An Appraisal of Methods for Calculating the Fractional Catabolic Rate of Low Density Lipoprotein in Turnover Studies in Humans

1975 ◽  
Vol 49 (3) ◽  
pp. 24P-25P
Author(s):  
G. R. Thompson ◽  
T. Spinks ◽  
A. Ranicar ◽  
N. B. Myant
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Catabolic Rate

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

1997 ◽  
Vol 321 (2) ◽  
pp. 445-450 ◽  
Author(s):  
Miek C. JONG ◽  
Janine H. van REE ◽  
Vivian E. H. DAHLMANS ◽  
Rune R. FRANTS ◽  
Marten H. HOFKER ◽  
...  
Keyword(s):  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Catabolic Rate ◽  
And Control ◽  
Deficient Mice

The function of apolipoprotein (apo) C1 in vivo is not clearly defined. Because transgenic mice overexpressing human apoC1 show elevated triacylglycerol (TG) levels [Simonet, Bucay, Pitas, Lauer and Taylor (1991) J. Biol. Chem. 266, 8651Ő8654], 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)-TG lipolysis, clearance and production, by performing studies with the previously generated apoC1-deficient mice. On a sucrose-rich, low fat/low cholesterol (LFC) diet, apoC1-deficient mice accumulate in their circulation VLDL particles, which contain relatively lower amounts of lipids when compared with VLDL isolated from control mice. Lipolysis assays in vitro on VLDL from apoC1-deficient and control mice showed no differences in apparent Km and Vmax values (0.27ŷ0.06 versus 0.24ŷ0.03 mmol of TG/litre and 0.40ŷ0.03 versus 0.36ŷ0.03 mmol of non-esterified fatty acid (NEFA)/min per litre respectively). To correct for potential differences in the size of the VLDL particles, the resulting Km values were also expressed relative to apoB concentration. Under these conditions apoC1-deficient VLDL displayed a lower, but not significant, Km value when compared with control VLDL (3.44ŷ0.71 versus 4.44ŷ0.52 mmol of TG2/g apoB per litre). VLDL turnover studies with autologous injections of [3H]TG-VLDL in vivo showed that the VLDL fractional catabolic rate (FCR) was decreased by up to 50% in the apoC1-deficient mice when compared with control mice (10.5ŷ3.4 versus 21.0ŷ1.2/h of pool TG). No significant differences between apoC1-deficient and control mice were observed in the hepatic VLDL production estimated by Triton WR139 injections (0.19ŷ0.02 versus 0.21ŷ0.05 mmol/h of TG per kg) and in the extra-hepatic lipolysis of VLDL-TG (4.99ŷ1.62 versus 3.46ŷ1.52/h of pool TG) in vivo. Furthermore, [125I]VLDLŐapoB turnover experiments in vivo also showed a 50% decrease in the FCR of VLDL in apoC1-deficient mice when compared with control mice on the LFC diet (1.1ŷ0.3 versus 2.1ŷ0.1/h of pool apoB). When mice were fed a very high fat/high cholesterol (HFC) diet, the VLDLŐapoB FCR was further decreased in apoC1-deficient mice (0.4ŷ0.1 versus 1.4ŷ0.4/h of pool apoB). We conclude that, in apoC1-deficient mice, the FCR of VLDL is reduced because of impaired uptake of VLDL remnants by hepatic receptors, whereas the production and lipolysis of VLDL-TG is not affected.

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.

Effect of exogenous estrogens on catabolism of VLDL in cholesterol-fed rabbits

1981 ◽  
Vol 241 (5) ◽  
pp. E372-E377
Author(s):  
R. S. Kushwaha ◽  
W. R. Hazzard
Keyword(s):  
Apolipoprotein B ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Pool Size ◽  
Estrogen Treatment ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Catabolic Rate ◽  
Metabolic Mechanism

To determine the metabolic mechanism of the hypolipidemic response to estrogen in cholesterol-fed rabbits, very low-density lipoprotein (VLDL) apolipoprotein B (apoB) turnover studies were conducted in cholesterol-fed animals with or without estrogen treatment. Autologous VLDL apoB had a more rapid fractional catabolic rate (FCR) in estrogen-treated than in untreated animals, but there was no difference in the radioactivity appearing in the intermediate-(IDL) and low- (LDL) density lipoproteins. Similar differences in the FCR were observed when isologous VLDL from donors in the opposite group was injected, suggesting that estrogen treatment in cholesterol-fed rabbits accelerated the catabolism of cholesterol- and apoE-rich lipoproteins by a mechanism that is not dependent on its conversion to LDL. Furthermore, VLDL apoB from normal untreated donor animals was catabolized more rapidly in the estrogen-treated animals, but most of the radioactivity appeared in LDL in both groups. These observations suggest that estrogen treatment of cholesterol-fed rabbits affected only the efficiency but not the completeness of catabolism of normal VLDL. Thus the catabolism of vLDL in cholesterol-fed animals treated with or without estrogen depended on the composition of VLDL injected and the pool size of plasma VLDL, which was reduced by estrogen treatment.

Metabolism of apoprotein B in cynomolgus monkey: evidence for independent production of low-density lipoprotein apoprotein B

1983 ◽  
Vol 244 (2) ◽  
pp. E196-E201
Author(s):  
I. J. Goldberg ◽  
N. A. Le ◽  
H. N. Ginsberg ◽  
J. R. Paterniti ◽  
W. V. Brown
Keyword(s):  
Cynomolgus Monkey ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Low Density Lipoproteins ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Catabolic Rate ◽  
Apoprotein B ◽  
The Mean

The catabolism of very-low-density lipoprotein apoprotein B and its conversion to low-density lipoprotein was studied in five chow-fed cynomolgus monkeys following injection of radioiodinated homologous very-low-density lipoproteins. The mean (+/- SD) fractional catabolic rate of very-low-density lipoprotein apoprotein B was 0.97 +/- 0.20 h-1 and the mean (+/- SD) production rate was 0.76 +/- 0.20 mg X kg-1 X h-1. The percent of conversion of very-low-density lipoprotein apoprotein B to low-density lipoprotein ranged from 33 to 59%. In separate studies of low-density lipoprotein apoprotein B turnover performed using homologous radiolabeled low-density lipoprotein in five additional animals, the mean (+/- SD) fractional catabolic rate for low-density lipoprotein apoprotein B was 0.050 +/- 0.017 h-1 and the mean (+/- SD) apoprotein B production rate was 0.70 +/- 0.18 mg X kg-1 X h-1. Comparison of the total low-density lipoprotein apoprotein B production with that derived from very-low-density lipoprotein apoprotein B suggested that a large fraction of plasma low-density lipoprotein apoprotein B was derived from a source exclusive of circulating very-low-density lipoprotein apoprotein B. This was confirmed in two animals by simultaneous injection of radiolabeled very-low-density and low-density lipoproteins. Thus, a significant proportion of cynomolgus monkey low-density lipoproteins are produced either by direct hepatic secretion or by rapid conversion of lower-density lipoproteins before they appear in the peripheral circulation.

Low-density Lipoprotein Turnover Studies in Man. Evaluation of the Integrated Rate Equations Method, Use of a Whole-body Radioactivity Counter, and the Problem of Partial Denaturation

1979 ◽  
Vol 56 (1) ◽  
pp. 71-76 ◽  
Author(s):  
G. D. Calvert ◽  
H. M. James
Keyword(s):  
Low Density Lipoprotein ◽  
Relative Size ◽  
Density Lipoprotein ◽  
Normal Subjects ◽  
Whole Body ◽  
Rate Equations ◽  
Low Density ◽  
Fractional Catabolic Rate ◽  
Catabolic Rate ◽  
Partial Denaturation

1. We studied the turnover of low-density lipoprotein, density 1·031–1·056 kg/l, in five normal subjects and in four subjects with hyperlipoproteinaemia, using as tracer low-density lipoprotein labelled in the protein moiety with 131I. We analysed data derived with and without a whole-body radioactivity counter. Four models were used, including the integrated rate equations of Nosslin. 2. In most patients all methods gave similar results for the fractional catabolic rate. Use of the integrated rate equations allowed us to calculate the fractional catabolic rate in 3–5 days compared with 12 days for a multicompartmental method using plasma activity alone. The integrated rate equations method was valid only in a steady metabolic state, and could apparently be used when there was minor tracer denaturation. It was probably invalid when there was major partial tracer denaturation. The degree of partial denaturation could be estimated from the whole-body radioactivity graph. The whole-body counter was quick to use, required low levels of radioactivity and avoided error-prone urine collection. 3. Estimates of the relative size of the intravascular and extravascular compartments derived by five different methods were similar in studies in which there was insignificant denaturation of tracer.

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 Galactose-specific asialoglycoprotein receptor is involved in lipoprotein (a) catabolism

2003 ◽  
Vol 376 (3) ◽  
pp. 765-771 ◽  
Author(s):  
Andelko HRZENJAK ◽  
Sasa FRANK ◽  
Xingde WO ◽  
Yonggang ZHOU ◽  
Theo van BERKEL ◽  
...  
Keyword(s):  
Physiological Function ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Asialoglycoprotein Receptor ◽  
Fractional Catabolic Rate ◽  
Wild Type ◽  
Lipoprotein A ◽  
Apolipoprotein A ◽  
Catabolic Rate ◽  
First Time

Lp(a) [lipoprotein (a)] is a highly atherogenic plasma lipoprotein assembled from low-density lipoprotein and the glycoprotein apolipoprotein (a). The rate of Lp(a) biosynthesis correlates significantly with plasma Lp(a) concentrations, whereas the fractional catabolic rate does not have much influence. So far, little is known about Lp(a) catabolism. To study the site and mode of Lp(a) catabolism, native or sialidase-treated Lp(a) was injected into hedgehogs or ASGPR (asialoglycoprotein receptor)-knockout (ASGPR−) mice or wild-type (ASGPR+) mice, and the decay of the plasma Lp(a) concentration was followed. COS-7 cells were transfected with high- (HL-1) and low-molecular-mass ASGPR subunits (HL-2), and binding and degradation of intact or desialylated Lp(a) were measured. In hedgehogs, one of the few species that synthesize Lp(a), most of the Lp(a) was taken up by the liver, followed by kidney and spleen. Lp(a) and asialo-Lp(a) were catabolized with apparent half-lives of 13.8 and 0.55 h respectively. Asialo-orosomucoide increased both half-lives significantly. In mice, the apparent half-life of Lp(a) was 4–6 h. Catabolism of native Lp(a) by wild-type mice was significantly faster compared with ASGPR− mice and there was a significantly greater accumulation of Lp(a) in the liver of ASGPR+ mice compared with ASGPR− mice. The catabolism of asialo-Lp(a) in ASGPR− mice was 8-fold faster when compared with native Lp(a) in wild-type mice. Transfected COS-7 cells expressing functional ASGPR showed approx. 5-fold greater binding and 2-fold faster degradation of native Lp(a) compared with control cells. Our results for the first time demonstrate a physiological function of ASGPR in the catabolism of Lp(a).

Sign in / Sign up

Export Citation Format

Share Document