Total Plasma Free Fatty Acid Research Articles

Coordination of very low-density lipoprotein triglyceride and apolipoprotein B metabolism in humans: Effects of obesity and non-insulin-dependent diabetes mellitus

To understand the relationship between very low-density lipoprotein (VLDL) triglyceride and VLDL apolipoprotein (apo) B, we studied their metabolisms simultaneously in 53 subjects with a range of obesity and glycemia. Obese subjects had increased production of both VLDL apo B and VLDL triglyceride and more VLDL of normal composition. Compared with nondiabetics, diabetic subjects had decreased clearance of both VLDL apo B and VLDL triglyceride, increased production of VLDL triglyceride but not of VLDL apo B, and more VLDL of abnormal composition. Production of both VLDL apo B and VLDL triglyceride were significantly correlated with plasma insulin concentrations, and rates of clearance of both were inversely correlated with plasma glucose. There was no direct correlation between total plasma free fatty acid concentration and production of either VLDL triglyceride or VLDL apo B, but VLDL triglyceride production was found to account for only a very small proportion of the nonoxidative component of free fatty acid turnover. We suggest that in obese subjects hyperinsulinemia induces overproduction of both VLDL apo B and VLDL triglyceride. In diabetes VLDL is increased in part because of decreased clearance; the altered composition is the result of the increase in VLDL-triglyceride production independent of apo B. The increase in VLDL triglyceride production may be mediated through plasma free fatty acids or glucose, although assessment of the relationship between these precursors and VLDL triglyceride is confounded by the fact that only a small portion of free fatty acids or glucose is converted to VLDL triglyceride.

The effect of systemic heparinisation and haemodialysis on plasma octadeca-9,11-dienoic acid (9,11-LA').

Systemic heparinisation induces a sharp rise not only in plasma total free fatty acids but also in 9,11-LA' concentration and in the 9,11-LA'/9,12-LA molar ratio. This "heparin effect" is enhanced by haemodialysis with cuprophan membranes but not with polycarbonate membranes.

トレーニングが血中及び脂肪組織の脂肪酸構成比にあたえる影響

The purpose of the present study was to investigate the influence of training on the metabolism of plasma free fatty acid (FFA), and fatty acid (FA) composition of plasma FFA and adipose tissue triglyceride (TG). The results are summarized as follows: 1) There were no significant differences between pre- and post-training values in the total plasma FFA. 2) Among the individual FFA at rest, the percentage of saturated FA increased and unsaturated FA decreased as a result of physical training. 3) Comparing trained group with untrained group, similar differences were observed in FA composition of plasma FFA and the adipose tissue TG. There were higher percentage of saturated FA and lower percentage of unsaturated FA in the trained group. The above resluts suggested that FA pattern and FA metabolism of plasma and adipose tissue are changed under the influence of physical training.

Plasma protein binding of etidocaine during pregnancy and labour.

Preliminary studies of the ultrafiltration method for measuring the extent of plasma protein binding of etidocaine showed that etidocaine binding was both pH and concentration dependent. Etidocaine (1 microgram/ml) was found to bind avidly to a physiological concentration (74 mg/dl) of alpha 1-acid glycoprotein (alpha 1-AGP) (7.23 +/- 0.64%, mean +/- SD, unbound). In vitro investigation of etidocaine binding in plasma obtained from blood bank donors and from 19 pregnant women prior to induction of labour, during early labour, mid-labour and delivery showed no difference in etidocaine binding (10.3 +/- 3.3%, 7.06 +/- 2.66%, 8.15 +/- 2.57%, 7.84 +/- 3.74% and 9.28 +/- 6.06% unbound respectively). There was a significant increase in the mean plasma total free fatty acid (FFA) concentration from pre-labour (0.535 +/- 0.240 mM) to delivery (0.948 +/- 0.28 mM), while plasma albumin and beta-lipoprotein concentrations remained constant. Alpha 1-Acid glycoprotein concentration tended to increase slightly from pre-labour to early labour (p less than 0.1) but was still within the normal physiological range. There was no correlation between etidocaine binding ratio and the concentrations of FFA or plasma proteins except for a poor correlation with the alpha 1-AGP concentration (r = 0.361, p less than 0.05). Storage of plasma and inadequate control of plasma pH during ultrafiltration appeared to give spurious binding values. These studies with the extensively bound basic drug etidocaine suggest that unlike many acidic drugs which are bound predominantly to serum albumin, the binding of alpha 1-AGP - bound basic drugs may be unaffected by pregnancy and labour.

Glucose-insulin-potassium induced alterations in individual plasma free fatty acids in patients with acute myocardial infarction

Total and individual plasma free fatty acids (FFA) were measured on admission and over the next 4 days in 24 patients admitted to the hospital with chest pain and suspected acute myocardial infarction (AMI). In a prospective randomized fashion, the patients were either given an infusion of 300 gm of glucose, 50 units of inuslin, and 80 mEq of KCl per liter at a rate of 1.5 ml/kg/hr over the initial 48 hours of hospitalization, or they served as controls receiving conventional therapy. Eleven patients were in the control group and 13 were in the glucose-insulin-potassium (G-I-K) group. Twenty-one of the patients had an AMI by CK-MB rise and ECG changes (in the G-I-K group three did not evolve AMI). The total plasma FFA were 840 ± 134 μM/L in the controls and 933 ± 160 μM/L in the G-I-K group initially (prestudy). Total FFA rapidly fell in the G-I-K group and then rebounded when G-I-K was stopped. In contrast, total FFA values fell gradually in the control group over the 4-day period. The individual FFA had similar percentages initially in the two groups. In the control group the percent of individual plasma FFA was unchanged over the period studied, although there was some mild random day-to-day fluctuation. In contrast in the G-I-K group linoleic acid fell both during and after the infusion was stopped (26.8% to 19.1% P < 0.001). Arachidonic acid doubled in percentage of the total FFA value during G-I-K infusion (3.1% to 6.5%, P < 0.002) and returned to the control value when it was stopped. Thus G-I-K infusion during AMI reduces the total level of plasma FFA while increasing the percent of arachidonic and decreasing the percent of linoleic acid, observations proposed to reflect improved membrane stability of the ischemic myocardium.

Effects of Prolonged Starvation on Plasma Free Fatty Acid Levels and Fatty Acid Composition of Myocardial Total Lipids in the Rat

Experiments were carried out on male rat fed ad libitum or starved for a period of 7 days. Plasma levels of free fatty acids (FFA) and the quantity and composition of fatty acids in total lipids of heart ventricular tissue in vivo were analyzed by gas liquid chromatography (GLC). In addition, FFA extraction ratios and uptake rates were determined in isolated perfused hearts using the classical Langendorff technique. After 7 days of starvation, distribution and concentrations obtained for total lipid fatty acids from heart ventricles of starved animals were substantially different from those of controls. In particular, 20:5 and 22:6 carbon polyunsaturated fatty acids were significantly elevated. Also, total plasma FFA level was elevated and FFA extraction ratios were increased as a result of prolonged starvation. Accumulation of 20- and 22-carbon polyunsaturated fatty acids observed in ventricles of starved rats may have resulted from increased availability and extraction of FFA.

The effect of histamine on the level of plasma free fatty acids in intact and adrenalectomized rats

1. Adult intact and adult adrenalectomized albino rats of both sexes were injected intrafemorally with doses of histamine-2HCl ranging from 0.2 to 10.0 mg/100 g body weight (BW) and from 0.2 to 2.0 mg/100 g BW, respectively. 2. In plasma obtained 10 min after histamine injections, an increase in the level of total plasma free fatty acids was observed in both groups of rats when compared with the pretreatment level of plasma free fatty acids. 3. The increase in total plasma free fatty acids was significant ( P < 0.01) for adrenalectomized rats only.

Placental uptake and transfer of lipid in the postterm rabbit

Gonadotropin-injected pregnant rabbits were delivered by cesarean section near term (30 days after conception) (term, 31 days) and 3 1/2 and 4 days post term. Lipid metabolism of the postterm and near-term fetus was compared. Fetal and placental uptake of radioactivity and rate of lipid entry into the fetus, as well as fetal and maternal plasma free fatty acid (FFA) specific activities (at equilibrium) were determined following a single maternal injection of [1- 14C]palmitate (50 μCi) administered at cesarean section. Evidence of placental malfunction in the postterm period includes decreased placental uptake and transport of labeled FFA occurring while maternal and fetal FFA dynamics (half times) remain unchanged and a loss in “organization”: The strong positive correlation (p < 0.001) between piacental uptake and transfer to the fetus at 30 days' gestation is lost 5 days later. A comparison of maternal and fetal plasma FFA specific activities indicates a substantial (62%) near-term fetal contribution to its own circulating FFA pool. Total plasma FFA is elevated in the postterm fetus concomitant with a decreasing maternal supply. A postterm fetus must therefore contribute lipid from its own reserves (probably liver) in excess of amounts attributed to a near-term fetus, i.e., > 62%.

Influence of Dietary Fatty Acids on Liver and Adipose Tissue Lipogenesis and on Liver Metabolites in Meal-Fed Rats

Rats were trained to eat a fat-free high carbohydrate diet from 800 to 1100 hours each day. After adaptation to meal-eating, the fat- free diet was supplemented with 8% methyl stA©arate(Ci8;o) or 3% methyl linoleate (Ci8:2) for 7 days. Relative to the fat-free group, hepatic utiliza tion of acetate unit equivalents (C2 units) for fatty acid synthesis per mg soluble protein by the Ci8:o group was not significantly altered, whereas Ci8:2 supplementation significantly depressed hepatic fatty acid synthesis. Supplemental Ci8:2 also caused a significant decline in liver fatty acid synthetase and acetyl CoA carboxylase while fat-free and Ci8:o groups dis played similar enzyme activities. Within a treatment, C2 unit utilization tor in vivo fatty acid synthesis was identical to that of acetyl CoA car boxylase and fatty acid synthetase activities in vitro. Therefore, shortly after a meal, the hepatic activities of these two enzymes appear to be functioning at near capacity. Ci8:2 supplementation to the fat-free diet for 7 days caused a 25% decline in glucokinase and pyruvate kinase activ ities, but only pyruvate kinase was significantly depressed. In contrast, citrate cleavage enzyme and fatty acid synthetase were both significantly reduced in activity by 50%. Plasma unesterified fatty acid levels in rats fed Ci8:2 for 5 days were not significantly elevated prior to a meal, al though dietary Ci8:2 did cause a fourfold rise in plasma free linoleate. Quantitation of long chain acyl CoA esters in freeze-clamped liver tissue of rats fed fat-free or fat-free plus 3% Ci8:2 or Ci8:3 diets revealed no con centration differences between treatments either before or after a meal. Similarly, lactate and pyruvate concentrations as well as the lactate: pyru vate ratios were not significantly changed by dietary Ci8:2 or Ci8:3. The inhibitory effects of C18:2 or Ci8;3 appear not to be mediated through changes in total plasma free fatty acid levels, in total hepatic long chain acyl CoA concentration or in hepatic cytosolic redox state. J. Nutr. 107: 1277-1287, 1977.

Influence of Contraceptive Steroids on the Turnover of Plasma Free Arachidonic and Oleic Acids

The turnover of plasma free oleic and arachidonic acids was determined in five healthy women before and after 3 months contraceptive treatment with a daily dose of 0.05 mg ethinyl estradiol and 0.25 mg d-norgestrel administered in a cyclic manner. The contraceptive steroids did not significantly influence the total plasma free fatty acid (FFA) concentration or the turnover of oleic acid. However, during hormone administration the fractional turnover of arachidonic acid increased by 40 per cent and its arterial concentration fell by 20 per cent. The portion of saturated fatty acids in the FFA fraction decreased during the contraceptive treatment. It is concluded that the treatment with contraceptive steroids (1) had no effect on the turnover of the main part of the FFA fraction, (2) increased the transport of the polyunsaturated arachidonic acid through the plasma pool, possibly as an effect of the estrogen component, and (3) stimulated the desaturation of saturated fatty acids to monoenes.

Plasma free fatty acid composition before and after cold exposure in the white rat

1. 1. Free fatty acid (FFA) distribution of blood plasma was analyzed by means of gas chromatography in rats acclimated to room temperature (21–22°C). FFA analysis was carried out on an identically treated group of rats after cold exposure. 2. 2. Total plasma FFA concentration increased by 92 % after cold exposure. 3. 3. Concentration changes were not uniform for all fatty acids examined; the greatest percentage increase was found in palmitic acid.

Plasma free fatty acid and triglyceride transport kinetics in man.

1. Studies were carried out to test the assumptions involved in the calculation of free fatty acid (FFA) and triglyceride transport rates from the plasma radioactivity curves after the intravenous administration of labelled fatty acid or of pre-labelled lipoprotein triglyceride. 2. Plasma FFA equilibrates reversibly with the interstitial lymph. This makes it necessary to use either a pulse injection, with analysis of the results in terms of a two-compartment model, or continuous infusion of the label in determining the FFA flux. 3. The recycling of labelled fatty acid due to direct hydrolysis of plasma triglyceride accounted for less than 5% of the total plasma FFA flux and did not appreciably affect the plasma triglyceride disappearance curve after endogenous labelling with 14C-labelled fatty acid. Turnover values calculated from triglyceride in unfractionated plasma represent mainly the very-low-density lipoprotein triglyceride transport. The distribution space of plasma triglyceride was found to be equal to the plasma volume. 4. Our findings suggest a complex relation between plasma triglyceride concentration and its transport kinetics. The plasma triglyceride concentration is determined by the rates of influx and efflux, and this concentration also regulates its own production and removal. Evidence obtained from the endogenous labelling technique and after experimental hypertriglyceridaemia suggests the application of enzyme kinetic models to characterize plasma triglyceride transport.

The effect of cold exposure on plasma lipids of the new-born and adult ox.

The plasma total free fatty acid (FFA) concentration of ten calves at birth was low, averaging 4·3 mg/100 ml. Five of these animals were exposed to an environment of +25°C immediately after birth, and their plasma FFA concentration increased significantly by 7·5 mg/100 ml. (P 〈 0·05) after the first hour of life. The other five animals were exposed to an environment of +5°C, and they also had a significant increase in plasma FFA concentration after the first hour of life, averaging 25·6 mg/100 ml. (P 〈 0·001). The increase in the group exposed to +5°C was significantly greater than the increase in the group exposed to +25°C (P 〈 0·001). No other plasma lipid fraction altered with change in environmental temperature.Five adult steers exposed to a thermoneutral environment (+15°C) had a mean plasma total FFA concentration of 10·7 mg/100 ml. at the end of 2 hr exposure. In a cold environment (−20°C) this was increased by 8·4 mg/100 ml. (P 〈 0·01) but no other plasma lipid fraction was altered.In one adult animal the adrenal glands were denervated and this had no effect on the increase of plasma FFA in the cold. The other 4 adults were injected with bethanidine, a sympathetic nerve blocking agent, and this reversed the change of plasma FFA concentration at −20°C and also reduced the increase in oxygen consumption which normally occurred at this environmental temperature.It is concluded from these experiments that the plasma FFA concentration of new‐born and adult oxen increases when they are exposed to a cold environment, and in the adult this increase is mediated through the sympathetic nervous system.

Plasma free oleic and palmitic acid levels during vigorous exercise

The behavior of plasma free palmitic and oleic acids was studied without the use of radioactive tracers in fasting human subjects during vigorous exercise and following rest. The initial level of total plasma free fatty acids (FFA) fell during a period of vigorous exercise, and the proportions of palmitic and oleic acids in the total FFA rose and fell, respectively. Further exercise followed by rest resulted in a considerable increase of total FFA level; the proportion of oleic acid rose towards the proportion present in the adipose tissue lipids of the particular subject, while the palmitic acid proportion fell. These changes are interpreted to mean that during muscular activity, uptake of FFA from glasma proceeds in such a manner that oleic acid has a measurably greater fractional turnover rate than has palmitic acid.