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.

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.

scholarly journals The lipolysis/esterification cycle of hepatic triacylglycerol. Its role in the secretion of very-low-density lipoprotein and its response to hormones and sulphonylureas

1992 ◽  
Vol 284 (2) ◽  
pp. 457-462 ◽  
Author(s):  
D Wiggins ◽  
G F Gibbons
Keyword(s):  
Fatty Acids ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Very Low Density Lipoprotein ◽  
Low Density ◽  
Intracellular Pool ◽  
Hepatocyte Cultures ◽  
Vldl Secretion ◽  
Vldl Assembly ◽  
Hepatic Triacylglycerol

In hepatocyte cultures maintained in the absence of extracellular fatty acids, at least 70% of the secreted very-low-density lipoprotein (VLDL) triacylglycerol was derived via lipolysis of intracellular triacylglycerol. This proportion was unchanged when the cells were exposed for 24 h to insulin or glucagon, hormones which decreased the overall secretion of intracellular triacylglycerol, or to chloroquine or tolbutamide, agents which inhibit lysosomal lipolysis. The rate of intracellular lipolysis was 2-3-fold greater than that required to maintain the observed rate of triacylglycerol secretion. Most of the fatty acids released were returned to the intracellular pool. Neither insulin nor glucagon had any significant effect on the overall lipolysis and re-esterification of intracellular triacylglycerol. In these cases a greater proportion of the released fatty acids re-entered the cellular pool, rather than being recruited for VLDL assembly. Tolbutamide inhibited intracellular lipolysis, but suppressed VLDL secretion to a greater extent. 3,5-Dimethylpyrazole did not affect lipolysis or VLDL secretion. The increased secretion of VLDL triacylglycerol observed after exposure of cells to insulin for 3 days was not accompanied by an increased rate of intracellular lipolysis. However, a larger proportion of the triacylglycerol secreted under these conditions may not have undergone prior lipolysis.

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 Mitochondrial Glycerol-3-Phosphate Acyltransferase-Deficient Mice Have Reduced Weight and Liver Triacylglycerol Content and Altered Glycerolipid Fatty Acid Composition

2002 ◽  
Vol 22 (23) ◽  
pp. 8204-8214 ◽  
Author(s):  
Linda E. Hammond ◽  
Patricia A. Gallagher ◽  
Shuli Wang ◽  
Sylvia Hiller ◽  
Kimberly D. Kluckman ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Saturated Fatty Acids ◽  
Low Density Lipoprotein ◽  
Fatty Acid Content ◽  
Density Lipoprotein ◽  
Positional Analysis ◽  
Triacylglycerol Content ◽  
Hepatic Triacylglycerol

ABSTRACT Microsomal and mitochondrial isoforms of glycerol-3-phosphate acyltransferase (GPAT; E.C. 2.3.1.15) catalyze the committed step in glycerolipid synthesis. The mitochondrial isoform, mtGPAT, was believed to control the positioning of saturated fatty acids at the sn-1 position of phospholipids, and nutritional, hormonal, and overexpression studies suggested that mtGPAT activity is important for the synthesis of triacylglycerol. To determine whether these purported functions were true, we constructed mice deficient in mtGPAT. mtGPAT−/− mice weighed less than controls and had reduced gonadal fat pad weights and lower hepatic triacylglycerol content, plasma triacylglycerol, and very low density lipoprotein triacylglycerol secretion. As predicted, in mtGPAT−/− liver, the palmitate content was lower in triacylglycerol, phosphatidylcholine, and phosphatidylethanolamine. Positional analysis revealed that mtGPAT−/− liver phosphatidylethanolamine and phosphatidylcholine had about 21% less palmitate in the sn-1 position and 36 and 40%, respectively, more arachidonate in the sn-2 position. These data confirm the important role of mtGPAT in the synthesis of triacylglycerol, in the fatty acid content of triacylglycerol and cholesterol esters, and in the positioning of specific fatty acids, particularly palmitate and arachidonate, in phospholipids. The increase in arachidonate may be functionally significant in terms of eicosanoid production.

Hyperglycemia-induced inhibition of splanchnic fatty acid oxidation increases hepatic triacylglycerol secretion

1998 ◽  
Vol 275 (5) ◽  
pp. E798-E805 ◽  
Author(s):  
Labros S. Sidossis ◽  
Bettina Mittendorfer ◽  
Eric Walser ◽  
David Chinkes ◽  
Robert R. Wolfe
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Fatty Acid Uptake ◽  
Secretion Rate ◽  
Acid Oxidation ◽  
Acid Uptake ◽  
Hepatic Triacylglycerol

The effect of hyperglycemia (∼8 mmol/l) on splanchnic fatty acid oxidation and triacylglycerol (TG) secretion rates was investigated in five healthy men. U-13C-labeled fatty acids were infused to estimate fatty acid kinetics and oxidation across the splanchnic region, and in vivo labeled very low density lipoprotein (VLDL)-TG was infused to estimate TG secretion rate. Plasma fatty acid carbon enrichment and concentration were maintained constant by infusion of lipids and heparin in the hyperglycemia experiments. Fatty acid uptake by the splanchnic region was 1.4 ± 0.2 and 2.2 ± 0.9 μmol ⋅ kg−1⋅ min−1in the basal and clamp experiments, respectively, whereas fatty acid oxidation decreased from 0.4 ± 0.04 to 0.2 ± 0.05 μmol ⋅ kg−1⋅ min−1( P < 0.05). Hepatic TG secretion increased from 0.35 ± 0.07 μmol ⋅ kg−1⋅ min−1in the basal state to 0.53 ± 0.11 μmol ⋅ kg−1⋅ min−1after 15 h of hyperglycemia ( P< 0.05). Similarly, plasma VLDL-TG concentration increased from 0.28 ± 0.06 to 0.43 ± 0.05 mmol/l during the clamp ( P < 0.05). In summary, hyperglycemia attenuates fatty acid oxidation in the splanchnic region in human volunteers, even when fatty acid availability is constant. This adaptation results in a significant increase in the VLDL-TG secretion rate and concentration in plasma.

Comparison of mass isotopomer dilution methods used to compute VLDL production in vivo

1996 ◽  
Vol 271 (2) ◽  
pp. E373-E383 ◽  
Author(s):  
D. L. Chinkes ◽  
A. Aarsland ◽  
J. Rosenblatt ◽  
R. R. Wolfe
Keyword(s):  
Human Subjects ◽  
Low Density Lipoprotein ◽  
Density Lipoprotein ◽  
Difficult Problem ◽  
Theoretical Background ◽  
Data Set ◽  
Isotopomer Distribution ◽  
Fractional Rate ◽  
Mass Isotopomer

The recent development of mass isotopomer distribution methods represents an important new tool for quantifying synthetic rates. These methods allow precursor enrichment to be determined indirectly from the enrichment of the product, thus sidestepping the often difficult problem of measuring the precursor enrichment. Two different methods have been described to compute synthetic rates by this general approach in the laboratories of M. K. Hellerstein and J. K. Kelleher, and variations of these basic approaches have also been presented by W. N. Lee and by ourselves. A comparison between the different methods has never been reported. In this paper, we take a specific application, calculation of the fractional rate of incorporation of acetyl-CoA into very low density lipoprotein-bound palmitate, and compare the results obtained from all of the mass isotopomer methods using the same data set obtained in vivo in human subjects. We found that it is critical that the measured background isotopomer distribution of palmitate is used rather than the theoretical background isotopomer distribution. We also found that the different methods give comparable precursor enrichments and comparable fractional synthesis rates, provided that the enrichments in Kelleher's method are properly weighted. Thus the choice of method to use is a matter of personal preference.

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.

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