Chylomicron Margination, Lipolysis, and Vitamin A Uptake in the Lactating Rat Mammary Gland: Implications for Milk Retinoid Content

Ross, A. Catharine; Pasatiempo, A. M. G.; Green, Michael H.

doi:10.1177/153537020422900106

Cited by 52 publications

(40 citation statements)

References 35 publications

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“…Core radioactivity, that traces the particles, rose gradually to a maximum at 7 min and then decreased rapidly. If the residence time for chylomicrons at endothelial binding sites was only a few seconds there would be an almost immediate peak, followed by a decay that paralleled recent study by Ross, Pasatiempo, and Green ( 18 ). They compared the binding of chylomicrons in mammary glands of lactating rats, that have high LPL activity, and 1 day after the litter had been removed, when LPL has dropped to a much lower level ( 19 ).…”

Section: Discussionmentioning

confidence: 48%

“…Circles, core label and remnants enter the liver with similar rate constants, in contrast to the marked difference noted for heart and adipose tissue where remnants showed much reduced binding affi nity. Hydrolysis of chylomicron TGs in the liver presumably occurs mainly in endosomes and lysosomes ( 7,17,18 ). We therefore tested the impact of a lag compartment before the fatty acids became available for oxidation or return to blood as FFAs.…”

Section: Livermentioning

confidence: 99%

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Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes

Hultin

Savonen

Chevreuil

et al. 2013

Journal of Lipid Research

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( 7 ). One approach to study these processes is compartmental modeling, which allows for testing of hypotheses regarding the structure of the system and for calculations of residence times and fl uxes ( 8 ). In a previous study we used compartmental modeling to study the disappearance of chylomicron lipids from the circulating blood ( 6 ). The results indicated that a large fraction of chylomicron TGs leaves plasma with the particles, and that most of the fatty acids from chylomicron TGs mix into the same metabolic compartment as do plasma FFAs. That study was based on data for radioactivity in blood lipids. In the present study we focus on the binding/sequestration of chylomicrons in tissues, and the subsequent fate of the particles and their lipids. This is based on data for radioactivity in tissues at a series of short times after injection of doubly labeled chylomicrons. The major questions asked were: What is the nature of the interaction of chylomicron particles with the vascular endothelium? Are the interactions short-lived so that there is in effect near-equilibrium between particles in blood and at the endothelium or is the interaction of a chylomicron particle with an endothelial binding-lipolysis site more long-lived? If so, can we estimate the residence time? EXPERIMENTAL PROCEDURES Animal proceduresMale Sprague-Dawley rats (150 g), from Moellegaard Breeding Center, Skensved, Denmark, were allowed to acclimatize for at least 1 week after transport before being included in the study. They were allowed free access to water and standard chow and were kept on a 12 h/12 h light/dark cycle with light start at 6:00 AM . At the time of the experiment they weighed 217 ± 13 g (fed)Abstract Chylomicrons labeled in vivo with 14 C -oleic acid (primarily in triglycerides, providing a tracer for lipolysis) and 3 H-retinol (primarily in ester form, providing a tracer for the core lipids) were injected into rats. Radioactivity in tissues was followed at a series of times up to 40 min and the data were analyzed by compartmental modeling. For heartlike tissues it was necessary to allow the chylomicrons to enter into a compartment where lipolysis is rapid and then transfer to a second compartment where lipolysis is slower. The particles remained in these compartments for minutes and when they returned to blood they had reduced affi nity for binding in the tissue. In contrast, the data for liver could readily be fi tted with a single compartment for native and lipolyzed chylomicrons in blood, and there was no need for a pathway back to blood. A composite model was built from the individual tissue models. This whole-body model could simultaneously fi t all data for both fed and fasted rats and allowed estimation of fl uxes and residence times in the four compartments; native and lipolyzed chylomicrons ("remnants") in blood, and particles in the tissue compartments where lipolysis is rapid and slow, respectively. Dietary fat is transported from the intestine in chylomicrons ( 1, 2 ). The metabolism of these is considered t...

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Section: Discussionmentioning

confidence: 48%

Section: Livermentioning

confidence: 99%

Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes

Hultin

Savonen

Chevreuil

et al. 2013

Journal of Lipid Research

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“…Goulbourne et al ( 9 ) have recently shown that this "margination" requires GPIHBP1-bound LPL. There is much previous evidence that the more LPL there is in a tissue, the more chylomicron lipids are taken up there ( 4,17,18 ). This is a direct effect of the lipase molecule as such.…”

Section: Discussionmentioning

confidence: 99%

The tissue distribution of lipoprotein lipase determines where chylomicrons bind

Savonen

Hiden

Hultin

et al. 2015

Journal of Lipid Research

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This article is available online at http://www.jlr.org regulated in a tissue-specifi c manner ( 1, 2 ). As an example, the activity in adipose tissue is relatively low between meals but rises postprandially ( 6 ). This has been suggested to govern when and to what extent lipids are delivered to the adipose tissue for storage ( 1, 2 ). On the other hand, it has been argued that the only role of the enzyme is to release the fatty acids in a form that can be transferred from lipoproteins into cells or onto albumin, and that the amount taken up by individual cells is usually governed by transport processes ( 7 ) and/or the metabolic balance within the cell ( 8 ) rather than by the rate at which the lipase releases fatty acids at endothelial sites adjacent to the cell.The first step in chylomicron catabolism is that the lipoprotein particles bind to the endothelial surface, a process named margination. Goulbourne et al. ( 9 ) have demonstrated that the margination requires LPL bound to GPIHBP1. Defi ciency of GPIHBP1, genetic or in mouse models, leads to equally severe hyperchylomicronemia as defi ciency of LPL itself ( 10 ). In this setting normal amounts of LPL are produced, but do not reach the endothelial surface. Mouse genetic models with altered expression of LPL have been generated. Total LPL defi ciency due to gene knockout leads to lethal hypertriglyceridemia within 18 h of life ( 11 ). By mating heterozygous LPL knockout mice with transgenic mice that express human LPL in either muscle ( 12 ) or heart ( 13 ), mouse lines have been generated that express the enzyme in only a single tissue. Here we have taken advantage of these mouse models to study to what extent the expression of LPL in a tissue governs initial binding and/or deposition of lipids in that tissue . For this we used rat chylomicrons, labeled in vivo with [3 H]-retinol (which is incorporated into retinyl esters and serves as label for the core lipids and for the chylomicron particles) and [ ]retinol (primarily in ester form, providing a tracer for the core lipids) were injected. TG label was cleared more rapidly than core label. There were no differences between the mouse lines in the rate at which core label was cleared. Two minutes after injection, about 5% of the core label, and hence chylomicron particles, were in the heart of WT mice. In mice that expressed LPL only in skeletal muscle, and had much reduced levels of LPL in the heart, binding of chylomicrons was reduced to 1%, whereas in mice that expressed LPL only in the heart, the binding was increased to over 10%. The same patterns of distribution were evident at 20 min when most of the label had been cleared. Thus, the amount of LPL expressed in muscle and heart governed both the binding of chylomicron particles and the assimilation of chylomicron lipids in the tissue.

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“…25 Under this condition, and also in face of basal VA ingestion, it is suggested that less than 70% of retinol found in milk is transferred to mammary gland through RBP and around 30% through chylomicrons; 23,26 for such hepatic reserves must be severely depleted for limiting the availability of the retinol to be secreted through holo-RBP. 24 Chylomicrons' contribution, on its turn, will be increased under conditions of increasing VA ingestion or supplementation, this fact being a consequence of the intensification of lipoprotein lipase in mammary gland during delivery and lactation. 23,27 Two mechanisms are also responsible for VA transference from mother to infant: placenta during gestation and mammary gland (breast milk) during lactation.…”

Section: Vitamin A: Metabolism and Functionsmentioning

confidence: 99%

“…However, it is known that in animal models, VA is transferred to milk in two ways: retinol-RBP complex and chylomicrons. 23,24 Retinol-RBP complex is responsible for more than 95% of the VA present in the circulation at fasting states. 25 Under this condition, and also in face of basal VA ingestion, it is suggested that less than 70% of retinol found in milk is transferred to mammary gland through RBP and around 30% through chylomicrons; 23,26 for such hepatic reserves must be severely depleted for limiting the availability of the retinol to be secreted through holo-RBP.…”

Section: Vitamin A: Metabolism and Functionsmentioning

confidence: 99%

Vitamina A e diabetes gestacional

Lira¹,

Dimenstein²

2010

Rev. Assoc. Med. Bras.

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Chylomicron Margination, Lipolysis, and Vitamin A Uptake in the Lactating Rat Mammary Gland: Implications for Milk Retinoid Content

Cited by 52 publications

References 35 publications

Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes

Chylomicron metabolism in rats: kinetic modeling indicates that the particles remain at endothelial sites for minutes

The tissue distribution of lipoprotein lipase determines where chylomicrons bind

Vitamina A e diabetes gestacional

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