scholarly journals Regulation of low-density-lipoprotein metabolism in the rat

1986 ◽  
Vol 234 (2) ◽  
pp. 493-496 ◽  
Author(s):  
S Bhattacharya ◽  
S Balasubramaniam ◽  
L A Simons
Keyword(s):  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hormonal Control ◽  
Low Density ◽  
Experimental Conditions ◽  
Synthetic Rate ◽  
Catabolic Rate ◽  
Intermediate Density

The mechanism of regulation of plasma low-density-lipoprotein (LDL) metabolism in the rat was studied under a number of experimental conditions. LDL clearance and uptake in the liver was measured after intravenous pulse injection of [14C]sucrose-labelled LDL alone or in combination with reductively methylated [3H]sucrose-labelled LDL. Hyperthyroid rats showed a significant increase in fractional catabolic rate (FCR) and the proportion of LDL degraded in the liver, whereas the synthetic rate of LDL increased by 50%. Receptor-mediated clearance increased 2-fold. Hypothyroid rats showed a significant increase in LDL concentration. The FCR and proportion of LDL degraded in the liver were decreased significantly. Receptor-mediated clearance was also reduced. Cholesterol feeding increased chylomicron, very-low-density-and intermediate-density-lipoprotein cholesterol concentrations, but there was no change in the LDL concentration, FCR or the synthetic rate of LDL. Cholestyramine feeding did not induce changes in the kinetic parameters. These results indicate that, in the rat, the hepatic LDL-receptor pathway is under hormonal control, whereas cholesterol and cholestyramine feeding have no demonstrated effect on LDL metabolism.

scholarly journals Effect of Low-Density Lipoprotein Apheresis on Kinetics of Apolipoprotein B in Heterozygous Familial Hypercholesterolemia1

2001 ◽  
Vol 86 (4) ◽  
pp. 1679-1686
Author(s):  
Cyrille Maugeais ◽  
Khadija Ouguerram ◽  
Regis Frénais ◽  
Pascale Maugère ◽  
Bernard Charbonnel ◽  
...  
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Ldl Apheresis ◽  
Catabolic Rate ◽  
High Level

The acute reduction of low-density lipoprotein (LDL) cholesterol obtained by LDL-apheresis allows the role of the high level of circulating LDL on lipoprotein metabolism in heterozygous familial hypercholesterolemia (heterozygous FH) to be addressed. We studied apolipoprotein B (apoB) kinetics in five heterozygous FH patients before and the day after an apheresis treatment using endogenous labeling with [2H3]leucine. Compared with younger control subjects, heterozygous FH patients before apheresis showed a significant decrease in the fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.65 ± 0.22 day−1; P < 0.01), and LDL production was increased in heterozygous FH patients (18.9 ± 7.0 vs. 9.9 ± 4.2 mg/kg·day; P< 0.05). The modeling of postapheresis apoB kinetics was performed using a nonsteady state condition, taking into account the changing pool size of very low density lipoprotein (VLDL), intermediate density lipoprotein, and LDL apoB. The postapheresis kinetic parameters did not show statistical differences compared with preapheresis parameters in heterozygous FH patients; however, a trend for increases in fractional catabolic rate of LDL (0.24 ± 0.08 vs. 0.35± 0.09 day−1; P = 0.067) and the production of VLDL (13.7 ± 8.3 vs. 21.9 ± 1.6 mg/kg·day; P = 0.076) was observed. These results suggested that the marked decrease in plasma LDL obtained a short time after LDL-apheresis is able to stimulate LDL receptor activity and VLDL production in heterozygous FH.

scholarly journals Hypercholesterolemia Due to Lipoprotein X: Case Report and Thematic Review

2019 ◽  
Vol 12 ◽  
pp. 117955141987868 ◽  
Author(s):  
Laura Kattah ◽  
Andrés Gómez ◽  
Sebastián Gutiérrez ◽  
Kathalina Puerto ◽  
Eiman D Moreno-Pallares ◽  
...  
Keyword(s):  
Total Cholesterol ◽  
Low Density Lipoprotein ◽  
Cholesterol Acyltransferase ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Definitive Treatment ◽  
Primary Biliary Cholangitis ◽  
Low Density ◽  
Hepatic Diseases

The liver is a key organ in lipid and lipoprotein metabolism, hence hepatic diseases often manifest as lipid disturbances. Cholestatic liver diseases are frequently associated with an important increase in total cholesterol at the expense of lipoprotein X (LpX), an abnormal lipoprotein isolated and characterized in the 1960s to 1970s in patients with obstructive jaundice. Lipoprotein X is rich in phospholipids, albumin, and free cholesterol, has a density similar to low-density lipoprotein (LDL), and a size similar to very low-density lipoprotein (VLDL), which has hampered its detection through routine laboratory tests. Unlike LDL, LpX has no apoB-100, so it is not removed from circulation via the LDL receptor, and it is not clear whether or not it can be atherogenic. Although LpX was initially described in patients with cholestasis, it has also been found in patients with genetic deficiency of lecithin-cholesterol acyltransferase (LCAT), in patients who receive lipid-rich parenteral nutrition and most recently in patients with graft versus host disease of the liver. In the presence of LpX, plasma total cholesterol can rise up to 1000 mg/dL, which may lead to the development of skin xanthomas and hyperviscosity syndrome. Treatment of LpX-dependent hypercholesterolemia with conventional hypolipidemic drugs is frequently ineffective, and definitive treatment relies on correction of the underlying cause of cholestasis. Here, we present the case of a patient with LpX-dependent hypercholesterolemia in the context of primary biliary cholangitis.

scholarly journals Low-Density Lipoprotein Receptor-Related Proteins in Skeletal Development and Disease

2017 ◽  
Vol 97 (3) ◽  
pp. 1211-1228 ◽  
Author(s):  
Tao Yang ◽  
Bart O. Williams
Keyword(s):  
Skeletal Development ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Protein Family ◽  
Low Density ◽  
Lipoprotein Receptor ◽  
Low Density Lipoprotein Receptor ◽  
Density Lipoprotein Receptor

The identification of the low-density lipoprotein receptor (LDLR) provided a foundation for subsequent studies in lipoprotein metabolism, receptor-mediated endocytosis, and many other fundamental biological functions. The importance of the LDLR led to numerous studies that identified homologous molecules and ultimately resulted in the description of the LDL-receptor superfamily, a group of proteins that contain domains also found in the LDLR. Subsequent studies have revealed that members of the LDLR-related protein family play roles in regulating many aspects of signal transduction. This review is focused on the roles of selected members of this protein family in skeletal development and disease. We present background on the identification of this subgroup of receptors, discuss the phenotypes associated with alterations in their function in human patients and mouse models, and describe the current efforts to therapeutically target these proteins to treat human skeletal disease.

Low density lipoprotein turnover in swine

1978 ◽  
Vol 56 (10) ◽  
pp. 963-967 ◽  
Author(s):  
Y. L. Marcel ◽  
A. C. Nestruck ◽  
M. Bergseth ◽  
M. Bidallier ◽  
W. T. Robinson ◽  
...  
Keyword(s):  
Kinetic Model ◽  
Decay Curve ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Exponential Model ◽  
Low Density ◽  
Miniature Swine ◽  
Synthetic Rate ◽  
Catabolic Rate ◽  
The Mean

The catabolism of intravenously injected 125I-labelled low density lipoproteins (LDL) was followed in normal miniature swine for 2 weeks. When compared with the two-exponential model, the decay curve of the plasma radioactivity associated with the LDL fraction was best described by a three-exponential model. In this system, the half-lives were 4.5 ± 3.7, 19.7 ± 6.6, and 127 ± 70 h (mean of four studies).Assuming a kinetic model with metabolism of LDL in the rapidly equilibrating compartment and two slower equilibrating compartments (a model requiring three exponentials), the mean fractional catabolic rate for apo-LDL was calculated to be 0.015 h−1. Therefore, if at steady state, the synthetic rate for apo-LDL in the same pigs would be 5.6 ± 4.1 mg/h. Different kinetic models using two or three exponentials would provide different value s for the synthetic rate of apo-LDL.However, in view of the known existence of at least three major equilibrating pools for LDL in plasma, liver, and lymph, and in view of the present results, the kinetic model for LDL metabolism should be better represented by a three-exponential system.

scholarly journals Glucagon, cyclic AMP and adrenaline stimulate the degradation of low-density lipoprotein by cultured rat hepatocytes

1989 ◽  
Vol 262 (2) ◽  
pp. 425-429 ◽  
Author(s):  
N F Brown ◽  
A M Salter ◽  
R Fears ◽  
D N Brindley
Keyword(s):  
Cyclic Amp ◽  
Actinomycin D ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Rat Hepatocytes ◽  
Low Density ◽  
Cultured Rat Hepatocytes

Rat hepatocytes were preincubated for 16 h with hormones or drugs and then for a further 8 h with 125I-human low-density lipoprotein (LDL). Glucagon (via cyclic AMP) and adrenaline (via cyclic AMP and alpha-effects) increased the binding of 125I-LDL to the LDL receptor, and the degradation of LDL to [125I]iodotyrosine. The effects on degradation were antagonized by dexamethasone, and the action of cyclic AMP on binding and degradation was inhibited by actinomycin D. The results are discussed in relation to the control of lipoprotein metabolism in diabetes.

scholarly journals Threshold Effects of Circulating Angiopoietin-Like 3 Levels on Plasma Lipoproteins

2017 ◽  
Vol 102 (9) ◽  
pp. 3340-3348 ◽  
Author(s):  
Sergio Fazio ◽  
Jessica Minnier ◽  
Michael D Shapiro ◽  
Sotirios Tsimikas ◽  
Patrizia Tarugi ◽  
...  
Keyword(s):  
Particle Concentration ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Hdl Cholesterol ◽  
Plasma Lipoproteins ◽  
Critical Threshold ◽  
Low Density ◽  
Loss Of Function

Abstract Context Angiopoietin-like 3 (ANGPTL3) deficiency in plasma due to loss-of-function gene mutations results in familial combined hypobetalipoproteinemia type 2 (FHBL2) in homozygotes. However, the lipid phenotype in heterozygotes is much milder and does not appear to relate directly to ANGPTL3 levels. Furthermore, the low-density lipoprotein (LDL) phenotype in carriers of ANGPTL3 mutations is unexplained. Objective To determine whether reduction below a critical threshold in plasma ANGPTL3 levels is a determinant of lipoprotein metabolism in FHBL2, and to determine whether proprotein convertase subtilisin kexin type 9 (PCSK9) is involved in determining low LDL levels in this condition. Design We studied subjects from 19 families with ANGPTL3 mutations and subjects with familial combined hypobetalipoproteinemia type 1 (FHBL1) due to truncated apolipoprotein B (apoB) species. Results First, total cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides, and HDL and LDL particle concentration correlated with plasma ANGPTL3 levels but only when the latter was <25% of normal (<60 ng/dL). Second, the very low-density lipoprotein particle concentration correlated strongly with plasma ANGPTL3 when the latter was <58% of normal. Third, both FHBL1 and FHBL2 subjects showed low levels of mature and LDL-bound PCSK9 and higher levels of its furin-cleaved form. Finally, LDL-bound PCSK9 is protected from cleavage by furin and binds to the LDL receptor more strongly than apoB-free PCSK9. Conclusions Our results suggest that the hypolipidemic effects of ANGPTL3 mutations in FHBL2 are dependent on a threshold of plasma ANGPTL3 levels, with differential effects on various lipoprotein particles. The increased inactivation of PCSK9 by furin in FHBL1 and FHBL2 is likely to cause increased LDL clearance and suggests novel therapeutic avenues.

scholarly journals Interaction of 4-hydroxynonenal-modified low-density lipoproteins with the fibroblast apolipoprotein B/E receptor

1986 ◽  
Vol 234 (1) ◽  
pp. 245-248 ◽  
Author(s):  
W Jessup ◽  
G Jurgens ◽  
J Lang ◽  
H Esterbauer ◽  
R T Dean
Keyword(s):  
Apolipoprotein B ◽  
Negative Charge ◽  
Low Density Lipoprotein ◽  
Ldl Receptor ◽  
Density Lipoprotein ◽  
Low Density ◽  
Lipid Peroxidation Product ◽  
Modified Low Density Lipoproteins ◽  
Peroxidation Product

The incorporation of the lipid peroxidation product 4-hydroxynonenal into low-density lipoprotein (LDL) increases the negative charge of the particle, and decreases its affinity for the fibroblast LDL receptor. It is suggested that this modification may occur in vivo, and might promote atherogenesis.

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