETP expression in HuCETPTg heterozygotes compared with C57BL6 control mice (-13%, not significant), a more pronounced...

article 2002

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Hyperlipidaemia is associated with increased insulin-mediated glucose metabolism, reduced fatty acid metabolism and normal blood pressure in transgenic mice overexpressing human apolipoprotein C1

Koopmans, S.J. (author), Jong, M.C. (author), Que, I. (author), Dahlmans, V.E.H. (author), Pijl, H. (author), Radder, J.K. (author), Frölich, M. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)

Aims/hypothesis. Insulin resistance for glucose metabolism is associated with hyperlipidaemia and high blood pressure. In this study we investigated the effect of primary hyperlipidaemia on basal and insulin-mediated glucose and on non-esterified fatty acid (NEFA) metabolism and mean arterial pressure in hyperlipidaemic transgenic mice...

article 2001

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Protection from obesity in mice lacking the VLDL receptor

Goudriaan, J.R. (author), Tacken, P.J. (author), Dahlmans, V.E.H. (author), Gijbels, M.J.J. (author), van Dijk, K.W. (author), Havekes, L.M. (author), Jong, M.C. (author), Gaubius Instituut TNO (author)

It has previously been reported that mice lacking the VLDL receptor (VLDLR-/-) exhibit normal plasma lipid levels and a modest decrease in adipose tissue mass. In the present study, the effect of VLDLR deficiency on profound weight gain was studied in mice. Obesity was induced either by feeding of a high-fat, high-calorie (HFC) diet or by...

article 2001

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Apolipoprotein C-III deficiency accelerates triglyceride hydrolysis by lipoprotein lipase in wild-type and apoE knockout mice

Gaubius Instituut TNO (author), Jong, M.C. (author), Rensen, P.C.N. (author), Dahlmans, V.E.H. (author), van der Boom, H. (author), van Berkel, T.J.C. (author), Havekes, L.M. (author)

Previous studies with hypertriglyceridemic APOC3 transgenic mice have suggested that apolipoprotein C-III (apoC-III) may inhibit either the apoE-mediated hepatic uptake of TG-rich lipoproteins and/or the lipoprotein lipase (LPL)-mediated hydrolysis of TG. Accordingly, apoC3 knockout (apoC3-/-) mice are hypotriglyceridemic. In the present study,...

article 2001

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Apolipoprotein E2 (Lys146→Gln) causes hypertriglyceridemia due to an apolipoprotein E variant-specific inhibition of lipolysis of very low density lipoproteins-triglycerides

de Beer, F. (author), van Dijk, K.W. (author), Jong, M.C. (author), van Vark, L.C. (author), van der Zee, A. (author), Hofker, M.H. (author), Fallaux, F.J. (author), Hoeben, R.C. (author), Smelt, A.H.M. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)

The apolipoprotein E2 (Lys146→Gln) variant is associated with a dominant form of familial dysbetalipoproteinemia. Heterozygous carriers of this variant have elevated levels of plasma triglycerides, cholesterol, and apolipoprotein E (apoE). It was hypothesized that the high amounts of triglycerides in the very low density lipoprotein (VLDL)...

article 2000

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Cafestol increases serum cholesterol levels in apolipoprotein E*3- leiden transgenic mice by suppression of bile acid synthesis

Post, S.M. (author), de Roos, B. (author), Vermeulen, M. (author), Afman, L. (author), Jong, M.C. (author), Dahlmans, V.E.H. (author), Havekes, L.M. (author), Stellaard, F. (author), Katan, M.B. (author), Princen, H.M.G. (author), Gaubius Instituut TNO (author)

Cafestol, a diterpene present in unfiltered coffee, potently increases serum cholesterol levels in humans. So far, no suitable animal model has been found to study the biochemical background of this effect. We determined the effect of cafestol on serum cholesterol and triglycerides in different mouse strains and subsequently studied its...

article 2000

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Oxidized VLDL induces less triglyceride accumulation in J774 macrophages than native VLDL due to an impaired extracellular lipolysis

Jong, M.C. (author), Hendriks, W.L. (author), van Vark, L.C. (author), Dahlmans, V.E.H. (author), Groener, J.E.M. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)

The present study examined the relative contributions of the different pathways by which oxidatively modified VLDL (oxVLDL) promotes the uptake and intracellular accumulation of lipids in J774 macrophages. VLDL was oxidized for a maximum of 4 hours, resulting in an increase in thiobarbituric acid- reactive substances and an increased...

article 2000

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Apolipoprotein E is resistant to intracellular degradation in vitro and in vivo. Evidence for retroendocytosis

Gaubius instituut TNO (author), Rensen, P.C.N. (author), Jong, M.C. (author), van Vark, L.C. (author), van der Boom, H. (author), Hendriks, W.L. (author), van Berkel, T.J.C. (author), Biessen, E.A.L. (author), Havekes, L.M. (author)

Apolipoprotein E (apoE) is an important determinant for the uptake of triglyceride-rich lipoproteins and emulsions by the liver, but the intracellular pathway of apoE following particle internalization is poorly defined. In the present study, we investigated whether retroendocytosis is a unique feature of apoE as compared with apoB by studying...

article 2000

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Role of apoCs in lipoprotein metabolism: Functional differences between ApoC1, ApoC2, and ApoC3

Jong, M.C. (author), Hofker, M.H. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)

The human apoCs (ie, apoC1, apoC2, and apoC3) are often portrayed as members of 1 consistent protein family because of their similar distributions among lipoprotein classes, their low molecular weights, and coincident purification. The human apoCs are protein constituents of chylomicrons, VLDL, and HDL. In comparison with the intensely studied...

article 1999

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Reversal of hyperlipidaemia in apolipoprotein C1 transgenic mice by adenovirus-mediated gene delivery of the low-density-lipoprotein receptor, but not by the very-low-density-lipoprotein receptor

Gaubius instituut TNO (author), Jong, M.C. (author), Willems-van Dijk, K. (author), Dahlmans, V.E.H. (author), van der Boom, H. (author), Kobayashi, K. (author), Oka, K. (author), Siest, G. (author), Chan, L. (author), Hofker, M.H. (author), Havekes, L.M. (author)

We have shown previously that human apolipoprotein (apo)Cl transgenic mice exhibit hyperlipidaemia, due primarily to an impaired clearance of very-low-density lipoprotein (VLDL) particles from the circulation. In the absence of at least the low-density-lipoprotein receptor (LDLR), it was shown that APOCI overexpression in transgenic mice...

article 1999

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Apolipoprotein E participates in the regulation of very low density lipoprotein-triglyceride secretion by the liver

TNO Preventie en Gezondheid (author), Mensenkamp, A.R. (author), Jong, M.C. (author), van Goor, H. (author), van Luyn, M.J.A. (author), Bloks, V. (author), Havinga, R. (author), Voshol, P.J. (author), Hofker, M.H. (author), van Dijk, K.W. (author), Havekes, L.M. (author), Kuipers, F. (author)

ApoE-deficient mice on low fat diet show hepatic triglyceride accumulation and a reduced very low density lipoprotein (VLDL) triglyceride production rate. To establish the role of apoE in the regulation of hepatic VLDL production, the human APOE3 gene was introduced into apoE-deficient mice by cross-breeding with APOE3 transgenics (APOE3/apoe-/-...

article 1999

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Hyperlipidemia and cutaneous abnormalities in transgenic mice overexpressing human apolipoprotein C1

Jong, M.C. (author), Gijbels, M.J.J. (author), Dahlmans, V.E.H. (author), van Gorp, P.J.J. (author), Koopman, S.-J. (author), Ponec, M. (author), Hofker, M.H. (author), Havekes, L.M. (author), Gaubius instituut TNO (author)

Transgenic mice were generated with different levels of human apolipoprotein C1 (APOC1) expression in liver and skin. At 2 mo of age, serum levels of cholesterol, triglycerides (TG), and FFA were strongly elevated in APOC1 transgenic mice compared with wild-type mice. These elevated levels of serum cholesterol and TG were due mainly to an...

article 1998

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Effects of fenofibrate on hyperlipidemia and postprandial triglyceride metabolism in human apolipoprotein C1 transgenic mice

Jong, M.C. (author), Dahlmans, V.E.H. (author), Princen, H.M.G. (author), Hofker, M.H. (author), Havekes, L.M. (author), Gaubius Instituut TNO (author)

To study the in vivo role of apolipoprotein (apo) C1 in lipoprotein metabolism, we have generated transgenic mice expressing the human apo C1 gene. Apo C1 is a small 6.6 kDa protein that is primarily synthesized by the liver and is present on chylomicrons, very low density lipoproteins (VLDL) and high density lipoproteins (HDL). In recent years,...

article 1998

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Use of transgenic mice in lipoprotein metabolism and atherosclerosis research

Havekes, L.M. (author), van Vlijmen, B.J.M. (author), Jong, M.C. (author), van Dijk, K.W. (author), Hofker, M.H. (author), Gaubius Instituut TNO (author)

In APOE*3-Leiden transgenic mice the atherosclerotic lesion size is correlated with plasma cholesterol. In these mice the plasma lipid levels are positively correlated with the relative amount of APOE 3-Leiden protein on the VLDL particle. The plasma cholesterol levels are influenced by diet, age and gender, mainly due to an effect of these...

article 1997

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Reduced very-low-density lipoprotein fractional catabolic rate in apolipoprotein C1-deficient mice

Jong, M.C. (author), van Ree, J.H. (author), Dahlmans, V.E.H. (author), Frants, R.R. (author), Hofker, M.H. (author), Havekes, L.M. (author), TNO Preventie en Gezondheid (author)

The function of apolipoprotein (apo) C1 in vivo is not clearly defined. Because transgenic mice overexpressing human apoC1 show elevated triacylglycerol (TG) levels, an as yet unknown role for apoC1 in TG metabolism has been suggested. Here we investigated directly the effect of the complete absence of apoC1 on very-low-density lipoprotein (VLDL...

article 1997

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Nascent very-low-density lipoprotein triacylgiycerol hydrolysis by lipoprotein lipase is inhibited by apolipoprotein E in a dose-dependent manner

Gaubius Instituut TNO (author), Jong, M.C. (author), Dahlmans, V.E.H. (author), Hofker, M.H. (author), Havekes, L.M. (author)

In the present study it was investigated whether apolipoprotein (apoE) can inhibit the lipoprotein lipase (LPL)-mediated hydrolysis of very-low-density-lipoprotein (VLDL) triacylglycerols (TAGs). Previous studies have suggested such an inhibitory role for apoE by using as a substrate for LPL either plasma VLDL or artificial TAG emulsions. To...

article 1997

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The role of apolipoprotein C1 and Apolipoprotein E in very low density lipoprotein metabolism as studied in transgenic mouse models

TNO Preventie en Gezondheid (author), Jong, M.C. (author)

doctoral thesis 1997