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C Lutton

Publications and source records attributed to C Lutton.

At least 37 records · Page 2Linked to original sources
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↗
PubMed1987

Cholesterol metabolism in the genetically hypercholesterolemic rat (RICO). I. Measurement of turnover processes.

The rates of mobile cholesterol turnover processes were measured by the isotopic equilibrium method in normocholesterolemic (SW) and hypercholesterolemic homozygote (RICO) rats fed a semi-synthetic base diet containing 0.05% cholesterol. When the absorption rate is similar in SW and RICO rats, the internal secretion rate is 60% higher in RICO (25.3 mg/day) than in SW (16.2 mg/day). This increase is compensated by an increase in fecal excretion (RICO: 5 mg/day; SW: 3.8 mg/day), urinary excretion (RICO: 1.7 mg/day; SW: 1.1 mg/day) and above all the transformation of cholesterol into bile acids (RICO: 24.2 mg/day; SW: 15.3 mg/day). The fact that 70 minutes after [14C]acetate administration, the only variations obtained in RICO compared to SW rats are a doubled sterol radioactivity in the small intestine and a tripled one in the liver suggests that the increase in internal secretion of the RICO rat has both an intestinal and hepatic origin. This cholesterogenic stimulation in RICO rats takes place in the jejunum as well as in the ileum and in the crypt cells as well as in the villosities. It is concomitant with a doubled cholesterolemia, a doubled intestinal, caecal and colon bile acid pool and a 20% increase in the enterocyte protein content.

Acetates↗
PubMed1987

Effects of portacaval shunt on the cholesterol metabolism of genetically hypercholesterolemic rats ("Rico' strain).

The effects of portacaval anastomosis on the biodynamics of cholesterol in male adult rats of a genetically hypercholesterolemic strain (Rico) were studied using an isotopic equilibrium method. Animals received a sucrose-rich semipurified diet. In both hypercholesterolemic rats and controls, portacaval anastomosis decreased plasma cholesterol levels (27%), liver weight (35-43%) and total cholesterol content in liver and body pools. Rico rats were characterized by (1) a high input rate of newly synthesized cholesterol (internal secretion) (25.3 +/- 1.9 vs. 16.2 +/- 1.5 mg/day/rat in controls) related to increased hepatic cholesterogenesis, and (2) a high rate of cholesterol transformation into bile acids, while other parameters remained unchanged. Portacaval anastomosis decreased the internal secretion of cholesterol in Rico rats (20.1 +/- 2.0 mg/day/rat). Since the activity of the gut for cholesterol synthesis as shown by the fecal external secretion (cholesterol biosynthesized by the gut and directly eliminated in the gut and feces) was not modified, it is assumed that the reduction of internal secretion induced by portacaval anastomosis results from decreased hepatic cholesterogenesis.

Animals↗
PubMed1986

Evidence for different isotopic enrichments of acetyl-CoA used for cholesterol synthesis in the liver and intestine: a study in the rat by mass fragmentography after intravenous infusion of [13C]acetate.

Wistar rats were killed 4 h after an intravenous infusion of [1,2-13C]- and [1-14C]acetic acid sodium salt (39 mg, 12.5 microCi/ml, constant rate: 1.2 ml/h). At this time, labeled free cholesterol movements between the organs are still weak and cholesterol labeling in each tissue mainly originates from the in situ incorporation of the exogenous substrate. In male rats, the specific radioactivity of free cholesterol was found to be higher in the intestine (mucosa and wall) than in the liver and plasma. In female and in cholestyramine-fed male rats, cholesterol 14C labeling was close to that of male rats in the intestine, and was markedly higher in the liver. The same variations of 13C excess, calculated by mass fragmentography, indicated that there was no isotopic effect between 13C and 14C precursors. The advantage of this method consisted in obtaining the proportions of labeled molecules according to their molecular weight (M + 1-M + 11) for each sample. Then the distribution of 13C atoms in newly synthesized cholesterol was assessed in each sterogenesis site. In the intestine, about 3/4 of the 13C atoms were found in molecules of weight of at least M + 4 (after incorporation of at least two labeled acetate units). This proportion was only 1/3 in hepatic and plasma free cholesterol. These distinct 13C-labeling patterns clearly indicate that local variations occurred in the isotopic enrichment of acetyl-CoA used for cholesterol formation. Whatever the experimental conditions of this study, cholesterol was synthesized from an acetyl-CoA more 13C enriched in the intestine than in the liver. Such variations probably result from the different dilutions of exogenous acetyl-CoA by the endogenous pool in the liver and intestine. Consequently, the 14C or 13C incorporations measured in the liver and intestinal sterols do not account for absolute rates of cholesterol production by these organs. This study also indicated that after a few hours of infusion, free cholesterol labeling in the plasma originated mainly from cholesterol newly formed in the liver, even when acetate incorporation into cholesterol was higher in the intestine than in the liver.

Acetates↗
PubMed1986

In vivo cholesterol synthesis by the rat digestive tract. III. Evaluation of modulating factors.

Sterol radioactivity was measured in the gastrointestinal tract of rats fed a semi-purified basal diet (B), either enriched with 0.5% cholesterol (CH) or containing 2% orotic acid (O). These measurements were taken after a fast of 48 h (CHF) or after fasting and 4-aminopyrazolopyrimidine (APP) treatment (CHFA); the five groups were killed 70 min after a subcutaneous injection of [1-14C]-acetate. Since these results agree with current published data, it is suggested that, although this method is not quantitative, it can give accurate estimates of the qualitative variations of cholesterogenesis in one organ. Adding cholesterol to the diet had no effect on sterogenesis in the stomach and caecum-colon. Fasting for 48 h did not affect cholesterogenesis in the caecum-colon, but stomacal sterogenesis was reduced (50%). APP treatment, which did not affect cholesterogenesis in the stomach, strongly stimulated (4-fold) cholesterogenesis in the caecum-colon. A slight decrease (30%) in intestinal cholesterogenesis was observed after a cholesterol-rich diet. This decrease occurred mainly in villus enterocytes. Fasting reduced cholesterol synthesis 2 to 4-fold mainly in the proximal intestine, while APP treatment stimulated it until a level higher than in nourished control rats. The level of cholesterogenesis was similar in all the enterocytes collected from duodenum to ileum in APP-treated rats. Since there was high mucosa cell loss (about 50%) during the 48-hour APP treatment, total intestinal cholesterogenesis in the CHFA rats was not higher than in the CH animals. Under the present physiological conditions, the feedback inhibition of intestinal cholesterogenesis by luminal bile acids was not clear, while that by luminal cholesterol or by LDL-cholesterol penetrating by specific receptors was modest over a wide range of physiological conditions.

Animals↗
PubMed1985

The effect of lanosterol on platelet aggregation in human platelets.

It has been reported that lanosterol can sensitize isolated rat platelets to agonists such as ADP and thrombin (4). The purpose of this paper was to determine whether lanosterol had similar effects on human platelets and whether this was achieved by changes in membrane fluidity. Lanosterol did increase the sensitivity of human platelets, particularly to adrenaline and ADP at concentrations as low as 5 mg.L-1 when added from solutions in ethanol. At similar concentrations cholesterol, 4-cholesten-3-one or ethynyloestradiol had either no effect or were inhibitory. Measurement of membrane fluidity with diphenylhexatriene indicated that lanosterol did not affect membrane fluidity. Incubation of platelets with [4C]-mevalonic acid gave rise to a very small incorporation into lanosterol, squalene and farnesol. Sudden activation of the platelets did not accelerate lanosterol synthesis during or after platelet aggregation. It was concluded that lanosterol could only influence platelet behaviour if it came from the plasma. However the concentration of the steroid in both platelets and plasma is ten fold less than that required to sensitise the platelets.

Blood Platelets↗
PubMed1985

In vivo cholesterol synthesis by the rat digestive tract. I. A topological study.

Rats were fed a semi-purified diet containing 0.5% cholesterol; cholesterogenesis was measured in vivo 70 min after [1-14C]-acetate or tritiated water was incorporated into the gastrointestinal tract sterols. The results were qualitatively similar with the two precursors. Cholesterol synthesis was preponderant in the small intestine and mainly occurred in its mucosa with a decreasing biosynthetic gradient from the duodenum to the distal ileum. The gradient of cholesterogenesis decreased from the crypt cells to the apical cells in all segments of the intestine studied.

Acetates↗
PubMed1985

In vivo cholesterol synthesis by the rat digestive tract. II. A study of turnover.

In the main organs of the digestive tract of rats fed a semi-purified diet containing 0.5% cholesterol, cholesterol activity was measured 70 min and 8, 24 and 48 h after subcutaneous impulsion of 14C-acetate or intravenous injection of tritiated water. Cholesterol synthesized in the stomach and caecum-colon was not significantly renewed during the 48-hour experiment. On the contrary, cholesterol synthesized in situ in the intestine disappeared with a mean rate constant of 4% X h-1. The rate constant (K) varied (6% X h-1 in the duodenum and jejunum and about 3% X h-1 in the distal ileum) according to the site of the enterocytes in the small intestine. Cell sloughing could not account for the major part of the decrease in cholesterol radioactivity, particularly in the first three quarters of the small intestine. In the proximal half of the gut internal cholesterol secretion via lipoproteins poured into the lymph might play a role.

Acetates↗
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

Cholesterol metabolism in lean and obese Zucker rats: effects of portacaval anastomosis.

The effects of portacaval anastomosis (PCA) on cholesterol biodynamics of male adult (fa/fa) Zucker rats and their lean littermates were studied with an isotopic equilibrium method. Animals were fed with a sucrose-rich semi-purified diet. Obese rats were hypercholesterolemic (2.03 +/- 0.14 vs 1.06 +/- 0.7 mg/ml), had a cholesterol-enriched liver (135.3 +/- 14.5 vs 40.0 +/- 2.6 mg/liver) and accumulated cholesterol in body pools. However no difference in the rates of cholesterol absorption, synthesis, fecal elimination or transformation into bile acids distinguished obese from lean Zucker rats. In both lean and obese rats, PCA decreased cholesterolemia by about 28 per cent and liver weight by 40 per cent while the total cholesterol content of the liver was not affected. Input of synthesized cholesterol (internal secretion) was strikingly decreased by the shunt (from 13.2 +/- 0.6 and 12.6 +/- 0.7 mg/day/rat before PCA, to 8.9 +/- 0.8 and 8.6 +/- 1.0 mg/day/rat after PCA) in lean and obese rats respectively. A similar decrease was observed in the cholesterol transformation into bile acids. Since the activity of the gut for cholesterol synthesis, as shown by the fecal external secretion (cholesterol synthesized by the gut and directly eliminated in the gut and feces) was probably not modified, the reduction of internal secretion induced by PCA resulted from decreased hepatic cholesterogenesis. It is suggested that this decrease may be one of the factors involved in the lowering effect of PCA on plasma cholesterol level.

Animals↗
PubMed1979

Coronary care.

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Coronary Disease↗
PubMed1979

Biliary cholesterol absorption in normal and L-thyroxin-fed rats.

Infusion of bile containing labeled cholesterol into bile fistula rats has permitted an in vivo study of the movements and of the absorption of biliary cholesterol in the digestive tract. The specific activities of cholesterol were similar in the micelles and the sediment of the luminal content after a 6 hr infusion, indicating rapid exchange of cholesterol between these fractions. In animals fed a basal diet, the biliary cholesterol absorption was higher (83%) than that of dietary cholesterol (70%). Bile cholesterol is essentially absorbed in the jejunum while the absorption of cholesterol from the diet takes place all along the small intestine but preferentially in its second and third quarters. Both alimentary cholesterol and bile cholesterol enter the top cells of the villi in preference to those of the crypts. In L-thyroxin-fed rats, a parallel decrease in biliary and dietary cholesterol absorption was observed. The increase in the intestinal transit of cholesterol and epithelium cell renewal of the jejunum accounted for this observation.

Animals↗
PubMed1978

Diet and sterol biohydrogenation in the rat: occurrence of epicoprostanol.

The fecal sterols from rats fed several types of semipurified or commercial diets were analyzed by a combination of thin layer and gas liquid chromatography. In rats fed semipurified diets with lard, sucrose, and casein, increasing proportions of lard (0, 8, 20, 65%) enhanced the fecal coprostanol/coprostanol + cholesterol ratio (from 0.50 to 0.85). This ratio was reduced by replacing lard with triolein or a mixture of calcium oleate and linoleate (1:1) and did not change when trierucin was substituted. No coprostanol formation was observed in rats fed a diet with tripalmitin or tristearin. The addition of sodium hyodeoxycholate (0.5%) or cholestyramine (2%) to the basal diet was without effect on the coprostanol/coprostanol + cholesterol ratio in the feces. The addition of sodium taurocholate (0.2, 0.75, and 4%) strongly reduced coprostanol formation, while a chronic bile duct ligation led to an enhancement. Cholesterol feeding (0.05, 0.2, and 0.5% in the diet) slightly increased (from 51 to 66%) coprostanol formation. Trace amounts of epicoprostanol were generally found in the feces. However, in some cases a very high proportion (up to 60%) of this sterol was observed. Possible relationships between the presence of epicoprostanol and the nature of the diet are discussed.

Animals↗
PubMed1977

Effects of dietary fiber and salt mixtures on the cholesterol metabolism of rats.

The isotopic dilution method, which permits the in vivo measurements of the rates of the processes involved in cholesterol turnover, has been applied to rats fed a commercial stock diet or a basal semipurified diet in which either the nature and proportions of the source of dietary fiber or the salt mixture were changed. The cholesterolemia was about 100 mg/100 g in rats fed agar-agar, cellulose, bran or the stock diet. Pectin addition (5%) lowered significantly the plasma concentration of cholesterol (70 mg/100 g). Changes in the source of dietary fiber or salt mixture have moderate effects on the absorption coefficient of dietary cholesterol (range 58.2%-82%). In comparison to agar-agar, cellulose at 2.3% in the diet significantly lowered this coefficient, but larger amounts of cellulose (6.8% or 12.3%), or pectin (5%) were without effect, while bran addition (10%) tended to slightly decrease cholesterol absorption. Hence, high levels of cellulose in the diet increased the absorption coefficient in comparison to a low cellulose diet. A decrease of this coefficient was also observed when the calcium content of the diet was increased. Cholesterol biosynthesis and fecal excretion were inversely correlated to the absorption coefficient of dietary cholesterol in rats fed all of the semipurified diets indicating, as previously shown, that the intestine was the major source of biosynthesized cholesterol diverted into the plasma. However, feeding a commercial stock diet greatly increased the cholesterogenesis and the fecal elimination of bile acids, suggesting a high hepatic cholesterogenesis.

Animals↗
PubMed1976

[Regulation of cholesterol levels in plasma and liver of adult rats].

The dynamics of cholesterol-system in the plasma is characterized by a parameter which is a linear function of the internal secretion of cholesterol. So, the level of plasma cholesterol from synthesis is a low as its flow is high. Moreover, the level of plasma cholesterol from diet is simultaneously proportional to the flow of cholesterol intestinal absorption and dependent on the dynamics controlled by the internal secretion. The laws of the cholesterolemia cumulate these partial laws. Similar relations concern the esterified cholesterol in the liver.

Animals↗