Effect of mesenteric venous volatile fatty acids (VFA) infusion on GH secretion in sheep

The effects of mesenteric venous infusion of acetate, propionate and butyrate mixture (20.3, 40.5 and 81.0 micromol kg[-1] min[-1] over 4 h) on the secretion of GH was examined to investigate the effects of an increase in portal volatile fatty acids (VFA) on GH secretion in relation to inhibition of GH secretion after feeding in sheep. The mesenteric venous infusion at the rate of 40.5 micromol kg(-1) min(-1) increased the portal plasma VFA concentration within the approximate physiological range after feeding. Plasma GH was noticeably suppressed only at the infusion rate of 81.0 micromol kg(-1) min(-1) and the change in the mean concentration from the base line was significantly less than in the control. Although GRF injection rapidly increased plasma GH, the change in the mean concentration from the base line tended to suppress only at the infusion rate of 81.0 micromol kg(-1) min(-1). Plasma FFA was suppressed in a dose-dependent manner after VFA infusion. The change in the mean concentration from the base line was significantly suppressed only at the infusion rate of 81.0 micromol kg(-1) min(-1) relative to the control infusion, but plasma glucose was unchanged by VFA infusion. It is concluded that because the increase in the portal plasma VFA concentration within the range of feeding did not suppress GH secretion, VFA absorbed by the digestive tract may not play a significant role in suppressing GH secretion after feeding in sheep.     

Incorporation of exogenous fatty acids into molecular species of rat hepatocyte phosphatidylcholine

Freshly isolated rat hepatocytes were incubated for 20 and 60 min with [U-14C]glycerol and unlabeled palmitic (16:0), oleic (18:1), or arachidonic (20:4) acid, added as albumin complex in 10% ethanol. Each fatty acid increased glycerol incorporation into total lipids by a factor of 8-10 over control, whereas ethanol alone (final concentration 100 mM) yielded a threefold increase of glycerol uptake. Glycerol incorporation stopped after 20 min and cellular acyl turnover continued in the absence of useable labeled substrate. In each case, radioactivity recovered in hepatocyte lipids was present primarily in triacylglycerol (37-64%), phosphatidylcholine (22-37%), and phosphatidylethanolamine (10-22%). Separation by high-performance liquid chromatography of the diacylglycerol dinitrobenzoates derived from phosphatidylcholine showed that the molecular species had drastically different labeling patterns in the presence of the exogenous fatty acids, whereas the pattern obtained in the presence of ethanol alone was virtually the same as that for the control incubations. The labeling patterns indicated that exogenous fatty acids, including arachidonic acid, were incorporated into phosphatidylcholine primarily by the de novo pathway yielding highly labeled species with the exogenous fatty acid esterified at both the sn-1 and sn-2 positions of glycerol. After 20 min incubation with arachidonic acid, the 20:4-20:4 phosphatidylcholine contained about one-half of the [U-14C]glycerol label recovered in this lipid class. The data also showed that newly synthesized molecular species were extensively remodeled within 1 h.     

Hepatic secretion of VLDL fatty acids during stimulated lipogenesis in men

Fatty acids (FA) that are utilized for triglyceride (TG) synthesis in the liver and principally from two sources: FA synthesized de novo in the liver and preformed FA. We have measured the contribution from the two sources to very low density lipoprotein (VLDL) TG synthesis individually for palmitate, oleate, stearate, and linoleate (approximately 98% of the total FA of VLDL TG (VLDL TGFA)) by isotopomer analysis. Five healthy men were studied in the basal state, and 1 (day 1) and 4 days (day 4) after the start of a hypercaloric carbohydrate-enriched diet (approximately 2.5 times energy expenditure). The secretion of de novo palmitate was increased 15- and 43-fold after 1 and 4 days of hyperalimentation (2.6+/-1.2 (basal state), 40.8+/-20.0 (day 1), and 113.3+/-42.0 micromol/kg per d (day 4)). Even though 4 days of hyperalimentation increased the secretion of de novo stearate 43-fold and de novo oleate 70-fold (stearate; 0.2+/-0.2 (basal), 8.6+/-3.3 micromol/kg per d (day 4), oleate; 0.4+/-0.4 (basal), 28.2+/-12.7 micromol/kg per d (day 4)), palmitate accounted for 75-85% of all the de novo VLDL TGFA. One day of carbohydrate hyperalimentation tended to decrease the secretion while 4 days increased the secretion of all preformed FA in VLDL TG. The rate of secretion of preformed palmitate and oleate were almost identical (palmitate; 80.2+/-22.2 (basal), 45.1+/-23.8 (day 1), and 256.2+/-74.1 micromol/kg per d (day 4), oleate; 95.2+/-22.8 (basal), 46.2+/-24.2 (day 1), and 356.8+/-74.1 micromol/kg per d (day 4)) and collectively these two FA accounted for 80-90% of the secretion from the preformed source. Palmitate is the predominant product of acute and prolonged carbohydrate mediated lipogenesis in the human liver. The pathway of further elongation and subsequent desaturation of de novo synthesized palmitate to generate stearate and oleate is inducible but, quantitatively, of minor significance in hepatic lipogenesis.     

The association between fasting hyperbilirubinaemia and serum non-esterified fatty acids in man

1. The concentrations of plasma total and unconjugated bilirubin and of serum nonesterified fatty acids (NEFA) have been measured in two healthy subjects during fasts of up to 21 h. 2. Fasting was either continuous or interrupted by various procedures that altered the concentrations of NEFA and total bilirubin. 3. When NEFA concentrations were increased by the administration of noradrenaline, heparin or caffeine, bilirubin concentrations also rose. 4. When NEFA concentrations were lowered by insulin, bilirubin concentrations fell. 5. Meals of 3-138 kJ and more, taken during the fasting period, lowered total bilirubin and NEFA concentrations in both subjects, whereas the effects of smaller meals were less consistent. 6. These studies demonstrate a statistically significant correlation between total bilirubin and NEFA during uninterrupted fasting and an association between these variables under other experimental conditions. They suggest that the control of bilirubin concentrations in the blood is linked to lipid metabolism.     

Fatty acids and fatty aldehydes of buffalo seminal plasma and sperm lipid

Analysis of the fatty acids of total and neutral lipids, glycolipids, phospholipids and gangliosides of buffalo spermatozoa and seminal plasma showed that there were high levels of polyunsaturated acids. Neutral lipids were the richest in polyunsaturated acids (55% in spermatozoa and 61% in seminal plasma). The major saturated acid of all the principal classes was stearic acid and the major unsaturated acid was docosahexaenoic acid (22:6omega3) except in the neutral lipids in which it was arachidonic acid (20:4omega6). The major aldehyde was palmitaldehyde (16:0) in buffalo sperm lipids and docosanal (22:0) in seminal plasma. More than 50% of the total aldehydes was contributed by aldehydes with a chain length greater than 18 carbon atoms.     

Divergent incorporation of dietary trans fatty acids in different serum lipid fractions

We isolated from the endogenous polyprenyl-phospho-sugar pool of Mycobacterium smegmatis two mannose-containing compounds, i.e., a partially saturated C35-octahydroheptaprenyl-P-mannose and a fully unsaturated C50-decaprenyl-P-mannose. The relative amount of C35-polyprenyl-P-mannose in mycobacterial cells was comparable to that of decaprenyl- P-pentoses and, at least, an order of magnitude higher than that of C50-decaprenyl-P-mannose. The major form of mycobacterial polyprenyl-P-mannose was structurally characterized by combined gas chromatography-mass spectrometry, fast-atom bombardment tandem mass spectrometry and proton-nuclear magnetic resonance spectroscopy as beta-d-mannopyranosyl-monophospho-(C35)octahydroheptapren ol of which all three isoprene units have Z ( cis ) configuration. The differences in the structure and cellular concentrations of the mycobacterial mannosyl-P-polyprenols reflect distinct biochemical pathways of the two compounds and suggest the existence of specific GDP-Man:polyprenyl-P mannosyltransferases (synthetases) able to distinguish between C35-octahydroheptaprenyl- and C50-decaprenyl- phosphates of mycobacteria. Since the 6'-O-mycoloylated form of C35-octahydroheptaprenyl-P-mannose isolated from M. smegmatis is apparently involved in mycolate rather than mannosyl transfer reactions, we speculate that a catabolic pathway responsible for degradation of C35-P-mannose and recycling C35-octahydroheptaprenyl phosphate might exist in mycobacteria.     

Effect of fatty acids on thyroid function tests in vitro and in vivo

Addition of long-chain fatty acids to serum increased thyroxine (T4), measured by a competitive protein binding assay, and triiodothyronine (T3) uptake by Sephadex or resin (T3U tests). This is compatible with the assumption that fatty acids compete with thyroxine for binding sites on T4-binding proteins. When equimolar concentrations of various saturated and unsaturated fatty acids were added to serum it was observed that the effectiveness in raising tests based on protein binding of thyroid hormones incrreased serum T3 determined by radioimmunoassay (RIA). T4(RIA) was not significantly influenced by either saturated or unsaturated fatty acids. Serum T4(CPB) rose during storage at 22degreesC and 37degreesC but was stable at 4degreesC and --20degreesC for periods up to two weeks. The proportional increase in T4(CPB) and free fatty acids (FFA) indicated that this phenomenon was due, at least partly, to the interference from FFA formed during storage of the serum. There was also a small, significant increase in T3U, T3(RIA) and CT4I (a free thyroxine estimate) after storage of serum at room temperature or higher for one to two weeks. Serum T4(RIA) did not alter during two weeks of storage. In five subjects with raised serum FFA after eating a fat meal followed by a heparin injection an increase in T4(CPB), T3U, T3(RIA) and CT4I that was proportional to the increase in FFA was observed. This effect on the thyroid tests was small until the increase in FFA concentration exceeded 2 mmol/l. T4(RIA) did not respond to the increase in FFA. In ten patients with raised levels of FFA due to uncontrolled diabetes T4(CPB), T4(RIA) and T3(RIA) decreased while T3U increased. These unexpected alterations were probably related to the severe, chronic illness in these patients. Increased FFA in vivo seem to be of little importance for the interpretation of thyroid tests in clinical practice.     

Effect of essential and nonessential fatty acids in complex mixture on fatty acid composition of liver lipids

Linoleate, linolenate, arachidonate, docosahexenoate and six other fatty acids were major components of 24 ester preparations fed as 5% of the diet for 60 days to groups of male white rats. The experiment was designed so as to provide that all major fatty acid components were independent of each other in the sense that the intake of each was poorly correlated with the intake of any of the others. Fatty acid compositions of liver lipids were determined and were related to the composition of the diet lipids. Linolenate and docosahexaenoate contents of diet and tissue revealed the same relationships reported previously from experiments in which individual pure acid esters were added to a fat-free diet. Linoleate, when fed in lipid mixtures, was more effective in raising the linoleate concentration in liver lipids than when fed alone, but this increase did not change the shape of the dose-response curve or the estimated nutritional requirement. Large amounts of fish oil in the diet tended to depress the arachidonate concentration in tissue lipids.     

Essentiality of circulating fatty acids for glucose-stimulated insulin secretion in the fasted rat

We asked whether the well known starvation-induced impairment of glucose-stimulated insulin secretion (GSIS) seen in isolated rat pancreas preparations also applies in vivo. Accordingly, fed and 18-24-h-fasted rats were subjected to an intravenous glucose challenge followed by a hyperglycemic clamp protocol, during which the plasma-insulin concentration was measured. Surprisingly, the acute (5 min) insulin response was equally robust in the two groups. However, after infusion of the antilipolytic agent, nicotinic acid, to ensure low levels of plasma FFA before the glucose load, GSIS was essentially ablated in fasted rats, but unaffected in fed animals. Maintenance of a high plasma FFA concentration by coadministration of Intralipid plus heparin to nicotinic acid-treated rats (fed or fasted), or further elevation of the endogenous FFA level in nonnicotinic acid-treated fasted animals by infusion of etomoxir (to block hepatic fatty acid oxidation), resulted in supranormal GSIS. The in vivo findings were reproduced in studies with the perfused pancreas from fed and fasted rats in which GSIS was examined in the absence and presence of palmitate. The results establish that in the rat, the high circulating concentration of FFA that accompanies food deprivation is a sine qua non for efficient GSIS when a fast is terminated. They also serve to underscore the powerful interaction between glucose and fatty acids in normal beta cell function and raise the possibility that imbalances between the two fuels in vivo could have pathological consequences.     

Acute lowering of plasma fatty acids lowers basal insulin secretion in diabetic and nondiabetic subjects

The objective of this study was to determine whether basal plasma free fatty acid (FFA) concentrations affect basal insulin secretion rates (ISRs). Effects of FFA levels on basal ISRs were evaluated by lowering basal plasma FFA levels with nicotinic acid (NA) (100-150 mg p.o., q 30 min x 4 h) in type 2 diabetic patients and in normal volunteers. Lowering of FFAs (from approximately 600 to approximately 100 micromol/l) lowered ISRs in type 2 diabetic patients during isoglycemic clamping (from 139 to 101 pmol/min; -23%; P < 0.02) and euglycemic clamping (from 99 to 63 pmol/min; -36%; P < 0.03) and in normal subjects during euglycemic clamping (from 127 to 96 pmol/min; -25%; P < 0.03). In addition, peripheral insulin concentrations decreased by approximately 30% in diabetic and nondiabetic subjects. NA had no direct effect on ISRs; that is, NA did not change ISRs when plasma FFAs were prevented from decreasing with a lipid/heparin infusion. We concluded that 1) basal plasma FFAs exerted physiologically important, long-lasting effects supporting 25-33% of basal insulin secretion in nondiabetic and diabetic subjects; 2) basal plasma FFAs were responsible for some of the hyperinsulinemia in normoglycemic obese subjects; and 3) NA had no direct effect on insulin secretion.     

In vitro activity of polyunsaturated fatty acids on Pseudomonas aeruginosa: relationship to lipid peroxidation

The treatment of patients with deep vein thrombosis and pulmonary embolism with contraindications for a thrombolytic therapy is a therapeutic challenge. We report on a 12 year old patient who was treated for large cell lymphoma according to NHL-BFM 95: Block AA protocol. During his therapy, he developed a thrombosis of his right femoral vein and pulmonary embolism affecting the left segments 4, 5, 8, and 9. Because of cerebral metastasis a fibrinolytic therapy was contraindicated. Therefore, we performed a mechanical thrombectomy using the Amplatz thrombectomy device. The postinterventional scintigraphy showed a markedly improved pulmonary perfusion; dopplersonography 4 months postinterventionally showed a patent right femoral vein.     

Drug metabolism in hepatocyte sandwich cultures of rats and humans

Adult hepatocytes from rat and man were maintained for 2 weeks between two gel layers in a sandwich configuration to study the influence of this culture technique on the preservation of basal activities of xenobiotic-metabolizing phase I and phase II enzymes. The response of these enzyme activities to an enzyme inducer was investigated using rifampicin (RIF). Basal levels of cytochrome P-450 (CYP) isozymes were characterized by measuring ethoxyresorufin O-deethylation (EROD), ethoxycoumarin O-deethylation (ECOD), and the specific oxidation of testosterone (T). In hepatocytes from untreated rats, CYP isozyme levels, including the major form CYP 2C11, increased during the first 3 days in culture. After this period of recovery, the levels of CYP 2C11, CYP 2A1, and CYP 2B1 decreased, whereas CYP 3A1 increased. In contrast to these dynamic changes, CYP activities such as CYP 1A2 and the major isozyme CYP 3A4 were largely preserved until day 9 in cultures of human hepatocytes. In measuring phase II activities, a distinct increase in glucuronosyltransferase (UDP-GT) activity toward p-nitrophenol (PNP) was found for rat and human hepatocytes over 2 weeks in culture. Sulfotransferase (ST) activity toward PNP showed an initial increase, with a maximum at day 7 and day 9 in culture, respectively, and then decreased until day 14. Glutathione S-transferase (GST) activity decreased constantly during the time of culture. Effects of the enzyme-inducing drug rifampicin on phase I and phase II enzymes were investigated using cultured human hepatocytes. Rifampicin treatment (50 micromol/L) for 7 days resulted in a 3.7-fold induction of CYP 3A4 at day 9 in culture. ECOD activity was increased sixfold and phase II ST activity increased twofold compared to the initial value at day 3. No effect of rifampicin on CYP 3A was found in cultures of rat hepatocytes. These results demonstrate that rat and human hepatocytes preserve the major forms of CYP isozymes and phase II activities and respond to inducing drugs such as rifampicin. The novel hepatocyte sandwich culture is suitable for investigating drug metabolism, drug-drug interactions and enzyme induction.     

Effect of alcohol on exercise-induced changes in serum glucose and serum free fatty acids

Electrochemical measurements show that there are high-potential states of two copper proteins, Pseudomonas aeruginosa azurin and Thermus thermophilus CuA domain; these perturbed states are formed in guanidine hydrochloride (GuHCl) solution in which the proteins are still blue (azurin) and purple (CuA). In each case, the high-potential state forms reversibly. Absorption (azurin, CuA), visible circular dichroism (azurin, CuA), resonance-Raman (CuA), and EPR (CuA) spectra indicate that the structure of the oxidized copper site of each high-potential form is very similar to that of the native protein. It is proposed that GuHCl perturbs one or more H-bonds in the blue or purple copper active site, thereby allowing Cu(I) to adopt a more favorable coordination structure than that in the rigid cavity of the native protein.     

Acute effects of dietary fatty acids on the fatty acids of human milk

1. Effects on 5-HT function of sibutramine and its active metabolites, BTS 54 354 and BTS 54 505, were compared with fluoxetine, (+)-fenfluramine and (+)-amphetamine. 2. In vitro sibutramine weakly inhibited [3H]-5-HT uptake into brain synaptosomes. BTS 54 354, BTS 54 505 and fluoxetine were powerful [3H]-5-HT uptake inhibitors, whereas (+)-fenfluramine and (+)-amphetamine were very much weaker. Conversely, whilst sibutramine, its metabolites and fluoxetine did not release [3H]-5-HT from brain slices at < or = 10(-5)M, (+)-fenfluramine and (+)-amphetamine concentration-dependently increased [3H]-5-HT release. 3. Sibutramine and fluoxetine had no effect on 5-hydroxytryptophan (5-HTP) accumulation in either frontal cortex or hypothalamus at doses < 10 mg kg(-1). In contrast, (+)-amphetamine ( > or = 3 mg kg(-1)) reduced 5-HTP in hypothalamus, whilst (+)-fenfluramine (> or =1 mg kg(-1)) decreased 5-HTP in both regions. 4. Sibutramine (10 mg kg(-1) i.p.) and fluoxetine (10 mg kg(-1) i.p.) produced slow, prolonged increases of extracellular 5-HT in the anterior hypothalamus. In contrast, (+)-fenfluramine (3 mg kg(-1) i.p.) and (+)-amphetamine (4 mg kg(-1) i.p.) induced rapid, short-lasting increases in extracellular 5-HT. 5. Only (+)-fenfluramine (10 mg kg(-1)) altered 5-HT2A receptors in rat frontal cortex when given for 14 days, producing a 61% reduction in receptor number and a 18% decrease in radioligand affinity. 6. These results show that sibutramine powerfully enhances central 5-HT function via its secondary and primary amine metabolites; this effect, like that of fluoxetine, is almost certainly mediated through 5-HT uptake inhibition. By contrast, (+)-fenfluramine enhances 5-HT function predominantly by increasing 5-HT release. (+)-Amphetamine, though weaker than (+)-fenfluramine, also enhances 5-HT function by release.     

Free fatty acids and cholesterol as possible participants in lipid oxidation radical reactions in animal tissues

Alterations in concentration of free fatty acids, free cholesterol, native antioxidants as well as in the antioxidative activity were studied in lipids of mice liver tissue and small intestinal mucosa. The intensity of free radical reactions in lipids of animal tissues was affected directly by administration of synthetic inhibitors of the reactions. The inverse correlation was observed between the alteration in concentrations of native antioxidants and free fatty acids as well as between the antioxidative activity of lipids and amount of free cholesterol in them. Free fatty acids appears to be the constant participants in the system of free radical oxidation of lipids, while cholesterol can center the system under distinct level of these reactions intensity.     

Tissue specific interactions of exercise, dietary fatty acids, and vitamin E in lipid peroxidation

Both physical exercise and ingestion of polyunsaturated fatty acids that play an essential role in free radical-mediated damages cause lipid peroxidation. The intake of specific fatty acids can modulate the membrane susceptibility to lipid peroxidation. Data confirmed that liver, skeletal muscle, and heart have different capabilities to adapt their membrane composition to dietary fatty acids, the heart being the most resistant to changes. Such specificity affects membrane hydroperoxide levels that depend on the type of dietary fats and the rate of fatty acid incorporation into the membrane. Sedentary rats fed a monounsaturated fatty acid-rich diet (virgin olive oil) showed a higher protection of their mitochondrial membranes against peroxidation than sedentary rats fed a polyunsaturated fatty acid-rich diet (sunflower oil). Rats subjected to training showed higher hydroperoxide contents than sedentary animals, and exhaustive effort enhanced the aforementioned results as well as in vitro peroxidation with a free radical inducer. This study suggests that peroxide levels first depend on tissue, then on diet and lastly on exercise, both in liver and muscle but not in heart. Finally, it appears that alpha-tocopherol is a less relevant protective agent against lipid peroxidation than monounsaturated fatty acids.     

Effect of maternal cholestasis on biliary lipid and bile acid secretion in the infant rat

Monoclonal antibodies specific for haemocyte sub-populations in the mussel, Mytilus edulis, were raised by use of separated basophilic and eosinophilic cell types as antigens. The antibodies could be broadly divided into 3 groups, reactive with sub-populations of (1) basophilic granular haemocytes, (2) basophilic granular and hyaline cells and (3) eosinophilic granular cells. Non-selective antibodies staining all haemocytes were also generated. The antibodies bound to epitopes of differing molecular masses and, at the ultrastructural level, reacted principally with the granules of the haemocyte sub-populations. The antibodies were used to investigate haemocyte function and ontogeny and to test reactivity with haemocytes from mussels subject to varying degrees of pollution stress. Five antibodies showed reactivity with cells from the trochophore and veliger larvae of M. edulis, indicating that epitopes on adult mussel hae-mocytes are also present at much earlier stages in the life history. Reactivity with the larval stages was most prevalent with non-selective antibodies and those selective for basophilic haemocytes. When mussels from different sites were examined, both immunocytochemistry and ELISA showed reduced expression of a 140 kDa epitope in the haemocytes of mussels subject to greater contaminant loads. These results show that the monoclonal antibodies of the present study are valuable both in tracing immune-cell development and in detecting molecular changes under conditions of stress.     

Effects of dithiocarbamates on toxicity of cadmium in rat primary hepatocyte cultures

The protective effects of N-benzyl-D-glucamine dithiocarbamate (BGD) and N-p-hydroxymethylbenzyl-D-glucamine dithiocarbamate (HBGD) on the toxicity of Cd in the rat primary hepatocyte cultures were studied. Cytotoxicity was assessed by measuring cell viability, extra cellular lactic dehydrogenase (LDH) activity, and intracellular lipid peroxidation and active oxygen species. Primary hepatocyte cultures were treated with 109CdCl2 (5, 10 or 50 microM Cd and 1.7 KBq of 109Cd/well) for 30 min or 4 h. BGD or HBGD was added to the culture medium to make the final concentration of 100 microM and incubated for 4.5 h in 30 min Cd exposure or 1 h in 4 h Cd exposure. Decreases in the hepatocyte viability caused by all Cd exposure concentrations were significantly prevented by treatment with BGD or HBGD. The treatment with the chelating agents for 4.5 h after Cd exposure for 30 min significantly prevented increases in extracellular LDH activity. Increases in the lipid peroxidation in hepatocytes exposed to Cd for 30 min or 4 h were prevented significantly by treatment with BGD or HBGD for 4.5 h or 1 h, respectively. Moreover, the increases in the level of active oxygen species caused by Cd exposure for 30 min were significantly prevented by treatment with the chelating agents for 1.5 h. These findings suggest that BGD and HBGD protect against the cytotoxicity of Cd in rat primary hepatocyte cultures and that the protective effects of chelating agents presumably result from a decrease in the Cd level, the effective sequestration of the reactive Cd ion, and the direct preventive effect on the active oxygen species in the hepatocytes.     

Evidence for nonesterified fatty acids as modulators of neutral lipid transfers in normolipidemic human plasma

The relations between the level of plasma nonesterified fatty acid (NEFA) and both the mass concentration and activity of the cholesteryl ester transfer protein (CETP) were studied in fasted normolipidemic subjects. Plasma NEFA correlated positively with both CETP mass concentration (r = .50; P < .01) and the transfer of cholesteryl ester from HDL toward plasma VLDL+LDL (CETHDL-->VLDL+LDL activity) (r = .46; P < .05) but not with the transfer of cholesteryl ester from LDL toward plasma HDL (CETLDL-->HDL activity) (r = .05; NS). The high binding capacity of albumin for NEFA was used to investigate whether lipoprotein-bound NEFAs were implicated in the modulation of the cholesteryl ester transfer reaction. As compared with nonsupplemented controls, the addition of an excess of fatty acid-free albumin (8 g/L) to total normolipidemic plasmas reduced CETHDL-->VLDL+LDL activity (18.3 +/- 5.5% versus 9.8 +/- 3.1%; P < .0001) but not CETLDL-->HDL activity (22.3 +/- 4.5% versus 23.3 +/- 5.1%; NS). Moreover, CETHDL-->VLD+LDL and CETLDL-->HDL activities correlated negatively when measured in native plasma (r = -.45; P < .05) but positively when measured in albumin-supplemented plasma (r = .40; P < .05). In long-term incubation experiments, lipoprotein-bound NEFA increased the net mass transfer of cholesteryl esters from HDL toward VLDL+LDL but reduced the net mass transfer of triglycerides in the opposite direction, from VLDL+LDL toward HDL. Taken together, data of the present study brought strong and concordant arguments in favor of a dual effect of plasma NEFA in modulating both the mass and the activity of CETP in vivo.