PubMed Health⌕ Search

Biomedical subjects

T Magot

Publications and source records attributed to T Magot.

At least 19 recordsLinked to original sources
PubMed1992

Metabolism of intestinal triglyceride-rich lipoproteins in the genetically hypercholesterolemic rat (RICO)

Experiments were carried out to compare the catabolism of intestinal lipoproteins between genetically hypercholesterolemic (RICO) and normocholesterolemic (SW) rats. Kinetics of plasma cholesteryl ester were studied after injection of cholesterol-labeled chylomicrons or VLDL. The chylomicron clearance is reduced in the RICO rat (rate constant, K = 7.2 +/- 0.1 h-1 vs. 10.7 +/- 0.1 h-1 in SW rat), while a much more minor alteration was observed in the catabolism of lymph VLDL (K = 4.3 +/- 0.6 h-1 in the RICO rat vs. 5.1 +/- 0.4 h-1). The injection of chylomicrons from SW rats to RICO rats and from RICO rats to SW rats showed that the fall in the rate of catabolism of chylomicrons in RICO rats was not secondary to an increase in the production rate, but was related to the lipoprotein particle itself without any alteration of the catabolic system. The reduction in the rate of catabolism of chylomicrons in the RICO rat could be related to a change in their apolipoprotein composition (increase in the proportion of apolipoprotein E = 12 +/- 2% vs. 3 +/- 1% in the SW rat).

Animals↗
PubMed1992

Overestimation of the lipoprotein fractional catabolic rate (FCR) measured in short duration experiments.

The aim of the study was to compare two methods classically used in rats to determine the fractional catabolic rate (FCR) of labeled high or low density lipoproteins: constant infusion and single pulse. The FC of [14C]-sucrose HDL (High density lipoprotein) was studied. For the short term experiment (8 hours), both methods gave similar FCR determined 8 hours after HDL constant infusion (9.4%.h-1 +/- 0.6) or single pulse (8.5%.h-1 +/- 0.4), values significantly higher than those measured 24 hr after the single pulse (6.2%.h-1 +/- 0.3). The identification and simulation of the model representing HDL movements between an intravascular and extravascular pool, after single pulse and constant infusion methods, demonstrated that FCR of lipoproteins cannot be precisely measured with techniques involving excessively short observation periods.

Animals↗
PubMed1991

In vivo effect of simvastatin on lipoprotein cholesteryl ester metabolism in normocholesterolemic volunteers.

A kinetic study on lipoprotein cholesteryl ester metabolism was carried out in 4 normolipidemic volunteers before and after treatment with simvastatin. They received LDL labelled with 3H-cholesteryl linoleate. A lipoprotein cholesteryl ester model was developed that fit the radioactivity in LDL, HDL and VLDL cholesteryl ester during 24 hours following injection. Before treatment, the model is consistent with previously reported data. Moreover our results suggest that, in normal fasting subjects, the efflux of plasma cholesteryl ester is almost exclusively derived from LDL. Administration of drug decreased LDL cholesteryl ester concentration by 35%. After treatment, the rate constant concerning LDL catabolism was increased by 25% and the model required the existence of a direct removal of VLDL cholesteryl ester (40% of total VLDL turnover). Our results suggest that the reduction in the LDL cholesteryl ester concentration induced by treatment with simvastatin is due to an increase in the uptake of LDL and LDL precursors (VLDL, VLDL remnants) by LDL receptors.

Adult↗
PubMed1990

Critical analysis of the use of 14C-acetate for measuring in vivo rat cholesterol synthesis.

The bulk of cholesterol produced by the liver and the gut enters the mobile pool of body cholesterol. This process is called internal secretion in contrast with the fraction of biosynthesized cholesterol directly eliminated in the feces (fecal external secretion). In rats, under various conditions, a linear relationship was found between the rates of internal secretion measured by the isotope equilibrium method (range: 10-60 mg/day) and the sum of sterol radioactivities measured in liver and intestine 70 min after a [14C]-acetate pulse. In fact, a better correlation was found between the radioactivities of liver sterols and the values for internal secretion. In this new relationship, the ordinate at the origin corresponds to a minimal internal secretion of about 10 mg/day, which implies an important extrahepatic cholesterol production, probably from the gut. Indeed, in adult male rats, fed a semi-purified sucrose-rich diet, the relative contribution of this organ to the internal secretion was higher than in adult rats fed a commercial diet and higher than in young animals, whatever the circadian period. It can be concluded that some of the discrepancies observed in the literature about the relative participation of the intestine and the liver in the internal secretion of cholesterol are probably due to differences in experimental and nutritional conditions (age and sex of the animals, diet composition, time of the circadian cycle) rather than to the cholesterol precursor used (3H2O or [14C] acetate) to assess the activity of cholesterol synthesis. Indeed, a comparative study of 3H2O and [14C]acetate incorporation into sterols of enterocytes indicated the same crypt-villus radioactive gradient, regardless of the intestinal site studied (duodenum, jejunum or ileum) and thus validated the use of [14C]acetate. Other experiments however, showed evidence of some local differences in the cytosolic dilution of labeled acetyl CoA by the endogenous cholesterol precursor in rats under various conditions (control or cholestyramine-enriched diet, parenteral nutrition). After intravenous infusion of 1,2[13C]acetate, mass fragmentography of free cholesterol isolated from liver and intestine indicated different 13C-labeling patterns of newly synthesized molecules. They indicate that cholesterol is generally synthesized from acetyl CoA with a lower 13C-content in the liver than in the intestine. The local endogenous flow of acetyl CoA used for cholesterol synthesis was about 2-fold higher in the hepatocytes than in the enterocytes. This conclusion was confirmed by the results obtained with several experimental groups exhibiting a large range of both internal secretion of cholesterol and sterol radioactivities in liver and intestine after [14C]acetate injection.(ABSTRACT TRUNCATED AT 400 WORDS)

Acetates↗
PubMed1990

Turnover of [14C] sucrose HDL and uptake by organs in the normal or genetically hypercholesterolemic (RICO) rat using a constant infusion method.

The turnover and tissular uptake of HDL (d 1.095-1.21) have been compared in normocholesterolemic or genetically hypercholesterolemic rats by a constant infusion method of [14C] sucrose labelled HDL for 8 h. The HDL clearance rate was not significantly smaller in the RICO than in the normocholesterolemic animal (320 +/- 22 microliters.h-1 versus 366 +/- 24 microliters.h-1 per 100 g of rat). It was the same case for the fractional catabolic rate, respectively equal to 7.8 and 9.4 +/- 0.6%.h-1. For both strains, liver and skeletal muscle were the main catabolic sites for HDL. The HDL uptake rates in intestine or kidney were 3-4-fold smaller than those in the liver. In the RICO rat, intestine, testis and adrenals showed a lesser HDL uptake capacity (expressed per g of organ) than the normocholesterolemic rat.

Animals↗
PubMed1989

Effect of simvastatin on receptor-dependent low density lipoprotein catabolism in normocholesterolemic human volunteers.

Simvastatin, an inhibitor of HMG-CoA reductase was given to 7 normolipidemic healthy volunteers for 1 month at a dose of 20 mg/day. Measurements of turnover of low density lipoprotein apolipoprotein B (LDL-apo B) were determined before and after drug treatment using intravenous injection of 125I-labeled LDL and 131I-labeled cyclohexanedione-treated LDL to quantify the receptor pathway. In addition to a 13% increase in HDL cholesterol and apolipoprotein A-I concentrations, plasma cholesterol was reduced by 20%, LDL-cholesterol by 32%, and apolipoprotein B by 23%. Assuming a heterogeneous pool of LDL, the new model presented in the companion paper was built to calculate the contribution of the receptor-dependent and the receptor-independent pathways and the corresponding fractional catabolic rates. Simvastatin did not modify constantly the synthetic rate of LDL-apo B but increased the fractional catabolic rate of the receptor-dependent pathway and the contribution of this pathway in the catabolism. The fall in LDL plasma levels observed in normocholesterolemic subjects can be then entirely explained by an enhanced fractional removal of LDL from the circulation by the receptor route.

Adult↗
PubMed1989

Apolipoproteins C-II and C-III metabolism in hypertriglyceridemic patients. Effect of a drastic triglyceride reduction by combined diet restriction and fenofibrate administration.

Four hypertriglyceridemic patients, who had received an equilibrated high calorie diet and no lipid lowering drug for 1 month, were injected intravenously with 125I-apo C-II and 131I-apo C-III labeled homologous lipoproteins. Plasma and urine radioactivity, lipid and apolipoprotein levels were followed at regular intervals for 15 days. At the end of this first kinetic study the patients were advised to adhere for 1 month to a more restricted diet, limited in fat, and were given additionally 300 mg fenofibrate daily. After this treatment, a new kinetic study involving intravenous injection (similar to the first one) was performed. The protocols of both studies were identical. Treatment (diet plus drug) (1) reduced total cholesterol by 26 +/- 8%, triglycerides by 56 +/- 15%, apo C-II by 36 +/- 14%, and apo C-III by 48 +/- 10%; (2) modified the distribution of radioactivity between lipoproteins proportionally to the change in their mass ratio (decrease in VLDL and increase in HDL); (3) changed the kinetics of both apoproteins by rising the fractional removal rate, shortening residence time and decreasing the synthesis rate of both apolipoproteins C-II and C-III. The treatment was, however, unable to reduce the synthesis rate of apo C-III to normal, suggesting a major role of the apoprotein overproduction in the triggering of hypertriglyceridemia.

Apolipoproteins C↗
PubMed1987

Origin and fate of rat plasma cholesterol in vivo. Modelling of cholesterol movements between plasma and organs.

A cholesterol system model was developed in the rat following a single injection of red cells containing free (unesterified) [3H]cholesterol. The radioactivity of free and esterified cholesterol in the different parts of the system was measured during the 48 h following tracer introduction. The model consisted of seven compartments (red cell free cholesterol, plasma and liver free and esterified cholesterol, total cholesterol in the rapidly and slowly exchangeable carcass pools). The model was validated by the similarity between simulated and experimental values during the 48 h following tracer introduction. Both the fractional rate of cholesterol esterification in the plasma (0.44 h-1) and liver (0.01 h-1) and the fractional exchange rate of free cholesterol from the plasma towards the various organs (particularly 3 h-1 towards the liver for a total of 7 h-1) can be estimated with this model. The results show that cholesterol movements between the plasma and the different organs take place mainly through intense free cholesterol exchanges, resulting in a low net flux.

Animals↗
PubMed1985

The measurement in vivo of the rate of unesterified cholesterol exchange between rat plasma and erythrocytes.

In order to investigate the rate of unesterified cholesterol exchange between plasma and erythrocytes in vivo, cholesterol labelling in rats was achieved in one of the following ways: intravenous injection of cholesterol-labelled erythrocytes, subcutaneous injection of labelled acetate, feeding of labelled cholesterol. The specific activity of the unesterified cholesterol was measured at intervals up to 24 h and a kinetic analysis of the data was performed. It assumes that both the cholesterol in the erythrocytes and the unesterified cholesterol in the plasma were homogeneous pools. The rate constants obtained for the movements of unesterified cholesterol from erythrocytes to plasma and from plasma to erythrocytes were not significantly different in the three labelling conditions (mean values: 0.26 and 1.5 h-1, respectively).

Animals↗
PubMed1985

Development of a program package for modelling biochemical systems.

The development of a program for the identification of a model including up to 15 compartments is presented. The identification of the model parameters with this program package is based upon the improved Gauss Marquardt algorithm. This program, implemented on a microcomputer (Data General Eclipse 64 K RAM), uses a calculation and automatic generation of a partial derivative routine. Thus, starting from the differential equations of the model correctly written, there is no longer any risk of error.

Animals↗
PubMed1985

Origin and fate of cholesterol in rat plasma lipoproteins in vivo. I. Qualitative analysis.

Rats were conditioned to ingest a 15-gram dietary mixture, in a single daily meal, between 6:00 and 9:00 a.m. Labeled cholesterol was introduced into the organism through four different physiological routes: ingestion of 14C-cholesterol, injection of 14C-acetate, injection of red cells or plasma whose cholesterol was tritium-labeled. The specific radioactivities of free and esterified cholesterol, in the different plasma lipoproteins and in the major organs, were measured at various time spans after the introduction. The results revealed a different source of cholesterol in chylomicrons and VLDL discharged by the intestine: the chylomicrons would principally carry esterified cholesterol coming from the intestinal contents, while esterified cholesterol coming from the intestinal wall was found mainly in VLDL. The free cholesterol of these lipoproteins would initially have the same origin as esterified cholesterol but rapid free cholesterol exchanges would introduce precociously cholesterol coming from other structures. The results demonstrated the significant role of the intestine in cholesterol synthesis and revealed that of VLDL in the internal secretion of cholesterol by the intestine. Chylomicrons also appeared to play a significant role in this secretion, by way of exchanges between intestinal cells and chylomicrons in the process of formation. Finally, the results suggested the existence of esterified cholesterol transfers from HDL to lower density lipoproteins (chylomicrons, VLDL and possibly LDL).

Animals↗
PubMed1985

Origin and fate of cholesterol in rat plasma lipoproteins in vivo. II. Modelling of cholesterol absorption and its release into plasma lipoproteins.

After a single ingestion of a diet containing 14C-cholesterol, cholesterol radioactivity in the stomachal and intestinal contents, in the different organs and in the very low density lipoproteins (VLDL) and chylomicrons was measured at different times during 2 days. Based on the results, a quantitative model of cholesterol absorption and of its release into the VLDL and chylomicrons has been elaborated. This model takes into account the different processes implied in the turnover of intestinal cholesterol and that of the entire organism. It constitutes a coherent whole (satisfactory simulations for the variables studied, suitable mass balances for each compartment and the absence of major contradictions with preexisting quantitative data). Once again the model demonstrates the important part played by the intestine in rat cholesterol system dynamics. It takes into account the existence of two related exogenous and endogenous cholesterol pools from which the cholesterol released by the intestine into the chylomicrons and VLDL originates. The results suggest the existence of an important esterified cholesterol uptake from other plasma lipoproteins by the chylomicrons.

Animals↗
PubMed1985

[Origin and fate of cholesterol in rat plasma lipoproteins in vivo. III. Demonstration and measurement of the flow rate of HDL esterified cholesterol to the chylomicrons].

A study has been carried out to measure the transfer rate of esterified cholesterol from the HDL into the chylomicrons, as previously suggested. Rats were intravenously injected with cholesterol-labelled plasma or red cells. The specific activity of esterified cholesterol of HDL and chylomicrons was measured during 12 h following injection. Results were treated by compartmental analysis. The transfer rate was 0.21-0.22 h-1 with an uptake rate of chylomicrons by the liver of 8 h-1 (t1/2 5 min). This represents a 0.8 mg h-1 flux of esterified cholesterol from HDL into chylomicrons, i.e., in our conditions, 75% of the total input into the chylomicrons esterified cholesterol. This process could be the major way for the disappearance of HDL esterified cholesterol.

Animals↗
PubMed1976

In vivo study of free and esterified cholesterol turnover in various tissues of the rat.

Rats were infused for 3.5 to 10 hrs with either red cells or plasma previously labelled in vivo by [3H]-cholesterol. Cholesterol specific radioactivities were measured in plasma, HDL, LDL and VLDL, and various tissues. Red cell infusions led to a higher labelling of free than of esterified cholesterol in the plasma of infused rats. The opposite situation was observed following plasma infusion. Comparison of free and esterified cholesterol specific radioactivities in each tissue showed that esterified cholesterol was transferred from plasma to all the tissues, except the adrenals. Study of the ratios of cholesterol specific radioactivities from one experimental group to the other in each tissue, made it possible to demonstrate clearly the occurence of hydrolysis within all the studied tissues except 5 of them where its existence remains uncertain (lung, heart, kidney, tendon, muscle) and of esterification in 3 tissues (adrenal, liver lung). In addition, ratios of cholesterol radioactivities (free/ester) were found to be identical in plasma and in 4 tissues, where neither hydrolysis nor esterification were detected (heart, muscle, kidney, tendon). This finding is an argument in favor of a simultaneous transport of free and esterified cholesterol from plasma into these 4 tissues and suggests that the entire lipoprotein particles can penetrate these tissues, with no specificity of one special class. In adrenal, unlike all other tissues: 1) the turnover of esterified cholesterol was achieved mostly by hydrolysis and esterification in situ; 2) a preferential lipoprotein class (LDL) was responsible for the transport of free cholesterol from the plasma.

Adrenal Glands↗