Plasma Free Cholesterol Research Articles

Effects of adrenaline infusion on plasma lipids and noradrenaline levels in rabbits with adriamycin-induced cardiomyopathy.

1. We investigated the acute effects of adrenaline infusion on plasma lipid levels in vehicle- and adriamycin-treated rabbits. Lipids were measured before and 30 and 60 min after the commencement of continuous intravenous administration of adrenaline (0.06 microgram/kg per min) or saline in pentobarbital-anaesthetized rabbits. 2. Adrenaline infusion significantly increased plasma free fatty acid (P < 0.05) and noradrenaline (NA) levels (P < 0.05) in vehicle-treated control rabbits, but not in adriamycin-treated rabbits. However, adrenaline had no effect on plasma total cholesterol, free cholesterol, high-density lipoprotein-cholesterol, triglyceride or phospholipid levels. 3. Pretreatment with propranolol almost completely inhibited increased plasma free fatty acid and NA levels associated with adrenaline infusion, suggesting that adrenaline increases plasma free fatty acid and NA levels via the stimulation of beta-adrenoceptors in vehicle-treated rabbits. 4. It is suggested that both the production of plasma free fatty acids and the release of NA via the activation of beta-adrenoceptors is reduced in rabbits with adriamycin-induced cardiomyopathy. This may be related to the down-regulation of beta-adrenoceptors caused by elevated plasma NA levels induced by cardiac failure.

Cholesteryl ester transfer protein activity enhances plasma cholesteryl ester formation. Studies in CETP transgenic mice and human genetic CETP deficiency.

The plasma cholesteryl ester transfer protein (CETP) promotes the removal of HDL cholesteryl esters and is thought to stimulate reverse cholesterol transport (RCT). However, mechanisms by which CETP may stimulate RCT are poorly understood. Thus, we examined the relationship between plasma CETP expression and plasma cholesteryl ester formation in CETP transgenic (Tg) mice, hamsters, and human subjects with genetic CETP deficiency. Incubation of CETP Tg mouse plasma showed a 20% to 40% increase in plasma cholesterol esterification rate (CER, P < .05) compared with control mice. Injection of a neutralizing CETP monoclonal antibody (MAb) (TP2) into natural flanking region CETP Tg mice resulted in an increase in plasma free cholesterol (FC) concentration, FC/CE ratio, FC/phosphatidylcholine ratio, and hepatic CETP mRNA. In hamsters, CETP inhibition also resulted in an increase in plasma FC/phosphatidylcholine ratio and increased CETP mRNA in adipose tissue. In humans with two common CETP gene mutations (an intron 14 splicing defect and a D442G missense mutation), mean plasma CERs were 39 and 60, respectively, compared with 89 nmol x mL-1 x h-1 in normal subjects. By contrast, lecithin:cholesterol acyltransferase (LCAT) mass was normal in CETP-deficient subjects. MAb neutralization of CETP activity in incubated human plasma did not alter the LCAT reaction, even after supplementation with discoidal HDL and VLDL. Thus, genetic alterations in CETP levels lead to secondary changes in the plasma LCAT reaction, possibly because of remodeling of HDL by CETP acting in concert with other factors in vivo. In human genetic CETP deficiency, a moderate impairment in the plasma LCAT reaction may contribute to a defect in RCT, providing a potential mechanism to explain the recently observed excess of coronary heart disease in these subjects.

Effects of dietary cholesterol and triglycerides on lipid concentrations in liver, plasma, and bile.

Dietary cholesterol (CHL) and triglycerides (TG) can influence plasma, hepatic, and biliary lipid composition, but effects on lipids in these three compartments during the early stages of CHL gallstone formation have not been studied in parallel. We fed prairie dogs diets containing one of four test oils (safflower, coconut, olive, or menhaden) at either 5 or 40% of calories, in the presence of 0 or 0.34% CHL, for 3 wk. In the absence of dietary CHL, increases in dietary TG produced 50-200% increases in the concentrations of biliary CHL and hepatic cholesteryl ester (CE), while the concentrations of hepatic free CHL (FC) as well as plasma FC and CE remained relatively unchanged. Increasing dietary CHL to 0.34% resulted in increases in hepatic FC of approximately 50% for all four fats regardless of whether they were supplied at 5 or 40% of calories. CHL supplementation caused more pronounced increases in biliary CHL (200-400%), hepatic CE (50-200%), plasma FC (up to 100%), and plasma CE (up to 150%), and these increases were exacerbated by concurrent supplementation of dietary fat and CHL (biliary CHL: 300-700%; hepatic CE: 100-250%; plasma FC: up to 165%; plasma CE: 100-350%). These results indicate that enhanced secretion of biliary CHL and, to a lesser extent, increased synthesis of hepatic CE, may be primary mechanisms for maintaining the hepatic FC pool. Furthermore, dietary CHL and high levels of fat intake are independent risk factors for increasing biliary CHL concentrations, and adverse effects on lipid concentrations in plasma and bile tend to be exacerbated by ingestion of diets rich in both fat and CHL.

Measuring lipogenesis and cholesterol synthesis in humans with deuterated water: use of simple gas chromatographic/mass spectrometric techniques.

Lipogenesis and cholesterol synthesis can be studied by measuring the incorporation into fatty acids and cholesterol of deuterium from deuterated water. This has been previously achieved in human subjects using low levels of deuterium enrichment in plasma water, and thus in fatty acids and cholesterol. For the measurement of enrichment in lipids, this required the use of isotope ratio mass spectrometry, a tedious and time-consuming technique. It is shown that these measurements can be performed using the much simpler gas chromatography/mass spectrometry if higher, but always safe, deuterium enrichments in plasma water are obtained. Normal subjects ingested deuterated water in order to obtain stable enrichment in plasma water of 0.3% during a 60 h period. Enrichment in palmitate of plasma triglycerides (TG) plateaued (0.6-0.76%) whereas plasma cholesterol enrichment increased progressively [0.32 +/- 0.08% (12 h) to 0.78 +/- 0.18% (60 h)]. Endogenous synthesis was estimated to contribute, in post-absorptive subjects, 8-10% of the plasma TG pool and 3-5% of plasma free cholesterol pool. These data agree with results obtained previously using isotope ratio mass spectrometry. The present method will be useful for studies of normal and abnormal lipid metabolism in humans.

Antiobesity effect of diazoxide in obese zucker rats

Hyperinsulinism and insulin resistance are characteristic findings in obese subjects. Obesity in both humans and experimental animals is associated with a reduced number of insulin receptors and a decreased insulin-mediated glucose disposal, whereas sensitivity to insulin's antilipolytic action is unaltered. To evaluate the antiobesity effect of diazoxide (DZ), an inhibitor of glucose-stimulated insulin release, 7-week-old Zucker obese and lean rats were studied. Obese and lean rats were grouped into DZ-treated (150 mg/kg/d) and control (C) groups. DZ-treated obese rats consumed similar amounts of calories per kilogram body weight (BW) compared with C obese animals, but gained less weight ( P < .01). Postabsorptive plasma free fatty acids (FFA), cholesterol, and triglycerides were significantly higher in obese versus lean animals ( P < .01). DZ treatment reduced plasma triglyceride levels in obese animals ( P < .001), but had no significant effect on FFA or cholesterol concentrations. Plasma glucose concentrations in the postabsorptive state and during glucose tolerance tests (GTTs) were significantly lower in DZ obese versus C obese rats ( P < .01) despite a decrease in plasma insulin concentrations in DZ-treated animals ( P < .01). In contrast, DZ lean rats developed glucose intolerance ( P < .05). Sensitivity and responsiveness to the antilipolytic effect of insulin in isolated adipocytes were significantly decreased in DZ obese as compared with C obese rats ( P < .01). Moreover, adipocyte specific insulin receptor binding was increased in both DZ lean and DZ obese animals ( P < .01). This was accompanied by increased basal and insulin-stimulated glucose transport in both genotypes ( P < .01). In conclusion, DZ increased insulin receptor binding and glucose transport while decreasing hyperinsulinemia and insulin sensitivity to the antilipolytic action of insulin. This combined effect resulted in improved glucose tolerance and a decrease in weight gain in obese rats, implying that pharmacologic modification of the disturbed insulin metabolism of obesity may be therapeutically beneficial.

Lipid changes in plasma and blood cells following intravenous 10% fat infusion in man.

The effects of a 500 ml 4 hr infusion of 10% fat emulsion (Lipovenös) on the lipid content of plasma lipoproteins and blood cells, and on the platelet aggregation rate, were studied in ten volunteers. The infusion resulted in a significant (P < 0.05) initial increase in plasma total triglycerides (more than 5 times), phospholipids (28.7%) and free cholesterol (43.3%), but a decrease in the free cholesterol content of erythrocytes and mononuclear cells (by 4.4% and by 22.7%, respectively). Plasma cholesteryl ester was reduced by 18.2% after the infusion, most of the reduction being accounted for by the 16.5% reduction in high-density lipoproteins. Our findings suggest more than 35% of the free cholesterol accumulated in plasma to derive from peripheral tissues, in turn suggesting overall reverse cholesterol transport from peripheral tissues to plasma to be enhanced. Post-infusion platelet aggregation in response to adenosine disphophate was significantly reduced, the peak rate by 31% and 1 min. rate by 20.6% (P < 0.05 in both cases). These changes in plasma lipids found in normal volunteers suggest that a short-term intravenous infusion of 10% Lipovenös might also be beneficial in preventing atherosclerosis.

Are Bilirubin and Plasma Lipid Profiles of Premature Infants Dependent on the Lipid Emulsion Infused?

The effect of a lipid emulsion containing long-chain triglycerides (LCT) and supplemented with L-carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium-chain triglycerides (MCT). In a double-blind randomized study 49 premature neonates received one of the three fat emulsions, given intravenously, over 16-20 h daily for 6 days. Plasma carnitine levels increased significantly in the supplemented group only; the addition of carnitine did not seem to affect any of the parameters studied. Mean plasma triglycerides rose by 193 and 199% in the carnitine-supplemented and the LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups. Plasma phospholipids and free cholesterol increased (p < 0.05) progressively in all groups and were correlated (r = 0.74, p < 0.001). At the end of the 6-day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids resulting from the stepwise increase in lipid load. No correlation was found between free fatty acids and free bilirubin. Since hyperbilirubinemia and hypertriglyceridemia appear to be clinically independent factors, the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition.

Are Bilirubin and Plasma Lipid Profiles of Premature Infants Dependent on the Lipid Emulsion Infused?

SummaryThe effect of a lipid emulsion containing longchain triglycerides (LCT) and supplemented with L‐carnitine on plasma lipids and bilirubin in premature neonates on total parenteral nutrition was compared to that of lipid emulsions containing either LCT or a mixture of LCT and medium‐chain triglycerides (MCT). In a double‐blind randomized study 49 premature neonates received one of the three fat emulsions, given intravenously, over 16–20 h daily for 6 days. Plasma carnitine levels increased significantly in the supplemented group only; the addition of carnitine did not seem to affect any of the parameters studied. Mean plasma triglycerides rose by 193 and 199% in the carnitine‐supplemented and the LCT groups, respectively, and by 314% in the MCT/LCT group. On the sixth day of the study free fatty acids were significantly higher in the MCT/LCT group than in the other two groups. Plasma phospholipids and free cholesterol increased (p &lt; 0.05) progressively in all groups and were correlated (r = 0.74, p &lt; 0.001). At the end of the 6‐day study all groups showed a similar decline in free and total bilirubin levels despite the significant increase in plasma lipids and free fatty acids resulting from the stepwise increase in lipid load. No correlation was found between free fatty acids and free bilirubin. Since hyperbilirubinemia and hypertriglyceridemia appear to be clinically independent factors, the infusion of lipids should not be withheld from jaundiced infants on total parenteral nutrition.

Altered lipid composition and differential changes in activities of membrane-bound enzymes of erythrocytes in hepatic cirrhosis

Lipid composition, fluidity, and Na +,K +—adenosine triphosphatase (ATPase), Mg 2+-ATPase, and acetylcholinesterase (AChE) activities of erythrocyte membranes were examined in comparison to plasma lipid composition and lecithin:cholesterol acyltransferase (LCAT) activities in 39 patients with hepatic cirrhosis due to viral hepatitis (Child-Pugh class A, n = 12; class B, n = 13; and class C, n = 14). Plasma LCAT activities decreased and the plasma free—cholesterol to phospholipid molar ratio ( C PL ) increased with progressive severity of hepatic cirrhosis. C PL and fluorescence polarization (inverse of fluidity) of erythrocyte membranes also increased with disease progression ( C PL : Child-Pugh A, 0.911 ± 0.010; B, 0.941 ± 0.011; C, 0.979 ± 0.028; and normal, 0.798 ± 0.010; fluorescence polarization: Child-Pugh A, 0.348 ± 0.002; B, 0.351 ± 0.002; C, 0.355 ± 0.002; and normal, 0.340 ± 0.002). There was a correlation between C PL and fluorescence polarization of erythrocyte membranes ( r = .629, P < .001). Na +,K +-ATPase activity of erythrocyte membranes did not differ between cirrhotic patients and normal subjects. On the other hand, Mg 2+-ATPase activity decreased in Child-Pugh C cirrhosis. AChE activity was decreased in Child-Pugh A cirrhosis, and decreased further in Child-Pugh B and C cirrhosis. AChE and Mg 2+-ATPase activities correlated inversely with fluorescence polarization ( r = −.652, P < .001 and r = −.381, P < .01, respectively). These results suggest that the free-cholesterol content of erythrocyte membranes increased in parallel with a decrease in plasma LCAT activity with progression of severity of hepatic cirrhosis, and that a resultant decrease in membrane fluidity affected Mg 2+-ATPase and AChE activities but not Na +,K +-ATPase activity. These membrane-bound enzyme activities may show different dependencies on membrane fluidity.

Effect of apolipoprotein A-I deficiency on lecithin:cholesterol acyltransferase activation in mouse plasma.

Plasma cholesteryl ester (CE) synthesis by lecithin cholesterol acyltransferase (LCAT) is activated by apolipoprotein (apo)A-I. We studied the effect of plasma apoA-I concentration on LCAT activation, using normal, heterozygous or homozygous apoA-I-deficient mice made by gene targeting. Plasma esterified cholesterol concentrations of mice fed chow diets were ordered (mean +/- SEM): 105 +/- 7 (normal) > 70 +/- 5 (heterozygotes) > 26 +/- 2 (homozygotes) mg/dl. Plasma free cholesterol concentrations were similar among the three genotypes. Endogenous LCAT activity, measured as the decrease in plasma free cholesterol after a 1 h incubation at 37 degrees C, was ordered: 44 +/- 3 (normal) > 21 +/- 2 (heterozygotes) > 5 +/- 1 (homozygotes) nmol CE formed/h per ml plasma. Using a recombinant exogenous substrate consisting of egg yolk phospholipid, [14C]cholesterol, and apoA-I, CE formation of normals and heterozygotes was similar (27.4 +/- 0.6 and 28.8 +/- 1.3 nmol/h per ml plasma, respectively), but was significantly less for homozygotes (19.2 +/- 1.7 nmol/h per ml plasma). However, using a small unilamellar vesicle substrate particle containing phospholipid and [14C]cholesterol, CE formation was ordered: 1.6 +/- 0.1 (normal) = 1.6 +/- 0.1 (heterozygotes) > 0.6 +/- 0.1 (homozygotes) nmol/h per ml plasma; addition of apoA-I to the plasma of homozygous animals restored CE formation to normal levels (1.6 +/- 0.1). CE fatty acid analysis demonstrated that plasma from homozygous mice contained significantly more saturated and monounsaturated and fewer polyunsaturated fatty acids compared to normal and heterozygous mice.(ABSTRACT TRUNCATED AT 250 WORDS)

Chronic oat bran intake alters postprandial lipemia and lipoproteins in healthy adults

This study evaluates the possible interaction between chronic oat bran intake and the postmeal metabolic response. Six normolipidemic men consumed three different diets for 14 d, at the end of which they consumed a test meal. The diets were C (control), basal low-fiber diet (15.6 g fiber/d) and a low-fiber (2.8 g fiber) test meal; OB (oat bran), basal low-fiber diet and a 40-g oat bran-enriched test meal (12.8 g fiber); and OB-A (oat bran-adaptation), 14-d oat bran (40 g/d) supplemented diet (23.8 g fiber/d) and an oat bran test meal (12.8 g fiber). The diets were fed in a random order. Fasting and postmeal blood samples were obtained for 7 h and lipoproteins were isolated. Adding oat bran to the test meals markedly reduced the postmeal insulin rise (P < 0.05). Compared with the low-fiber control diet, the effects elicited postprandially by adding oat bran to a single meal were enhanced after 14 d of oat bran feeding, ie, increased plasma triglycerides, phospholipids, and free cholesterol; decreased plasma esterified cholesterol; increased chylomicron and small-sized triglyceride-rich lipoprotein triglycerides; increased LDL and HDL free cholesterol; and decreased HDL esterified cholesterol. Thus, chronic oat bran feeding alters the postmeal response in human subjects.

Analysis of plasma cholesterol oxidation products using gas- and high-performance liquid chromatography/mass spectrometry

The application of gas chromatography and high-pressure liquid chromatography/mass spectrometry techniques for analysis of plasma cholesterol oxidation products is described. Cholesterol oxides that are widely identified in biological samples were subjected to gas (GC) and high-pressure liquid chromatographic (HPLC) separations, and their detection and characterization by mass spectrometry (MS) were compared. Analysis of cholesterol oxides from plasma samples revealed distinct advantages for each method according to the specific cholesterol oxide in question. Whereas HPLC/MS analysis of cholesterol oxides provided less resolution and lower sensitivity as compared to GC/MS, a distinct advantage was evident for direct measurements of cholesterol-7-hydroperoxides and 7-ketocholesterol. These two cholesterol oxides are particularly sensitive to storage in solvents, derivatization procedures, and analytical conditions used for GC analysis, which are minimized or avoided using the HPLC/MS conditions described. Analysis of human and rabbit plasma samples identified cholest-5-ene-3β, 7β-diol (7β-hydroxycholesterol); 5,6α-epoxy-5α-cholestan-3β-ol (cholesterol-5α,6α-epxide); 5α-cholestane-3β,5,5β-triol (cholestanetriol); 3β-hydroxycholest-5-ene-7-one (7-ketocholesterol); and 5,6β-epoxy-5β-cholestan-3β-ol (cholesterol-5β-6β-epoxide) as commonly occurring components (trivial names indicated in parentheses). The latter two compounds were dramatically increased in hypercholesterolemic samples and were found in approximately equal amounts in the free cholesterol and cholesteryl ester fractions. Although most of the plasma cholesterol oxides are found in the dietary cholesterol, others are not, particularly cholesterol-5β,6β-epoxide, suggesting that at least some of these compounds are formed by in vivo oxidation of cholesterol. Despite the readily measurable levels of the above cholesterol oxides, as well as other less prominent oxides, there was no evidence of cholesterol-7-hydroperoxides associated with plasma free cholesterol. Although several of the plasma cholesterol oxides may derive from cholesterol-7-hydroperoxides, it appears that the latter are either unstable and decompose in plasma, are metabolized to other cholesterol oxidation products, or break down during their isolation.

Effects of increasing amounts of dietary cholesterol on postprandial lipemia and lipoproteins in human subjects.

Our aim was to determine the effects of increasing amounts of dietary cholesterol (0-710 mg) on the postprandial plasma lipid responses and lipoprotein changes in normolipidemic human subjects. Ten subjects were fed five different test meals in a random order: one meal did not contain fat or cholesterol while the four others contained a fixed amount of lipids (45 g) and 0, 140, 280, and 710 mg cholesterol, respectively. Fasting and post-meal blood samples were obtained for 7 h. Large and small triglyceride-rich lipoproteins (TRL), low density (LDL), and high density (HDL) lipoproteins were isolated. Compared to the no-fat, no-cholesterol meal, the fat-enriched meals raised (P < 0.05) plasma triglycerides, phospholipids, and free cholesterol and lowered cholesteryl esters postprandially. The meals containing zero or 140 mg cholesterol generally elicited comparable postprandial plasma and lipoprotein lipid responses. The meals providing 280 or 710 mg cholesterol significantly increased postprandial plasma phospholipids and large TRL triglycerides and decreased plasma esterified cholesterol. The lipid composition of the large TRLs and the concentrations of the small TRL lipid components were not altered postprandially by cholesterol intake. On the other hand, LDL free cholesterol increased after 3 h, LDL cholesteryl esters dropped after 3 and 7 h, HDL cholesteryl esters dropped after 3 h, and HDL phospholipids increased 7 h after ingesting meals highly enriched in cholesterol. Blood insulin, apoA-I and apoB were not altered postprandially by cholesterol intake. Thus, the data show that ingesting more than 140 mg cholesterol per meal significantly alters the postprandial lipoprotein response in healthy subjects.

Effects of sodium monensin on reproductive performance of dairy cattle. II. Effects on metabolites in plasma, resumption of ovarian cyclicity and oestrus in lactating cows

A randomised trial was conducted to determine the effects of sodium monensin on plasma metabolite concentrations, resumption of cyclicity and oestrus and milk production and milk composition of postparturient dairy cows. Cows treated with sodium monensin in a controlled-release capsule had significantly lower plasma beta-hydroxybutyrate (BHB) concentrations (P = 0.006) and tended (P = 0.07) to have significantly higher plasma glucose concentrations than untreated cows. Treatment did not significantly influence plasma free fatty acid, urea nitrogen or cholesterol concentrations. Despite higher plasma glucose concentrations and lower plasma BHB concentrations, periods from calving to first ovulation and oestrus were not reduced by treatment. This observation, with limited numbers of cows, is not consistent with a hypothesis that glucose or ketones are important metabolic regulators of pulsatile release of luteinising hormone and consequent resumption of cyclicity. While milk production and milk protein concentration did not significantly differ between groups, milk fat concentration was significantly lower for treated cows. Treated cows probably had lower dry matter intake than untreated cows as they produced 67 litres less milk per head and lost more weight than untreated cows during the study period, although weight and body condition score were not significantly affected by treatment. The lack of significance of these latter observations probably reflects the low statistical power of the study.

Influence of triiodothyronine injections on calf immune response to an infectious bovine rhinotracheitis virus challenge and nitrogen balance of lambs.

Three experiments were conducted to determine the influence of triiodothyronine (T3) or propylthiouracil (PTU) on the humoral immune response of calves challenged with infectious bovine rhinotracheitis virus (IBRV) and on nitrogen depletion and repletion of lambs deprived of feed and water for 3 d. In Exp. 1, 18 steer calves (BW 284 +/- 6 kg) challenged with IBRV were limit-fed (1.5% BW) a 60% concentrate diet and injected (s.c.) daily with alkaline saline, .4 mg of T3, or .8 mg of T3. Injections of T3 did not affect serum antibody titers to IBRV, blood leukocyte counts, or plasma free fatty acid, ceruloplasmin, and cholesterol concentrations but increased (P < .05) plasma glucose concentrations and decreased (P < .05) plasma urea N concentrations. In Exp. 2, 36 IBRV-challenged steers (BW 266 +/- 8 kg) were given ad libitum access to a 60% concentrate diet and injected (s.c.) daily with alkaline saline, .2 mg of T3, or .4 mg of T3. In contrast to Exp. 1, injections of T3 did not affect plasma glucose or urea N concentrations and reduced (P < .05) serum antibody titers to IBRV. In Exp. 3, eight wether lambs were limit-fed (600 g/d) a 36% concentrate pelleted diet and assigned to one of four treatments in a replicated 4 x 4 Latin square designed nutrient balance experiment involving periods of nutrient depletion and repletion. Treatments were as follows: 1) alkaline saline injection (s.c.), 2) 4 mg of PTU/kg BW in water, 3) .15 mg of T3 s.c. daily for 15 d, and 4) .15 mg of T3 s.c. daily for 7 d after the 3-d feed and water deprivation period. Thyroid status affected (P < .05) predeprivation N balance but did not affect N losses during the feed and water deprivation period. Retention of N during realimentation was affected (P < .05) by T3 treatment. Results of these experiments indicate that there is a complex interrelationship among stress, nutrient status, and thyroidal status and that the effects of T3 injections on immune and metabolic responses may be dependent on the nutritional status of the animal.(ABSTRACT TRUNCATED AT 250 WORDS)

Modulation of plasma and hepatic oxidative status and changes in plasma lipid profile by n-3 (EPA and DHA), n-6 (corn oil) and a 3-thia fatty acids in rats

This manuscript describes changes in plasma lipid profiles and parameters of oxidative status in the plasma and liver of rats fed 5 different fatty acids: 95% eicosapentaenoic acid, 92% docosahexaenoic acid (DHA), corn oil (n-6), 1-mono-(carboxymethylthio)-tetradecane (CMTTD) and palmitic acid (controls) for 3 months. At the given doses both EPA and the 3-thia fatty acid, CMTTD, caused a significant decrease in plasma triglycerides, phospholipids, free fatty acids and cholesterol. DHA decreased plasma free fatty acids and cholesterol, while corn oil feeding reduced only plasma free fatty acids. Plasma and hepatic vitamin E levels were significantly decreased in EPA, DHA and CMTTD fed rats, but remained unchanged in corn oil fed rats. Plasma glutathione was noted to decrease after EPA and DHA feeding but remained unchanged in other groups. However, hepatic glutathione content was increased in EPA, DHA and CMTTD fed rats, whereas cysteine levels were noted to decrease. As hepatic levels of cysteinylglycine remained unchanged, increased rate of cellular glutathione synthesis rather than its decreased degradation is likely to contribute to the increased hepatic glutathione content in EPA, DHA and CMTTD fed rats. Except for reduction in the levels of plasma lipid peroxidation caused by CMTTD, no significant changes were noted between the different treatment groups. Hepatic lipid peroxidation was elevated only in rats given DHA. Furthermore, our results show that EPA and DHA cause minimal imbalance of the peroxisomal H 2O 2 metabolising enzymes as compared to CMTTD. In addition, contrary to the potent peroxisome proliferator compound CMTTD which decreased the activities of glutathione transferase and glutathione peroxidase, EPA and DHA increased the activities of these detoxification enzymes.

A31P nuclear magnetic resonance investigation of acyl group transfer from phosphatidylcholine to yield lysophosphatidylcholine in human plasma

31P nuclear magnetic resonance (NMR) spectroscopy was used to measure the rate of acyl transfer from phosphatidylcholine (lecithin, PC) in whole plasma and in high density lipoprotein (HDL). Spectral deconvolution was used to resolve overlapping resonances in the 31P NMR spectra of the phospholipids. Mean values of the acyl group transfer rates from PC in plasma and HDL were 36 mumol L-1h-1 and 19 mumol L-1h-1, respectively. The reciprocal nature of the decrease in the spectral peak intensities of PC, compared to the increase in the intensities of the lysolecithin (lysoPC) peaks, suggested a substrate/product relationship consistent with the action of lecithin:cholesterol acyltransferase (LCAT), the enzyme responsible for the esterification of free cholesterol in plasma. LCAT involvement was confirmed by measuring the cholesterol esterification rate based on the 13C NMR spectra obtained on lipid extracts from plasma that had been incubated at 37 degrees C. Within experimental error, the rate of lysoPC formation in plasma was shown to be equal to that of cholesteryl ester formation.

The Digestibility of Branched-chain Triacylglycerols and Their Effects on Plasma and Hepatic Lipid Levels in the Rat

The digestibility of triacylglycerols (TAGs) comprising branched-chain fatty acids (BCFAs) and the effects on plasma and hepatic lipid levels in rats were investigated by feeding male Sprague-Dawley rats diets containing 5% (w/w) experimental fats for two weeks. Safflower oil (SO), tripalmitoylglycerol (C16TAG), tri-2-methylpalmitoylglycerol (MeC16TAG), and tri-5,9,13-trimethylmyristoylglycerol (Me3C14TAG) were used as experimental fats. The apparent digestibility followed the order of SO>C16TAG>Me3C14TAG>MeC16TAG. Plasma total and free cholesterol levels were significantly lower in the MeC16TAG-fed rats, while plasma HDL-cholesterol level was lower in the Me3C14TAG-fed rats. The plasma TAG level was also very low in the Me3C14TAG group. However, liver lipid level was not influenced by the dietary fat type. 2-Methylpalmitic acid (MeC16) was not detected in liver lipids of the MeC16TAG group although a low level of MeC16 was present in plasma lipids. A low level of 3,7,11-trimethyllauric acid (Me3C12) and ...

Cholesterol and fatty acid metabolism in piglets fed sow milk or infant formula with or without addition of cholesterol

Several studies have reported that plasma cholesterol and phospholipid (PL) levels of arachidonic acid (20:4n−6) are lower and PL levels of linoleic acid (18:2n−6) are higher in infants fed formula than in infants fed human milk. Plasma cholesterol level and possibly the dietary intake of cholesterol could be related to plasma PL n−6 fatty acid metabolism because plasma PL 18:2n−6 is used for esterification of plasma free cholesterol. Whether the low cholesterol content of infant formula as compared with human milk is related to the difference in plasma n−6 fatty acid levels between infants fed human milk and infants fed formula is not known. This study determined the effect of feeding formula with 0.05 mmol cholesterol/L, formula with 1.09 mmol cholesterol/L, or sow milk with 0.34 mmol cholesterol/L on plasma, liver, and bile lipid fatty acid levels and liver low-density lipoprotein (LDL) receptor mass in piglets. Liver microsomal 3-hydroxy-3-methylglutaryl coenzyme A (HMG CoA) reductase activity and plasma lathosterol were assayed as indices of liver and body cholesterol synthesis, respectively. Formula with or without cholesterol added, or sow milk, was fed from birth to 18 days of age. Providing cholesterol in the formula did not correct the significantly lower plasma cholesterol or plasma and liver PL 20:4n−6 levels associated with formula feeding. The liver total cholesterol and cholesteryl esters (CE), biliary bile acid, and PL concentrations were significantly higher and the liver HMG CoA reductase activity and plasma lathosterol:cholesterol ratio were significantly lower in piglets fed the formula with cholesterol than in piglets fed the formula without cholesterol added. No evidence of fewer hepatic LDL receptors was found in piglets fed sow milk compared with piglets fed formula. The results show marked differences in hepatic and bile n−6 fatty acid concentrations between artificially and naturally fed piglets that were not explained by the difference in dietary cholesterol intake alone. The significance of the changes in bile lipid composition due to formula feeding should be studied further.

Heart muscle ubiquinone and plasma antioxidants following cardiac transplantation.

Nine patients who underwent heart transplantation (one female; average age 48 +/- 11, range 19-58 years) were followed in respect to contents of right-sided heart septum, blood and plasma ubiquinone (UQ), plasma alpha-tocopherol (alpha T), and plasma free cholesterol (FC). In contrast to healthy persons, substantial inter- and intraindividual variations were observed; individually low values were seen with rejection. Heart muscle UQ in well-treated patients averaged 0.33 +/- 0.08, range 0.06-0.58 micrograms mg-1 (0.38 +/- 0.09 mumol g-1 dry weight) and was not different from healthy individuals. Plasma UQ, alpha T; and FC averaged 0.63 +/- 0.33 micrograms ml-1 (P < 0.05 versus sedentary controls), 8.1 +/- 4.0 micrograms ml-1 (P < 0.01), and 0.52 +/- 0.23 mg ml-1 (P < 0.05). Corresponding molar values were 0.73 +/- 0.37 (UQ), 2.0 +/- 1.1 mumol l-1 (alpha T), and 1.42 +/- 0.54 mmol l-1 (FC). Blood and plasma UQ values were identical. A saturation like relationship was found between heart and blood UQ:blood contents below 0.7 micrograms ml-1 (0.8 mumol l-1) corresponded to markedly lowered heart contents. In four patients in whom blood samples were taken close to a fatal complication it averaged 0.42 micrograms ml-1 (0.49 mumol l-1, P < 0.01). When low heart muscle and blood ubiquinone were present, other variables such as left ventricle cardiac output or cycle ergometer performance was markedly impaired. Plasma UQ and alpha T covaried with a marker of the lipoidal deposit volume, plasma FC.(ABSTRACT TRUNCATED AT 250 WORDS)