β-VLDL accumulation in familial dysbetalipoproteinemia is associated with increased exchange or diffusion of chylomicron lipids to apo B-100 containing triglyceride-rich lipoproteins

Demacker, P.N.M.; Bredie, S.J.H.; Vogelaar, J.M.; Hectors, M. P. C.; Heijst, Pieternel van; Stuyt, P.M.J.; Stalenhoef, Anton F. H.

doi:10.1016/s0021-9150(98)00035-5

Cited by 10 publications

(3 citation statements)

References 55 publications

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“…We presume this was due to a defect in lipoprotein lipase, which is thought to be a major reason for the hypertriglyceridemia of diabetes [27]. It would be expected that an excess of triglyceride-rich lipoproteins in the circulation would delay clearance of injected triglyceride-rich particles due to competition for receptors [28] and of course we had a 5-fold increase in plasma triglyceride in the diabetic recipient animals. We found a positive correlation between blood sugar on the day of experiment and triglyceride retention time, again suggesting a relationship with insulin deficiency.…”

Section: Discussionmentioning

confidence: 99%

Defective Chylomicron Synthesis as a Cause of Delayed Particle Clearance in Diabetes?

Phillips

Madigan

Owens

et al. 2002

Journal of Diabetes Research

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Chylomicron metabolism is abnormal in diabetes and the chylomicron particle may play a very important role in atherosclerosis. The aim of this study was to examine the effect of diabetes on the metabolism of chylomicrons in cholesterol-fed alloxan diabetic and nondiabetic rabbits. Five diabetic rabbits and 5 control rabbits were given [14C]linoleic acid and [3H]cholesterol by gavage. Lymph was collected following cannulation of the lymph duct and radiolabelled chylomicrons were isolated by ultracentrifugation. The chylomicrons from each animal were injected into paired control and diabetic recipients. Lymph apolipoprotein (apo) B48, apo B100, and apo E were measured using sodium dodecyl sulfate–polyacrylamide gradient gel electrophoresis. Mean blood sugar of the diabetic donors and diabetic recipients were 19.7 ± 2.3 and 17.2 ± 3.2 mmol/L. Diabetic rabbits had significantly raised plasma triglyceride (10.8 ± 13.9 versus 0.8 ± 0.5 mmol/L, P < 0.02). There was a large increase in apo B48 in lymph chylomicrons in the diabetic donor animals (0.19 ± 0.10 versus 0.04 ± 0.02 mg/h, P < 0.01) and apo B100 (0.22 ± 0.15 versus 0.07 ± 0.07 mg/h, P < 0.05) and a reduction in apo E on the lymph chylomicron particle (0.27 ± 0.01 versus 0.62 ± 0.07 mg/mg apo B, P < 0.001). Diabetic recipients cleared both control and diabetic chylomicron triglyceride significantly more slowly than control recipients (P < 0.05). Clearance of control chylomicron cholesterol was delayed when injected into diabetic recipients compared to when these chylomicrons were injected into control recipients (P < 0.005). Clearance of diabetic chylomicron cholesterol was significantly slower when injected into control animals compared to control chylomicron injected into control animals (P < 0.02). In this animal model of atherosclerosis, we have demonstrated that diabetes leads to the production of an increased number of lipid and apo E–deficient chylomicron particles. Chylomicron particles from the control animals were cleared more slowly by the diabetic recipient (both triglyceride and cholesterol). The chylomicron particles obtained from the diabetic animals were cleared even more slowly when injected into the diabetic recipient. Although there was an initial delay in clearance of chylomicron triglyceride from the diabetic particle when injected into the control animals, the clearance over the first 15 minutes was not significantly different when compared to the control chylomicron injected into the control animal. On the other hand, the cholesterol clearance was significantly delayed. Thus, diabetes resulted in the production of an increased number of lipid- and apo E–deficient chylomicron particles. These alterations account, in part, for the delay in clearance of these particles.

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Section: Discussionmentioning

confidence: 99%

Defective Chylomicron Synthesis as a Cause of Delayed Particle Clearance in Diabetes?

Phillips

Madigan

Owens

et al. 2002

Journal of Diabetes Research

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“…However, severe lipemia is is most commonly associated with a deficiency of lipoprotein lipase (LPL) or apoC II, and significantly elevated CM and CM remnants are detected in the fasting plasma of these cases (7). Type III hyperlipidemia is a kind of postprandial genetic defect which results in significantly elevated apoB48 in beta-VLDL and is associated with the low affinity of apoE2/2 for the receptors which clear remnant lipoproteins (8–11). Alimentary lipemia is often reflected by the increased turbidity of fat emulsions, not CM, in plasma in terms of lipid concentrations.…”

Section: Introductionmentioning

confidence: 99%

Postprandial lipoprotein metabolism: VLDL vs chylomicrons

Nakajima¹,

Nakano²,

Tokita³

et al. 2011

Clinica Chimica Acta

134

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Since Zilversmit first proposed postprandial lipemia as the most common risk of cardiovascular disease, chylomicrons (CM) and CM remnants have been thought to be the major lipoproteins which are increased in the postprandial hyperlipidemia. However, it has been shown over the last two decades that the major increase in the postprandial lipoproteins after food intake occurs in the very low density lipoprotein (VLDL) remnants (apoB100 particles), not CM or CM remnants (apoB48 particles). This finding was obtained using the following three analytical methods; isolation of remnant-like lipoprotein particles (RLP) with specific antibodies, separation and detection of lipoprotein subclasses by gel permeation HPLC and determination of apoB48 in fractionated lipoproteins by a specific ELISA. The amount of the apoB48 particles in the postprandial RLP is significantly less than the apoB100 particles, and the particle sizes of apoB48 and apoB100 in RLP are very similar when analyzed by HPLC. Moreover, CM or CM remnants having a large amount of TG were not found in the postprandial RLP. Therefore, the major portion of the TG which is increased in the postprandial state is composed of VLDL remnants, which have been recognized as a significant risk for cardiovascular disease.

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“…These cases often have a deficiency of lipoprotein lipase (LPL) or apoC-II (activator of LPL). Type III hyperlipidemia also results in significantly increased apoB-48 in beta-VLDL due to a genetic defect associated with the low affinity of apoE2/2 for hepatic receptors that clear remnant lipoproteins [8][9][10][11].…”

Section: Introductionmentioning

confidence: 99%