Hepatic uptake of chylomicron remnants in WHHL rabbits: a mechanism genetically distinct from the low density lipoprotein receptor.
نویسندگان
چکیده
Homozygous Watanabe hereditary hyperlipidemic (WHHL) rabbits have a near-complete deficiency of low density lipoprotein (LDL) receptors in liver and other tissues. As a result, these rabbits clear LDL from plasma at an abnormally slow rate. In the current studies we show that WHHL rabbits clear chylomicrons from plasma at a normal rate. Chylomicrons are cleared by a two-step process: (i) hydrolysis of triglycerides in extrahepatic tissues to yield cholesteryl ester-rich remnant particles and (ii) rapid uptake of the remnants by liver. Normal and WHHL rabbits were given intravenous injections of rat chylomicrons labeled either in the lipid portion with [3H]cholesterol and [14C]palmitate or in the protein portion with [125]iodine. All radiolabeled components were removed from plasma at comparable rates in normal and WHHL rabbits. Comparable amounts of radioactivity accumulated in livers of animals from both genotypes. In vitro assays showed that liver membranes from WHHL rabbits were markedly deficient in the binding of 125I-labeled chylomicron remnants as well as 125I-labeled LDL, implying that chylomicron remnants can bind to the hepatic LDL receptor. We conclude that the rabbit liver normally has at least two genetically distinct lipoprotein uptake mechanisms, both of which recognize chylomicron remnants: (i) the LDL receptor and (ii) a specific chylomicron remnant uptake mechanism that is not measured adequately by current in vitro membrane binding assays. WHHL rabbits possess a normal chylomicron remnant uptake mechanism that allows them to clear chylomicrons from plasma at a rapid rate despite their genetic deficiency of LDL receptors.
منابع مشابه
Chylomicron-remnant clearance in homozygote and heterozygote
Lymph chylomicrons radiolabelled in triacylglycerol and cholesteryl ester were injected into control and Watanabe heritable-hyperlipidaemic (WHHL) rabbits. Clearance of chylomicrons was slower in heterozygote and homozygote WHHL rabbits. Slower remnant clearance in WHHL rabbits was confirmed by monitoring the clearance from plasma of preformed chylomicron remnants. Use of chylomicron-like lipid...
متن کاملConcentration and composition of lipoproteins in blood plasma of the WHHL rabbit. An animal model of human familial hypercholesterolemia.
Lipoproteins in blood plasma have been quantified and characterized in homozygous Watanabe-heritable hyperlipidemic (WHHL) rabbits, an animal model of human familial hypercholesterolemia. Like homozygous human hypercholesterolemics, WHHL rabbits have a severe deficiency of low density lipoprotein (LDL) receptors, a prolonged residence time for LDL, and an increased absolute rate of LDL cataboli...
متن کاملMeasurement of expired carbon dioxide to assess the metabolism of remnant lipoproteins.
The cholesteryl esters transported from the intestine in chylomicrons are delivered to the liver. Hepatocytes take up chylomicron remnants by receptor-mediated endocytosis and the cholesteryl esters are subsequently degraded. In this study we measured the appearance in breath of labeled carbon dioxide after injection of chylomicron-like emulsions labeled with radioactive cholesteryl [1-14C]olea...
متن کاملInfusion of atherogenic lipoprotein particles increases hepatic lipase activity in the rabbit.
Hepatic lipase plays a key role in the turnover of potentially atherogenic lipoprotein remnants and in determining the relative distribution of high density lipoprotein (HDL) particle size subclasses. Rabbits fed a cholesterol-enriched diet have been found to accumulate potentially atherogenic chylomicron remnants and beta-very low density lipoprotein (beta-VLDL) and show a rapid increase in li...
متن کاملPhagocytic degradation of chylomicron remnants by fibroblasts from subjects with homozygous familial hypercholesterolaemia.
1. Familial hypercholesterolaemia is a common genetic abnormality in man characterized by premature atherogenesis as a consequence of disturbed lipoprotein metabolism. Chylomicrons, which represent intestinally derived lipoproteins, are cleared poorly in familial hypercholesterolaemia which may explain the increased retention of chylomicron remnants in arterial fatty lesions. However, cellular ...
متن کاملذخیره در منابع من
با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید
برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید
ثبت ناماگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید
ورودعنوان ژورنال:
- Proceedings of the National Academy of Sciences of the United States of America
دوره 79 11 شماره
صفحات -
تاریخ انتشار 1982