Nascent and remnant lipoprotein turnover in rats: experimental design and simulation

1983 ◽  
Vol 245 (3) ◽  
pp. R386-R395
Author(s):  
N. Baker ◽  
H. J. Rostami ◽  
J. Elovson
Keyword(s):  
Fatty Acids ◽  
Molecular Weight ◽  
Simulation Analysis ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Kinetic Behavior ◽  
Turnover Rates ◽  
Apoprotein B ◽  
Hydrolysis Of

We have attempted to predict the kinetic behavior of the complex very low-density lipoprotein (VLDL; d less than 1.006) fraction in blood plasma of rats in the steady state. Specifically we proposed a simple model with two different kinds of nascent VLDL particles derived from the liver, one containing apoprotein B (PI/II) [apoB(PI/II)], the high-molecular-weight apoB, and the other, apoprotein B (PIII) [apoB(PIII)], the low-molecular-weight apoB. Two other particles, the corresponding remnants derived from the nascent VLDL particles were also included. Then a number of feasible in vivo tracer experiments were considered in which VLDL labeled in the apoB and/or triglyceride (TG) moieties would be injected into recipient rats and the kinetic behavior of the various compartments predicted by simulation analysis. In addition the kinetic behavior of products such as free fatty acids formed during hydrolysis of labeled TG fatty acids and liver TG derived from labeled circulating remnants was considered. Both the relative sizes of nascent and remnant particles and the extent of average hydrolysis of nascent VLDL-TG (before formation of a remnant particle) were considered in our analysis. On the basis of these predictions we have suggested a number of experimental approaches that should be helpful in defining the relative pool sizes and the turnover rates of each kind of particle in vivo.

scholarly journals The preferential uptake of very-low-density lipoprotein cholesteryl ester by rat liver in vivo

1990 ◽  
Vol 272 (3) ◽  
pp. 735-741 ◽  
Author(s):  
J C Holder ◽  
V A Zammit ◽  
D S Robinson
Keyword(s):  
Fatty Acid ◽  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Apoprotein B ◽  
Preferential Uptake ◽  
Triacylglycerol Fraction

The removal from the blood and the uptake by the liver of injected very-low-density lipoprotein (VLDL) preparations that had been radiolabelled in their apoprotein and cholesteryl ester moieties was studied in lactating rats. Radiolabelled cholesteryl ester was removed from the blood and taken up by the liver more rapidly than sucrose-radiolabelled apoprotein. Near-maximum cholesteryl ester uptake by the liver occurred within 5 min of the injection of the VLDL. At this time, apoprotein B uptake by the liver was only about 25% of the maximum. Maximum uptake of the injected VLDL apoprotein B label was not achieved until at least 15 min after injection, by which time the total uptakes of cholesteryl ester and apoprotein B label were very similar. The results suggest that preferential uptake of the lipoprotein cholesteryl ester by the liver occurred before endocytosis of the entire lipoprotein complex. The fate of the injected VLDL cholesteryl ester after its uptake by the liver was also monitored. Radiolabel associated with the hepatic cholesteryl ester fraction fell steadily from its early maximum level, the rate of fall being faster and more extensive when the fatty acid, rather than the cholesterol, moiety of the ester was labelled. By 30 min after the injection of VLDL containing [3H]cholesteryl ester, over one-third of the injected label was already present as [3H]cholesterol in the liver. When VLDL containing cholesteryl [14C]oleate was injected, a substantial proportion (about 25%) of the injected radiolabelled fatty acid appeared in the hepatic triacylglycerol fraction within 60 min: very little was present in the plasma triacylglycerol fraction at this time.

scholarly journals Quantification in vivo of the effects of different types of dietary fat on the loci of control involved in hepatic triacylglycerol secretion

1995 ◽  
Vol 308 (2) ◽  
pp. 537-542 ◽  
Author(s):  
A M B Moir ◽  
B S Park ◽  
V A Zammit
Keyword(s):  
Fatty Acids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Branch Points ◽  
Pharmacological Agents ◽  
Acid Diet ◽  
Fractional Rate ◽  
Selective Labelling ◽  
Hepatic Triacylglycerol

Polyunsaturated fatty acids (PUFA) have been suggested to exert their hypotriglyceridaemic effect through several possible mechanisms that would be expected to decrease the rate of hepatic very-low-density-lipoprotein-triacylglycerol secretion. We have quantified the role played in vivo by changes in the pattern of partitioning of (i) acyl-CoA between oxidation and esterification, (ii) diacylglycerol between synthesis of triacylglycerol and of the major phospholipids, and (iii) triacylglycerol between secretion and storage within the liver, in response to two dietary levels of n-6 and n-3 PUFA. In order to achieve this we used the technique of selective labelling of hepatic fatty acids in vivo. Compared with a predominantly saturated fatty acid diet, both n-6 and n-3 PUFA intake resulted in a decrease in the proportion of acyl moieties that were secreted by the liver, through an increased diversion of acyl-CoA towards oxidation and a lower fractional rate of secretion of newly synthesized triacylglycerol. In addition, a diet rich in n-3 fatty acids resulted not only in a greater magnitude of these effects but also in a doubling of the partitioning of diacylglycerol towards phospholipid labelling. It is shown that the overall 50% reduction achieved by fish oil feeding in the proportion of acyl groups that were secreted by the liver was distributed over all three branch points. The contribution of each of these adaptations was quantified. The application of such an approach, i.e. the localization and in vivo quantification of the importance of loci of control, in studies on dietary and pharmacological agents that affect lipaemia, is discussed.

Selective inhibitory effects of thyroid hormones on estrogen-induced protein synthesis in chick embryo liver

1985 ◽  
Vol 63 (12) ◽  
pp. 1206-1211 ◽  
Author(s):  
Alex Elbrecht ◽  
Catherine B. Lazier
Keyword(s):  
Thyroid Hormones ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Induced Responses ◽  
Inhibitory Effects ◽  
Apo B ◽  
Apoprotein B ◽  
Nuclear Estrogen Receptor ◽  
Estrogen Stimulation

We have investigated the effect of thyroid hormones on estrogen-induced responses in embryonic chick liver. Administration of thyroid hormones inhibits estrogen induction of vitellogenin, as well as of apoprotein-II of very low density lipoprotein (VLDL apo-II). A proportionate decrease in the concentration of hepatic salt-soluble nuclear estrogen receptor is also observed. In contrast, estrogen stimulation of apoprotein-B (VLDL apo-B) synthesis is relatively resistant to inhibition. The inhibitory effects of the thyroid hormones could be due to increased metabolism and clearance of estradiol-17β in their presence. The relative resistance of estrogen-induced VLDL apo-B synthesis to thyroid hormone inhibition can be explained by its greater sensitivity to low doses of estradiol. In addition, experiments with the antithyroid agent thiourea suggest that, in vivo, estrogen-induced responses could be balanced by the selective inhibitory effects of thyroid hormones.

Comparison of the effects of dietary n−3 and n−6 polyunsaturated fatty acids on very-low-density lipoprotein secretion when delivered to hepatocytes in chylomicron remnants

2001 ◽  
Vol 357 (2) ◽  
pp. 481-487 ◽  
Author(s):  
Xiaozhong ZHENG ◽  
Michael AVELLA ◽  
Kathleen M. BOTHAM
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Fish Oil ◽  
Corn Oil ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Chylomicron Remnants

The effects of chylomicron remnants enriched in n-3 or n-6 polyunsaturated fatty acids (derived from fish or corn oil respectively) on the secretion of very-low-density lipoprotein (VLDL) lipid and apolipoprotein B (apoB) by rat hepatocytes in culture was investigated. Remnants were prepared in vivo from chylomicrons obtained from rats given an oral dose of fish or corn oil and incubated with cultured hepatocytes for up to 16h. The medium was then removed and the secretion of cholesterol and triacylglycerol into the whole medium or the ρ < 1.050g/ml fraction during the following 7–24h was determined. After exposure of the cells to fish-oil as compared with corn-oil remnants, secretion of both cholesterol and triacylglycerol into the whole medium was decreased by 25–35%, and secretion into the ρ < 1.050g/ml fraction was decreased by 20–25%. In addition, the levels of apoB48 found in the ρ < 1.050g/ml fraction were significantly lower in cells treated with fish-oil rather than corn-oil remnants, although the levels of apoB100 remained unchanged. The expression of mRNA for apoB, as determined by reverse-transcriptase PCR, however, was not significantly changed after exposure of the cells to both types of remnants. These results demonstrate that the effects of dietary n-3 polyunsaturated fatty acids in depressing hepatic VLDL secretion occur directly when they are delivered to the liver from the intestine in chylomicron remnants, and that the secretion, but not the synthesis, of apoB is targeted.

scholarly journals Secretion and storage of newly synthesized hepatic triacylglycerol fatty acids in vivo in different nutritional states and in diabetes

1988 ◽  
Vol 255 (3) ◽  
pp. 929-935 ◽  
Author(s):  
J M Duerden ◽  
G F Gibbons
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Diurnal Variation ◽  
Low Density Lipoprotein ◽  
Specific Radioactivity ◽  
Lipid Synthesis ◽  
Density Lipoprotein ◽  
Dark Phase ◽  
Light Phase

Hepatic lipid synthesis was measured in rats in vivo with 3H2O, and the appearance of label in triacylglycerol and its constituent fatty acid and glycerol moieties was determined. In rats treated with Triton WR1339, the amount of newly synthesized fatty acid secreted as very-low-density lipoprotein (VLDL) triacylglycerol was greater during the dark phase of the diurnal cycle than during the light phase (11.3 versus 4.8 mumol of 3H2O/3 h per g of liver respectively). However, the total mass of VLDL triacylglycerol secreted remained constant, as did the amount of label in the secreted triacylglycerol glycerol. Newly synthesized fatty acids comprised only a small proportion of the total VLDL triacylglycerol fatty acids (TGFA) at both times (dark phase, 7.7%; light phase, 2.4%). Starvation for 24 h resulted in a small increase in the secretion of VLDL triacylglycerol. However, the contribution from newly synthesized fatty acids was decreased. Similar effects were observed in streptozotocin-diabetic animals. During the light and dark phases of the cycle, similar quantities of newly synthesized TGFA entered the hepatic cytosol, and these amounts were much smaller than those secreted as VLDL triacylglycerol. The mass of cytosolic triacylglycerol showed a diurnal variation, with a greater concentration during the light phase than in the dark. In diabetes, the mass of triacylglycerol was increased in the cytosol, as was the incorporation of labelled acylglycerol glycerol. Diabetes also abolished the diurnal variation in the quantity of cytosolic triacylglycerol. In each group of animals the specific radioactivity of the microsomal triacylglycerol was similar to that of the respective newly secreted plasma VLDL. The specific radioactivity of the cytosolic triacylglycerol was only 15.8% (dark phase) or 16.8% (light phase) that of the microsomal triacylglycerol. This increased to 35.5% in the starved animals and 40.2% in the diabetic animals.

scholarly journals Differences in partitioning of meal fatty acids into blood lipid fractions: a comparison of linoleate, oleate, and palmitate

2009 ◽  
Vol 296 (1) ◽  
pp. E64-E71 ◽  
Author(s):  
Leanne Hodson ◽  
Siobhán E. McQuaid ◽  
Fredrik Karpe ◽  
Keith N. Frayn ◽  
Barbara A. Fielding
Keyword(s):  
Fatty Acids ◽  
Test Meal ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Blood Lipid ◽  
Nonesterified Fatty Acid ◽  
Lipid Fractions ◽  
Functional Consequences ◽  
Single Meal

There has been much interest in the health effects of dietary fat, but few studies have comprehensively compared the acute metabolic fate of specific fatty acids in vivo. We hypothesized that different classes of fatty acids would be variably partitioned in metabolic pathways and that this would become evident over 24 h. We traced the fate of fatty acids using equal amounts of [U-13C]linoleate, [U-13C]oleate, and [U-13C]palmitate given in a test breakfast meal in 12 healthy subjects. There was a tendency for differences in the concentrations of the tracers in plasma chylomicron-triacylglycerol (TG) (oleate > palmitate > linoleate). This pattern remained in plasma nonesterified fatty acid (NEFA) and very low-density lipoprotein (VLDL)-TG ( P ≤ 0.01 and P ≤ 0.02 for [U-13C]oleate vs. both [U-13C]palmitate and [U-13C]linoleate for NEFA and VLDL-TG, respectively). There was significantly more [U-13C]linoleate than the other two tracers in plasma cholesteryl ester and phospholipid (PL). Using the values for isotopic enrichment in the different lipid fractions compared with the test meal, we calculated the contribution of meal fatty acids to the respective fractions. At 24 h, 10% of plasma PL-linoleate originated from the breakfast test meal. This was significantly greater than for oleate and palmitate (both 3 ± 0.3%; P < 0.05). This pattern was also true for erythrocyte PL fatty acids. The marked rapid incorporation of linoleate from a single meal into blood PL fractions may have functional consequences such as maintenance of membrane fluidity and may explain why linoleate is a useful biomarker of dietary intake.

scholarly journals No effect of 10 weeks erythropoietin treatment on lipid oxidation in healthy men

2020 ◽  
Vol 9 (12) ◽  
pp. 1148-1155
Author(s):  
Jeyanthini Risikesan ◽  
Birgitte Nellemann ◽  
Britt Christensen ◽  
Jens Otto Lunde Jørgensen ◽  
Søren Nielsen
Keyword(s):  
Fatty Acids ◽  
Lipid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Resting Energy Expenditure ◽  
Oxidation Rates ◽  
Relative Contribution ◽  
The Impact

Studies indicate that erythropoietin (EPO) has effect on lipid and energy metabolism; however, the impact of EPO on lipid oxidation in vivo has not been well documented. Here, we evaluate whether long-term erythropoiesis-stimulating agent (ESA) treatment affects the oxidation of plasma very low-density lipoprotein triglycerides (VLDL-TG) fatty acids (FA), plasma free fatty acids (FFA) and non-plasma (residual) FA in healthy, young, sedentary men. Infusion of [1-14C]VLDL-TG and [9,10-3H]palmitate was used in combination with indirect calorimetry to assess resting lipid fuel utilization and kinetics, and resting energy expenditure (REE) before and after 10 weeks of ESA exposure compared with placebo. REE increased significantly during ESA compared with placebo (P = 0.023, RM-ANOVA). Oxidation rates of VLDL-TG FA, FFA, and residual FA remained unchanged during ESA compared with placebo. The relative contribution of the lipid stores was greatest for FFA (47.1%) and the total lipid oxidation rate and was not significantly different between ESA and placebo-treated subjects. We conclude that long-term ESA treatment of healthy young men increases REE but does not alter the oxidation rates of plasma and non-plasma FA sources.

scholarly journals Effects of an oral and intravenous fat load on adipose tissue and forearm lipid metabolism

1999 ◽  
Vol 276 (2) ◽  
pp. E241-E248 ◽  
Author(s):  
Kevin Evans ◽  
Mo L. Clark ◽  
Keith N. Frayn
Keyword(s):  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Subcutaneous Adipose

We have studied the fate of lipoprotein lipase (LPL)-derived fatty acids by measuring arteriovenous differences across subcutaneous adipose tissue and skeletal muscle in vivo. Six subjects were fasted overnight and were then given 40 g of triacylglycerol either orally or as an intravenous infusion over 4 h. Intracellular lipolysis (hormone-sensitive lipase action; HSL) was suppressed after both oral and intravenous fat loads ( P < 0.001). Insulin, a major regulator of HSL activity, showed little change after either oral or intravenous fat load, suggesting that suppression of HSL action occurred independently of insulin. The rate of action of LPL (measured as triacylglycerol extraction) increased with both oral and intravenous fat loads in adipose tissue ( P = 0.002) and skeletal muscle ( P = 0.001). There was increased escape of LPL-derived fatty acids into the circulation from adipose tissue, shown by lack of reesterification of fatty acids. There was no release into the circulation of LPL-derived fatty acids from skeletal muscle. These results suggest that insulin is not essential for HSL suppression or increased triacylglycerol clearance but is important in reesterification of fatty acids in adipose tissue but not uptake by skeletal muscle, thus affecting fatty acid partitioning between adipose tissue and the circulation, postprandial nonesterified fatty acid concentrations, and hepatic very low density lipoprotein secretion.

scholarly journals Selective labelling of hepatic fatty acids in vivo. Studies on the synthesis and secretion of glycerolipids in the rat

1992 ◽  
Vol 283 (1) ◽  
pp. 145-149 ◽  
Author(s):  
A M B Moir ◽  
V A Zammit
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Cholesteryl Ester ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Streptozotocin Diabetes ◽  
In Vivo Studies ◽  
Selective Labelling ◽  
Glycerolipid Synthesis

1. We describe a method for the selective labelling of hepatic fatty acids in the rat in vivo. It relies on (i) the rapid and preferential uptake of cholesteryl ester from chylomicron and/or very-low-density-lipoprotein remnants by the liver [Holder, Zammit & Robinson (1990) Biochem. J. 272, 735-741] (without prior exchange of the ester to other lipoproteins in the plasma), and (ii) the very short half-life of the cholesteryl ester in the liver. The 14C-labelled fatty acid moiety generated by cholesteryl ester hydrolysis was shown to be utilized by the liver for glycerolipid synthesis in a very similar pattern to that demonstrated for exogenous fatty acids by isolated cultured hepatocytes in previous studies. 2. Starvation (24 h) was shown to decrease the proportion of fatty acid utilized for glycerolipid synthesis, but to result in a proportionately smaller effect on incorporation into phospholipid. This was accompanied by a decrease in the fraction of synthesized triacylglycerol that was secreted by the liver. 3. Streptozotocin-diabetes did not affect the phospholipid/triacylglycerol ratio, but resulted in a small, but significant, decline in the fraction of triacylglycerol secreted by the liver. 4. In both starved and diabetic animals fatty acid esterification to the glycerol moiety constituted a smaller proportion of the total disposal of label. 5. These findings appear to validate the present method for the selective labelling of liver fatty acids in vivo in a non-invasive manner. Other possible uses for the method are suggested.

Adipose tissue sensitization to insulin induced by troglitazone and MEDICA 16 in obese Zucker rats in vivo

2003 ◽  
Vol 284 (4) ◽  
pp. E795-E803 ◽  
Author(s):  
Bella Kalderon ◽  
Nina Mayorek ◽  
Limor Ben-Yaacov ◽  
Jacob Bar-Tana
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Constant Infusion ◽  
Zucker Rats ◽  
Fasting State ◽  
Insulin Sensitizers ◽  
Adipose Tissue Lipolysis

The putative role played by insulin sensitizers in modulating adipose tissue lipolysis in the fasting state was evaluated in obese conscious Zucker rats treated with troglitazone or β,β′-tetramethylhexadecanedioic acid (MEDICA 16) and compared with nontreated lean and obese animals. The rates of appearance (Ra) of glycerol and free fatty acid (FFA), primary intra-adipose reesterification, and secondary reuptake of plasma FFA in adipose fat were measured using constant infusion of stable isotope-labeled [2H5]glycerol, [2,2-2H2]palmitate, and radioactive [3H]palmitate. The overall lipolytic flux (Raglycerol) was increased 1.7- and 1.4-fold in obese animals treated with troglitazone or MEDICA 16, respectively, resulting in increased FFA export (Ra FFA) in the troglitazone-treated rats. Primary intra-adipose reesterification of lipolysis-derived fatty acids was enhanced twofold by insulin sensitizers, whereas reesterification of plasma fatty acids was unaffected by either treatment. Despite the unchanged Ra FFA in MEDICA 16 or the increased Ra FFA induced by troglitazone, very low density lipoprotein production rates were robustly curtailed. Total adipose tissue reesterification, used as an estimate of glucose conversion to glyceride-glycerol, was increased 1.9-fold by treatment with the insulin sensitizers. Our results indicate that, in the fasting state, insulin sensitizers induce, in vivo, a significant activation rather than suppression of adipose tissue lipolysis together with stimulation of glucose conversion to glyceride-glycerol.

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