Glycerol metabolism alteration in adipocytes from n3-PUFA-depleted rats, an animal model for metabolic syndrome.

Aquaglyceroporin 7 (AQP7) is a glycerol transporter expressed in adipocytes. Its expression has been shown to be modulated in obesity. Metabolic syndrome is characterized by abdominal obesity, insulin resistance, dyslipidemia, and hypertension. An animal model displaying several features of metabolic syndrome was used to study the AQP7 expression at both mRNA and protein level and glycerol flux in adipocytes. Second generation n3-PUFA depleted female rats is a good animal model for metabolic syndrome as it displays characteristic features such as liver steatosis, visceral obesity, and insulin resistance. Our data show a reduced expression of AQP7 at the protein level in adipose tissue from n3-PUFA-depleted rats, without any changes at the mRNA levels. [U-(14)C]-Glycerol uptake was not modified in adipocytes from n3-PUFA-depleted animals.

Hepatic steatosis in n-3 fatty acid depleted mice: focus on metabolic alterations related to tissue fatty acid composition.

BACKGROUND: There are only few data relating the metabolic consequences of feeding diets very low in n-3 fatty acids. This experiment carried out in mice aims at studying the impact of dietary n-3 polyunsaturated fatty acids (PUFA) depletion on hepatic metabolism. RESULTS: n-3 PUFA depletion leads to a significant decrease in body weight despite a similar caloric intake or adipose tissue weight. n-3 PUFA depleted mice exhibit hypercholesterolemia (total, HDL, and LDL cholesterol) as well as an increase in hepatic cholesteryl ester and triglycerides content. Fatty acid pattern is profoundly modified in hepatic phospholipids and triglycerides. The decrease in tissue n-3/n-6 PUFA ratio correlates with steatosis. Hepatic mRNA content of key factors involved in lipid metabolism suggest a decreased lipogenesis (SREBP-1c, FAS, PPAR gamma), and an increased beta-oxidation (CPT1, PPAR alpha and PGC1 alpha) without modification of fatty acid esterification (DGAT2, GPAT1), secretion (MTTP) or intracellular transport (L-FABP). Histological analysis reveals alterations of liver morphology, which can not be explained by inflammatory or oxidative stress. However, several proteins involved in the unfolded protein response are decreased in depleted mice. CONCLUSION: n-3 PUFA depletion leads to important metabolic alterations in murine liver. Steatosis occurs through a mechanism independent of the shift between beta-oxidation and lipogenesis. Moreover, long term n-3 PUFA depletion decreases the expression of factors involved in the unfolded protein response, suggesting a lower protection against endoplasmic reticulum stress in hepatocytes upon n-3 PUFA deficiency.

Vitamin E transfer from lipid emulsions to plasma lipoproteins: mediation by multiple mechanisms.

The present study determined alpha-tocopherol mass transfer from an alpha-tocopherol-rich emulsion to LDL and HDL, and assessed the potential of different mechanisms to modulate alpha-tocopherol transfers. Emulsion particles rich in alpha-tocopherol were incubated in vitro with physiological concentrations of LDL or HDL. The influence of plasma proteins was assessed by adding human lipoprotein poor plasma (LPP) fraction with intact vs heat inactivated PLTP, or with a specific cholesteryl ester transfer protein (CETP) inhibitor, or by adding purified PLTP or pig LPP which lacks CETP activity. After 4 h incubation in absence of LPP, alpha-tocopherol content was increased by ~80% in LDL and ~160% in HDL. Addition of LPP markedly enhanced alpha-tocopherol transfer leading to 350-400% enrichment in LDL or HDL at 4 h. Higher (~10 fold) enrichment was achieved after 20 h incubation with LPP. Facilitation of alpha-tocopherol transfer was (i) more than 50% higher with human vs pig LPP (despite similar PLTP phospholipid transfer activity), (ii) reduced by specific CETP activity inhibition, (iii) not fully suppressed by heat inactivation, and (iv) not restored by purified PLTP. In conclusion, alpha-tocopherol content in LDL and HDL can be markedly raised by rapid transfer from an alpha-tocopherol-rich emulsion. Our results indicate that alpha-tocopherol mass transfer between emulsion particles and lipoproteins is mediated by more than one single mechanism and that this transfer may be facilitated not only by PLTP but likely also by other plasma proteins such as CETP.

Changes in plasma LDL and HDL composition in patients undergoing cardiac surgery.

Changes of lipoprotein composition have been mainly reported in conditions of sepsis. This study characterized compositional changes in LDL and HDL during the acute phase response following cardiac surgery with cardiopulmonary bypass. Twenty-one patients undergoing cardiac surgery were included in this study. Blood samples were drawn before operation and on day 2 post-surgery. In parallel to plasma lipids and antioxidant status, lipoproteins were analyzed for lipid, apolipoprotein (apo), hydroperoxide and alpha-tocopherol content. Beyond decreases in lipid concentrations and antioxidant defenses, cardiac surgery induced substantial modifications in plasma lipoproteins. ApoB decrease in LDL fraction (-46%; P < 0.0001) reflected a marked reduction in the circulating particle number. LDL cholesteryl ester content relative to apoB concentration remained unchanged post-surgery while triglyceride (+113%; P < 0.001), free cholesterol (+22%; P < 0.05) and phospholipid (+23%; P < 0.025) were raised relative to apoB indicating increased particle size. In HDL, an abrupt rise of apoSAA (P < 0.05) was observed together with a decrease of apoA1 (-22%; P < 0.005). Cholesteryl ester content in HDL fraction decreased in parallel to apoA1 concentration while triglycerides, free cholesterol and phospholipids increased relative to apoA1. In contrast to unchanged alpha-tocopherol content, hydroperoxide content was increased in LDL and HDL. By comparison to sepsis, cardiac surgery induces a comparable reduction in circulating LDL but a more limited decrease in HDL particles. Furthermore, in contrast, cardiac surgery induces an increase in polar and non-polar lipids, as well as of particle size in both LDL and HDL.

Intravenous lipid emulsions to deliver omega 3 fatty acids.

A rapid supply of n-3 polyunsaturated fatty acids (PUFA) may be indicated in some acute conditions because of the ability of n-3 PUFA to decrease inflammatory responses and cell sensitivity to various stimuli, and to improve endothelial dysfunction. To achieve these objectives, n-3 PUFA content needs to be quickly raised in cell membranes of key organs. Intravenous fish oil (FO) emulsions are available but their slow hydrolysis limits their infusion rate. Mixtures containing both FO triglycerides and medium chain triglycerides may overcome this problem. These new preparations are rapidly cleared from plasma and efficiently deliver n-3 PUFA to several tissues, largely via direct particle uptake. Recent data suggest that n-3 PUFA incorporation in phospholipids promptly modulates important cell functions. This review also focuses on a novel approach to rapidly supply n-3 PUFA to targeted organs which may offer interesting perspectives in the management of acute illnesses.

Acute in vivo administration of a fish oil-containing emulsion improves post-ischemic cardiac function in n-3-depleted rats.

A novel i.v. lipid preparation (MCT:FO) containing 80% medium chain-triacylglycerols and 20% fish oil was recently developed to rapidly replenish cell membrane phospholipids with omega 3 (n-3) polyunsaturated fatty acids (PUFA). In regard of this property, we investigated the effect of a single i.v. administration of MCT:FO on the recovery of cardiac function after ischemia in control and n-3-depleted rats. Results were compared with those obtained either with a control preparation, where FO was replaced by triolein (MCT:OO), or with saline. Saline (1 ml) or lipid preparation (also 1 ml) was injected as a bolus via the left saphenous vein. After 60 min the heart was removed and perfused for 20 min in normoxic conditions according to Langendorff. Thereafter, the heart was subjected to a 20 min zero-flow normothermic ischemia, followed by 40 min reperfusion. Cardiac mechanical and metabolic functions were monitored. In control rats, the previous administration of a lipid preparation (MCT:FO or MCT:OO) versus saline improved cardiac function during aerobic reperfusion post-ischemia. N-3-depleted rats showed decreased basal cardiac function and impaired recovery following ischemia. However, the bolus injection of MCT:FO opposed the deleterious effect of long-term n-3-deficiency and, in this respect, was superior to MCT:OO over the first 20 min of reperfusion. This novel approach to rapidly correct n-3 PUFA-deficiency might be clinically relevant and offer interesting perspectives in the management of acute ischemic accidents.

Beneficial effects of atorvastatin on sd LDL and LDL phenotype B in statin-naive patients and patients previously treated with simvastatin or pravastatin.

BACKGROUND: The presence of increased levels of small dense (sd) LDL (phenotype B) is associated with a substantial increase of cardiovascular disease risk. Since lowering of plasma low-density lipoprotein-cholesterol (LDL-C) by statins involves an up-regulation of the LDL receptor, we questioned whether LDL lowering by atorvastatin affects different LDL subfractions equally. METHODS: Fifty-four hypercholesterolemic patients, requiring treatment for prevention of coronary heart disease received atorvastatin (10, 20 or 40 mg/day), either as initial therapy (n=33), or as replacement therapy (n=21) for pravastatin or simvastatin (both at 40 mg/day). In addition to plasma lipid measurements, cholesterol LDL subfractions were separated and analysed before and after 3 months of treatment. RESULTS: In addition to the expected LDL-C decrease (-34%; p<0.0001), a major reduction in sd LDL occurred after atorvastatin therapy (-38.2%; p<0.0001). Interestingly, sd LDL decreased as much in patients previously treated with other statins (-36%; p<0.002). A close correlation (r=0.89, p<0.001) was found between reduction of sd LDL and that of LDL-C, in patients with phenotype B. Although high-density lipoprotein-cholesterol (HDL-C) was not affected by atorvastatin treatment, plasma triglycerides decreased by 27.4% (p<0.0001). Only a weak correlation (r=0.35, p<0.01) was found between the reduction of plasma triglycerides and the decrease of sd LDL after atorvastatin treatment. CONCLUSION: These results show that the reduction of LDL-C by atorvastatin largely reflects a lowering of sd LDL. Our data also suggest that triglyceride lowering plays only a partial role in sd LDL reduction.

Tocopherol in lipoproteins and blood cells after cardiac surgery.

Cardiac surgery was associated with a marked reduction in circulating LDL and HDL particles, which in turn largely affectd alpha-toc transport. alpha-toc was decreased in WBCs but not in PLTs and RBCs. An increased hydroperoxide content was observed in LDL and possibly in HDL after cardiac surgery.

Influence of parenteral carbohydrate on fat oxidation in surgical patients.

The administration of parenteral carbohydrate to nutritionally depleted patients in amounts approximating energy expenditure will markedly suppress fat oxidation. If the amount of carbohydrate is increased, net lipogenesis will occur. In contrast, it has been reported that in acutely ill, hypermetabolic patients net fat oxidation continued during the administration of glucose in quantities that exceeded energy requirements. This investigation was undertaken in an attempt to determine to what extent the latter response is due to persistent oxidation of endogenous plasma free fatty acids (FFAs) or stores of lipid in tissue. In this study, carbohydrate intake above energy equilibrium resulted in a 29% increase in CO2 production, a 2% increase in O2 consumption, and an increase in respiratory quotient (RQ) from 0.77 to 0.97 in nutritionally depleted patients. Injured and infected patients displayed a 44% increase in CO2 production and a 15% increase in O2 consumption, while the RQ increased only to 0.9. An isotopic palmitate infusion was used to measure FFA oxidation during parenteral nutrition with variable amounts of carbohydrate. Simultaneous estimates of net fat oxidation were made by indirect calorimetry. At low carbohydrate intakes, oxidation of plasma FFAs accounted for 50% of net fat oxidation in both groups of patients. Suppression of FFA oxidation was greater in the nutritionally depleted patients than in the acutely ill group at intermediate and at high carbohydrate intakes. We conclude that the continued net fat oxidation seen in acutely ill patients receiving high carbohydrate intakes is at least partially due to continuing plasma FFA oxidation. Tissue fat stores that are not in rapid equilibrium with plasma FFAs make a substantial contribution to net fat oxidation.

Energy expenditure, nitrogen balance, and norepinephrine excretion after injury.

In this study we examine the effect of different hypocaloric nutritional regimens on nitrogen balance in patients following total hip replacement and compare it to that of normal subjects on strict bed rest. The interrelationship between nitrogen balance, energy expenditure, and urinary free norepinephrine excretion is analyzed with emphasis on the effects of nutrition on these relationships. Amino acid infusions following major elective orthopedic surgery had no nitrogen-sparing effect above that of 5% dextrose. Optimum nitrogen balance was obtained by administration of both 5% dextose and 3.5% amino acids. Patients receiving 5% dextrose showed no increase in resting energy expenditure in postoperative period compared to the preoperative control value. However, patients receiving amino acid infusions showed a 14% rise in energy expenditure postoperatively. Failure to administer 5% dextrose was associated with a high urinary norepinephrine excretion postoperatively. In normal subjects on bed rest either 5% dextrose or total starvation resulted in a marked fall in resting energy expenditure, whereas amino acid infusions isocaloric to the carbohydrate intake prevented any fall in resting energy expenditure. Nitrogen balance was improved with amino acid infusions in normal subjects. This study suggests the effect of amino acid infusions is highly dependent on the metabolic state of the patient.

Lipoprotein lipase activity in surgical patients: influence of trauma and infection.

Hypertriglyceridemia commonly accompanies clinical sepsis and may be caused by increased hepatic production or decreased clearance of triglyceride from the bloodstream. In contrast, enhanced lipid clearing capacity is usually seen after uncomplicated trauma. The purpose of the study was to determine the role of lipoprotein lipase (LPL) in effecting the above changes. Enzyme activity was assayed in skeletal muscle and adipose tissue biopsy samples from 11 normal subjects and from 17 injured and 11 infected surgical patients. Normal subjects after 4 days of 5% dextrose infusion (D5) showed a significant decrease in adipose tissue LPL activity but no change in skeletal muscle activity. Trauma patients after several days of D5 had higher activity in adipose tissue and higher plasma insulin levels than diet-matched control subjects but showed no change in skeletal muscle activity. Infected patients with high plasma triglyceride levels had significantly decreased LPL activity in both tissues. A linear relationship was found between insulin concentration and adipose tissue LPL activity in normal subjects. We conclude that: (1) low tissue LPL activity in sepsis may result in diminished lipid clearance and contribute to hypertriglyceridemia, (2) after trauma, changes in tissue LPL activity as well as other factors such as altered hemodynamics play a role in determining in vivo lipid clearance, and (3) adipose tissue LPL activity is related to the plasma insulin concentration in normal subjects.

The effect of carbohydrate intake on the lipolytic rate in depleted patients.

The effect of intravenous carbohydrate intake on glycerol turnover and fat metabolism was estimated in six nutritionally depleted surgical patients requiring total parenteral nutrition. Two diets were given. Nitrogen intake was the same in both diets. The calorie intake, adjusted by varying glucose intake, provided either 72% or 128% of the measured resting energy expenditure. Glycerol turnover was measured during administration of 5% dextrose solutions before starting total parenteral nutrition, and again after 4 days on each diet. Turnover rates of glycerol were closely correlated with plasma concentrations. However, fractional turnover rates were only two-thirds of normal values, indicating decreased clearance possibly due to decreased hepatic blood flow. Glycerol turnover, plasma free fatty acid concentrations, and rate of fat oxidation declined progressively with increased glucose intake. When compared with these results, previous studies of injured and septic patients showed: higher values for glycerol turnover, FFA concentrations, and fat oxidation; poor corrlation between glycerol turnover and concentration; inhibition of lipogenesis at high glucose intake; and high rates of norepinephrine excretion. The data suggest that in severe injury, counter regulatory hormones may almost completely block the effects of insulin on hormone sensitive lipase but have less influence on insulin stimulation of FFA esterification and inhibition of ketone body synthesis.

Alterations in plasma alpha- and gamma-tocopherol concentrations in response to intravenous infusion of lipid emulsions in humans.

To study the fate of intravenously infused vitamin E, we infused lipid emulsions rich in gamma-tocopherol (Intralipid, Kabi, Stockholm, Sweden), or in both alpha- and gamma-tocopherols (Lipidem, Hausmann Laboratories, St Gallen, Switzerland); in normal human volunteers. Plasma gamma-tocopherol levels increased in four subjects infused with Intralipid 10% (0.3 g triglyceride [TG]/kg/h for 6 hours) from 3 +/- 1 to 25 +/- 2 nmol/mL, but by 24 hours they decreased to 5 +/- 1 nmol/mL. Although eight times more gamma-tocopherol was infused, plasma alpha-tocopherol levels also increased from 26 +/- 7 to 39 +/- 9 nmol/mL at 8 hours and decreased to 24 +/- 5 nmol/mL at 24 hours. Increases of alpha-tocopherol in the very-low-density lipoprotein (VLDL) density range occurred at 6 and 8 hours, while decreases occurred in low-density lipoprotein (LDL) and high-density lipoprotein (HDL) density ranges at 3, 6, 8, and 24 hours. Infusion of both emulsions in random order to six subjects at therapeutic rates (0.1 g/kg/h for 6 hours) resulted in (1) a threefold increase in plasma gamma-tocopherol concentrations at 6 hours, (2) increases in plasma alpha-tocopherol concentrations only with Lipidem (from 14.3 +/- 1.0 nmol/mL at 0 hours to 18.4 +/- 2.7 at 6 hours and 18.9 +/- 1.1 at 24 hours), and (3) no decreases in lipoprotein alpha-tocopherol levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Some metabolic effects of fat infusions in depleted patients.

Severely depleted surgical patients were given total parenteral nutrition, providing an average of 34.6 kcal and 266 mg nitrogen/kg body weight. Two diets were used, one with glucose as sole source of nonprotein energy, the other with a fat emulsion, Liposyn 10%, substituted isocalorically for one-third of the glucose. The two diets were given alternately, for 1 wk at a time, to each patient. N balance, at zero energy balance, was estimated to average 50 mg nitrogen/kg, indicating that energy intake in excess of expenditure is not required to restore lean body mass in depleted patients. Nitrogen (N) balance was equally good with either diet. Respiratory quotients and carbohydrate oxidation were lower, and fat oxidation was higher with the fat-containing diet. Amino acids and glucose were infused continuously over each 24-hr period and fat was given for only 6--8 hr. During the period of fat infusion, fat oxidation was significantly higher, and carbohydrate oxidation and RQ were lower than at other times of day.

Metabolism of defined structured triglyceride particles compared to mixtures of medium and long chain triglycerides intravenously infused in dogs.

The present study aimed to determine whether including medium-chain fatty acids (MCFA) in specifically designed structured triglycerides (STG) with a MCFA in sn-1 and sn-3 positions and a long-chain (LC) FA in sn-2 position (MLM) would lead to different effects on plasma lipids and FA distribution into plasma and tissue lipids by comparison to a mixture of separate MCT and LCT molecules (MMM/LLL). The fatty acid (FA) composition was comparable in both lipid emulsions. Lipids were infused over 9h daily, in 2 groups of dogs (n = 6 each), for 28 days as a major component (55% of the non-protein energy intake) of total parenteral nutrition (TPN). Blood samples were obtained on specific days, before starting and just before stopping TPN. The concentration of plasma lipids was measured before starting and before stopping TPN on days 1, 2, 3, 4, 5, 8, 10, 12, 16 and 28. Biopsies were obtained from liver, muscle and adipose tissue 15 days before starting, and again on the day following cessation of TPN. In addition, the spleen was removed after the TPN period. FA composition in plasma and tissue lipids was analysed by gas liquid chromatography in different lipid components of plasma and tissues. No differences in either safety or tolerance parameters were detected between both lipid preparations. A lower rise of plasma TG (P < 0.05) was observed during MLM infusion, indicating a faster elimination rate of MLM vs MMM/LLL emulsion. In spite of the differences of TG molecules which would be assumed to affect the site of FA delivery and metabolic fate, FA distribution in phospholipids (PL) of hepatic and extrahepatic tissues did not substantially differ between both emulsions.

Intravascular metabolism of different fatty acids during lipid infusion in man.

The differential intravascular metabolism of individual fatty acids contained in triacylglycerol-rich particles was studied by infusing 6 normal subjects for 5h with a conventional soy-based emulsion and an experimental olive oil-based emulsion. Both emulsions contained similar amounts of palmitate (11%) and stearate (3-4%) but the former was quite rich in linoleate (54%) and alpha-linolenate (7%), while the latter was rich in oleate (69%). During hydrolysis of circulating triacylglycerols by endothelial lipases, the associated rise of non-esterified fatty acids (FFA) in plasma represents the balance between fatty acid release and tissue uptake. Plasma levels of triacylglycerols and FFA increased about 3 fold and total body fat oxidation was raised to similar values with both emulsions. Fatty acid pattern quickly changed in plasma triacylglycerols to resemble the composition of emulsion particles, with an exception for palmitate which increased markedly more, suggesting a high level of hepatic re-esterification and re-appearance in nascent very low density lipoprotein triglycerides (VLDL-TG) secreted into the circulation. In plasma FFA, stearate and palmitate increased more and alpha-linolenate much less than expected from their content in the emulsion, indicating probably low tissue uptake for the former ones but avid removal for the latter.

Lipoprotein metabolism during and after a 6-h infusion ofMCT/LCT vs LCT emulsion in man.

We studied, in man, the intravascular metabolism of two lipid emulsions differing in their triglyceride (TG) fatty acid pattern. One emulsion was composed exclusively of soy bean long-chain triglycerides (LCT), the other of a mixture containing a (1:1, wt:wt) ratio of medium-chain triglycerides (MCT) and LCT (MCT/LCT). Both emulsions contained 10% TG and 1.2% of the same egg yolk phospholipid emulsifier. Six healthy volunteers received both emulsions, in random order, at a rate of 0.2 g TG/kg.h for 6 h. An interval of 2 weeks separated the tests. Although the MCT/LCT emulsion provided 39% more TG molecules than the pure LCT emulsion, plasma TG increased to similar levels, indicating a faster elimination of MCT/LCT. The rise of plasma non esterified fatty acids was greater with MCT/LCT (P < 0.001). LDL-TG enrichment was higher with MCT/LCT (P < 0.025) while net transfer of TG to HDL was similar with both emulsions. Cholesteryl ester (CE) enrichment in the 'VLDL' fraction (largely composed of emulsion particles) was markedly less during MCT/LCT than LCT infusions (P < 0.01). CE enrichment of the 'VLDL' fraction persisted up to 6 h after cessation of both lipid infusions. In conclusion, TG from MCT/LCT emulsion appear to be eliminated faster than LCT during an in vivo infusion in man. In accordance with our previous in vitro data, MCT/LCT infusion was associated with a higher transfer of TG to LDL and in a reverse manner, with a lesser acquisition of CE by emulsion particles as compared to LCT infusion.

Effects of surgery and nutritional support on some lymphocyte and PMN leucocyte functions in man.

The purpose of the present study was to evaluate the effect on some leucocyte functions of 1) an elective surgical procedure; 2) nutritional repletion provided by parenteral alimentation (TPN). The rates of cellular proliferation and protein synthesis in lymphocyte cultures were measured by the incorporation of respectively 3H-thymidine and 3H-leucine; both measures were performed without and with additions of mitogenic agents. Random migration and chemotaxis of PMN leucocytes were measured under agarose. In 10 well-nourished patients, both lymphocyte proliferation and protein synthesis in stimulated cultures decreased after elective surgery, respectively by 50% (p < 0.01) and by 32% (p < 0.05) while random migration of PMN leucocytes was increased by 50% (p < 0.02). Stimulated lymphocyte proliferation and protein synthesis measured in 10 nutritionally depleted non-cancer patients prior to TPN were lower in comparison to the values obtained in a control population (respectively p < 0.006 and p < 0.04). These parameters rose progressively during TPN and reached the normal range after 3 weeks. Before TPN, PMN leucocyte random migration was slower in depleted patients than in control subjects; this parameter reached normal values after one week of TPN, while chemotaxis tended to decrease. Both parameters were in the normal range after 3 weeks of TPN. Conclusions 1) an elective operation depresses lymphocyte functions but stimulates PMN leucocyte random migration in well-nourished patients; 2) in depleted patients, previously depressed leucocyte responses are restored within 3 weeks of adequate nutritional support.

Manipulation of tissue fatty acid profile by intravenous lipids in dogs.

This study was undertaken to determine the effects on the fatty acid (FA) composition of various dog tissues of 4 different lipid emulsions (a 100% long-chain triacylglycerol (LCT) derived from soya bean oil emulsion, a mixed 50% medium-chain triacylglycerol (MCT)/50% LCT emulsion as well as both these emulsions supplemented with 10% fish oil (FO) triacylglycerols), when daily infused over 15 days as a substantial component of total parenteral nutrition. Lipids represented 55% of the non-protein energy. Blood samples as well as biopsies from liver, muscle and adipose tissue were taken 15 days before, and again immediately after TPN. In addition, the spleen was also removed immediately after TPN. Tissue FA composition was analysed by gas liquid chromatography of each lipid component after separation by thin layer chromatography. No differences in either safety or tolerance were detected between the different TPN preparations. In particular, infusion over 2 weeks of fat emulsions containing 10% fish oil was tolerated as well as conventional LCT and MCT/LCT emulsions. Relative linoleate content of tissue triacylglycerol (TG) was markedly increased in animals that received the LCT emulsions (e.g. from 22.6 +/- 2.5% to 32.2 +/- 0.6% in the liver), this effect being markedly reduced with MCT/LCT preparations. n-3FA were slightly incorporated into liver TG (from 0.0 +/- 0.0% to 2.3 +/- 0.7% and 1.2 +/- 0.4% for eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) respectively, with LCT + FO), but remained undetectable in extrahepatic tissue TG. Of interest, medium chain FA were found in tissue TG after infusion of the mixed MCT/LCT emulsions. As expected, changes of tissue phospholipid (PL) composition involved only long-chain FA. Infusion of soya bean oil emulsion was associated with an increased content of linoleate in liver PL (from 13.6 +/- 0.4% to 17.7 +/- 0.4%), but not in other tissues. MCT/LCT did not markedly affect PL/FA pattern in any tissue. Supplementation with fish oil was associated with an efficient incorporation of n-3FA into tissue PL, particularly in the liver (from 0.4 +/- 0.1% to 2.5 +/- 0.3% for EPA and from 3.9 +/- 0.8% to 9.1 +/- 0.4% for DHA, with the LCT + FO emulsion).

Modification of erythrocyte membrane lipid composition induced by a single intravenous infusion of phospholipid-triacylglycerol emulsions in man.

The study aimed to investigate whether, during short term infusion of lipid emulsions in man, red blood cell (RBC) membrane lipid composition was altered and RBC-free cholesterol (FC) could serve as a source of FC accumulated in the plasma. 3 normal subjects were infused intravenously with either 10% Intralipid [10% IL; PL:triglyceride (TG) weight ratio of 0.12] at the rates of 0.1, 0.2 and 0.3 g TG.kg(-1).h(-1) (providing PL intakes of 12, 24, 36 mg.kg(-1).h(-1), respectively) or with 30% Intralipid (30% IL; PL:TG ratio of 0.04) at the rate of 0.3 g TG.kg(-1).h(-1) (providing 12 mg PL.kg(-1).h(-1)). Infusion of 10% IL at a slow rate and 30% IL at a high rate caused no change in RBC and plasma FC content. However, 10% IL infusion at intermediate and high rates induced a significant decrease in RBC-FC: PL ratio. This change was still present at 18 h after the cessation of high rate infusion. RBC-FC: PL ratio and plasma PL measured during infusion were significantly correlated (r = -0.87, p < 0.001). FC efflux from RBC appears to contribute to the rise in plasma FC. This study indicates that the excessive amount of PL present as liposomes in some intravenous lipid emulsions can alter erythrocyte membrane lipid composition.