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).     

Leucine metabolism in preterm infants receiving parenteral nutrition with medium-chain compared with long-chain triacylglycerol emulsions

BACKGROUND: Although medium-chain triacylglycerols (MCTs) may be utilized more efficiently than long-chain triacylglycerols (LCTs), their effect on protein metabolism remains controversial. OBJECTIVE: The aim of the study was to compare the effects of mixed MCT-LCT and pure LCT emulsions on leucine metabolism in preterm infants. DESIGN: Fourteen preterm [gestational age: 30+/-1 wk; birth weight: 1409+/-78 g (x +/- SE)] neonates were randomly assigned to receive, from the first day of life, either a 50:50 MCT-LCT (mixed MCT group; n = 7) or an LCT (LCT group; n = 7) lipid emulsion as part of an isonitrogenous, isoenergetic total parenteral nutrition program. On the fourth day, infants received intravenous feeding providing 3 g lipid, 15 g glucose, and 3 g amino acids kg(-1) x d(-1) and underwent 1) indirect calorimetry and 2) a primed, 2-h infusion of H13CO3Na to assess the recovery of 13C in breath, immediately followed by 3) a 3-h infusion of L-[1-13C]leucine. RESULTS: The respiratory quotient tended to be slightly but not significantly higher in the mixed MCT than in the LCT group (0.96+/-0.06 compared with 0.93+/-0.03). We did not detect a significant difference between the mixed MCT and LCT groups with regard to release of leucine from protein breakdown (B; 309+/-40 compared with 257+/-46 micromol x kg(-1) x h(-1)) and nonoxidative leucine disposal (NOLD; 296+/-36 compared with 285+/-49 micromol x kg(-1) x h(-1)). In contrast, leucine oxidation was greater in the mixed MCT than in the LCT group (113+/-10 compared with 67+/-10 micromol x kg(-1) x h(-1); P = 0.007). Net leucine balance (NOLD - B) was less positive in the mixed MCT than in the LCT group (-14+/-9 compared with 28+/-10 micromol x kg(-1) x h(-1); P = 0.011). CONCLUSION: Mixed MCTs may not be as effective as LCT-containing emulsions in promoting protein accretion in parenterally fed preterm neonates.     

Replacement of long-chain triglyceride with medium-chain triglyceride/long-chain triglyceride lipid emulsion in patients receiving long-term parenteral nutrition: effects on essential fatty acid status and plasma vitamin K1 levels

BACKGROUND: In long-term parenteral nutrition (LTPN) patients, the use of a 50:50 mixture of medium- and long-chain triglyceride emulsion (MCT/LCT) has been suggested to prevent or correct fatty liver infiltration. However, the use of MCT/LCT lipid emulsion results in a 50% reduction of essential fatty acids and vitamin K1 supply and could induce essential fatty acid and vitamin K1 deficiencies. This study evaluated the effect of a long-term infusion of MCT/LCT lipid emulsion on plasma fatty acid (FA) and vitamin K1 levels on LTPN patients. METHODS: In a prospective nonrandomized crossover study, we measured plasma phospholipid FA composition by gas chromatography and vitamin K1 levels by high-performance liquid chromatography in 11 LTPN patients before and after a 4-month replacement of the usual 20% LCT lipid emulsion (20% Lipoven; Fresenius-Kabi France, Sèvres, France) by a 20% MCT/LCT lipid emulsion (Medialipide B; Braun Medical, Boulogne, France). RESULTS: Patient received LTPN for 46 +/- 40 months; IV lipid emulsion was 827 +/- 336 mL/week. MCT/LCT lipid substitution did not change most of the essential plasma fatty acid concentrations and did not induce essential fatty acid deficiency. With both lipid emulsions, the triene/tetraene (20:3n-9/20:4n-6) ratio remained within the normal ranges. However, with MCT/LCT lipid emulsion, 22:4n-6 (LCT: 0.50 +/- 0.12; MCT/LCT: 0.63 +/- 0.11%) and 22:5n-6 (LCT: 0.32 +/- 0.11; MCT/LCT: 0.48 +/- 0.15%) increased significantly (p = .022 and 0.011, respectively). Plasma vitamin K1 levels decreased drastically with MCT/LCT lipid emulsion. CONCLUSIONS: An amount of 2.85 +/- 1.55 g x kg(-1) week(-1) of MCT/LCT lipid emulsion neither induced essential fatty acid deficiency nor improved the fatty acid disturbances usually observed in LTPN patients but did induce a drop in plasma vitamin K1 levels.     

Inclusion of 10% fish oil in mixed medium-chain triacylglycerol-long-chain triacylglycerol emulsions increases plasma triacylglycerol clearance and induces rapid eicosapentaenoic acid (20:5n-3) incorporation into blood cell phospholipids

BACKGROUND: Lipolysis of a fish oil (FO) emulsion is much slower than that of a soybean [long-chain triacylglycerol (LCT)] emulsion; in contrast, emulsions containing medium-chain triacylglycerol (MCT) are efficiently hydrolyzed by lipoprotein lipase. OBJECTIVES: We questioned whether incorporating 10% FO in a mixed MCT-LCT emulsion would affect plasma triacylglycerol clearance and provide efficient delivery of n-3 polyunsaturated fatty acids to cells and tissues. DESIGN: This prospective crossover study was conducted in 8 normolipidemic subjects with the use of the hypertriglyceridemic clamp model and compared plasma triacylglycerol clearance of a lipid emulsion (5:4:1) made of 50% MCT, 40% LCT, and 10% FO (wt:wt:wt) to a control (5:5) preparation with 50% MCT and 50% LCT. Subjects were daily infused for 5 h, over 4 consecutive days. Fatty acyl pattern was daily measured in plasma phospholipids as well as in leukocyte and platelet phospholipids. RESULTS: Inclusion of 10% FO in mixed emulsion particles enhanced plasma clearance of infused triacylglycerols (18%; P < 0.0001). The faster elimination of the 5:4:1 emulsion appears related to an enhanced uptake of remnant particles rather than to faster intravascular lipolysis. Each infusion of 5:4:1 raised the eicosapentaenoic acid (C20:5n-3) concentration in blood cell phospholipids to reach a 7-fold enrichment in platelets and a >2-fold enrichment in leukocytes after 4 infusions. In contrast, the docosahexaenoic acid (C22:6n-3) concentration remained unchanged in blood cell phospholipids. CONCLUSIONS: Infusion of a mixed emulsion with MCTs, soy LCTs, and FO is associated with efficient plasma triacylglycerol clearance and results in rapid incorporation of C20:5n-3 but not C22:6n-3 in leukocyte and platelet phospholipids.     

Long-chain versus medium-chain lipids in acute pancreatitis complicated by acute respiratory distress syndrome: effects on pulmonary hemodynamics and gas exchange

BACKGROUND AND AIMS: In order to assess the effects of fat emulsions in patients with acute pancreatitis and acute respiratory distress syndrome (ARDS) before the pancreatic injury was complicated by infection, pulmonary hemodynamics and gas exchange were investigated during the administration of long-(LCTs) or medium-chain triacylglycerols (MCTs). METHODS: This prospective trial included nine patients with acute pancreatitis and ARDS; each patient was used as his/her own control. In all cases, the needle aspiration culture of the pancreas was negative. Fat emulsion provided 50% of the energy expenditure. The patients were infused, in random order, with pure LCTs and a 1:1 mixture of LCTs/MCTs on days 1 and 2, over an 8 h period. RESULTS: LCT infusion increased the mean pulmonary artery pressure (MPAP) from 28+/-5 to 35+/-3 mmHg, pulmonary venous admixture (Qva/Qt) from 26+/-5% to 36+/-5% and decreased arterial PO2(PaO2)/fractional inspired oxygen (FIO2) from 210+/-20 to 170+/-20 (P<0.05). The infusion of LCT/MCT 1:1 emulsions increased oxygen consumption (VO2) from 340+/-10 to 398+/-15 ml/min, cardiac output (CO) from 8.8+/-0.2 to 9.5+/-0.5 L/min and CO2 production (VCO2) from 247+/-12 to 282+/-14 mL/min (P<0.05). CONCLUSION: LCT/MCT 1:1 mixtures are recommended in cases of acute pancreatitis and ARDS, even though infusion over a short period increases the metabolic demand.     

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.     

Clinical and metabolic effects of two lipid emulsions on the parenteral nutrition of septic patients

OBJECTIVE: We compared the metabolic and clinical effects of two lipid emulsions, long-chain triacylglycerols (LCT) and a mixture of medium- and long-chain triacylglycerols (MCT/LCT), in septic patients. METHODS: Both groups received total parenteral nutrition (TPN) with a solution enriched with branched-chain amino acids (BCAA). Seventy-two septic patients received TPN with MCT/LCT (group 1) or LCT (group 2). Before starting TPN (basal) and 10 d after (final), various parameters were evaluated. RESULTS: Twenty-six subjects in each group completed the study. Both groups showed an increase in cholestasis enzymes, with no significant changes in lipid parameters. The rise of retinol-binding protein and the recovery of nitrogen balance were significantly greater in group 1. A multivariate analysis of nutritional markers and catabolic parameters showed a better evolution in group 1 (P = 0.002). The MCT/LCT group exhibited a significant increase of insulin levels. Overall mortality and length of stay in the intensive care unit were not affected by the lipid emulsion. CONCLUSIONS: In septic patients who received TPN with a solution enriched with BCAAs, the use of an emulsion containing MCT provided them with a greater recovery of their nutrition status than the traditional LCT formula, without influencing the outcome.     

Changes of hepatic morphology during parenteral nutrition with lipid emulsions containing LCT or MCT/LCT quantified by ultrasound.

Fatty infiltration of the liver with cholestasis is one of the complications of total parenteral nutrition (TPN). The cause has not yet been determined. It seems probable, however, that these alterations could be prevented when a mixture of medium- and long-chain triglycerides (MCT/LCT) is used as a fat component instead of the application of long-chain emulsions (LCT) alone. To determine whether this could also be demonstrated morphologically in man, 14 patients needing TPN (25 kcal/kg BW x day, carbohydrate 45%, fat 35%, protein 20%) were examined by ultrasound in order to compare liver size and gray-scale value before and after 7 days of TPN. Seven of the patients were randomly administered a MCT/LCT emulsion as their fat intake, the other seven were exclusively given LCT. There were no changes in liver size and gray-scale value in the MCT/LCT-group, whereas both parameters showed a significant rise in the patients with LCT (size: 10.4 +/- 1.4 to 11.5 +/- 1.4 cm; gray-scale value: 9.3 +/- 1.0 to 11.6 +/- 0.7). These data suggest that TPN, administered with a mixture of MCT/LCT emulsions as fat components, could reduce the risk of hepatic dysfunction such as cholestasis and fatty infiltration of the liver.     

A new intravenous emulsion containing medium-chain triglyceride: studies of its metabolic effects in the perioperative period compared with a conventional long-chain triglyceride emulsion

The effects of carbohydrate, lipid, and nitrogen metabolism of recently available lipid emulsions containing either 50% medium-chain triglyceride (MCT) and 50% long-chain triglyceride (LCT) or 100% LCT were compared in elective surgical patients. Postoperative urinary urea excretion was similar during isocaloric MCT/LCT and LCT infusions (1.9 mg/kg/min) and was decreased compared with a standard infusion of 5% glucose (1 mg/kg/min). Plasma glucose and insulin concentrations were similar during both lipid and low dose glucose infusions. However, plasma triglyceride and nonesterified fatty acid concentrations were decreased during the MCT/LCT infusion compared with the LCT infusion, suggesting that the MCT/LCT emulsion was cleared from the circulation faster than pure LCT. Ketone body concentrations were similar during all three infusions. MCT/LCT emulsion can be safely infused perioperatively and has similar nitrogen conserving properties to LCT in these circumstances.     

Brain lipid composition in rabbits after total parenteral nutrition with two different lipid emulsions

ObjectiveTo study the changes occurring in brain lipid composition after the administration of total parenteral nutrition (TPN) by comparing two lipid emulsions, one with long-chain triacylglycerols (LCT) and the other with long-chain and medium-chain triacylglycerols (MCT/LCT 50%/50%).MethodsWe used 21 young New Zealand rabbits divided into three groups of seven animals each. Two groups were subjected to TPN for 7 d, with each group receiving using one of two different lipid emulsions: Intralipid 20% (group LCT) and Lipofundin MCT/LCT 20% (group MCT/LCT). The third control group received an oral diet and underwent the same surgical procedure with the administration of intravenous saline solution. The energy administered in the TPN formulas was non-protein 100 kcal ? kg^?1 ? d^?1, with 40% corresponding to fats.ResultsThere were modest increases in plasma cholesterol and triacylglycerols. In the brain tissue, there was a decrease of phosphatidylcholine in animals with TPN, which was greater in group LCT. There were no significant differences in the overall percentage distribution of brain fatty acids among the groups.ConclusionThe lipid emulsions administered in TPN, especially those prepared exclusively with LCT, cause changes in the brain lipid polar fractions of young rabbits.     

Effects of medium-chain and long-chain triacylglycerols in pediatric surgical patients

Medium-chain triacylglycerols (MCTs) have been shown to provide better nutritional support than long-chain triacylglycerols (LCTs). This study compares the efficacy of MCT combined with LCT with LCT alone in pediatric patients with surgical stress. Two groups of patients (n = 19 in each) received equivalent amounts of glucose (12 g. kg. d) and amino acids (2 g. kg. d), but one group received 10% Lipofundin MCT/LCT and the other received 10% LCT (1.5 g. kg. d) in a randomized study. Total parenteral nutrition (TPN) was given for 14 d. Blood and urine samples were collected before and after TPN administration for determination of various biochemical parameters. Indirect calorimetry was also performed to determine respiratory quotients and fuel utilization. After 14 d of TPN in the MCT/LCT group, there was a significantly higher blood lymphocyte percentage, a decreasing tendency of serum asparate aminotransferase and of total and direct bilirubin (P < 0.05). These changes were not observed in the LCT group. A significantly better nitrogen balance and a higher ketogenesis from day 3 were observed in the MCT/LCT group. The MCT/LCT group showed a more marked increased utilization of fat than the LCT group, whereas carbohydrate oxidation was less in the MCT/LCT group than in the LCT group (P < 0.05). In children after surgery, MCT/LCT is more protein sparing and induces a better immune response when compared with LCT-containing lipid emulsion. A TPN regimen containing MCT/LCT is likely to result in rapid oxidation of fats for energy without compromising the respiratory system.     

Energy expenditure in rats maintained with intravenous or intragastric infusion of total parenteral nutrition solutions containing medium- or long-chain triglyceride emulsions.

Energy expenditure was determined in male Fischer 344 rats (235-246 g) fed by intravenous (IV) or intragastric (IG) infusion with total parenteral nutrition solutions providing 65% of nonprotein energy as fat from long-chain triglyceride (LCT) or a 3:1 admixture of medium-chain triglyceride (MCT) and LCT emulsions. Respiratory gas exchange and somatomotor activity were assessed continuously for 24 h during d 5 and 11 of infusion feeding. The MCT infusion resulted in one-third the weight gain noted with LCT infusion (MCT, 10 +/- 2 g/14 d; LCT, 32 +/- 4 g/14 d; P less than 0.0001). Insulin concentration was 60% higher with IV than with IG infusion and approximately 100% higher with IV-MCT than with IG-MCT or LCT infusion (P less than 0.05). Rats receiving IV infusion of MCT displayed similar levels of motor activity but 8-13% greater daily energy expenditure (kJ.kg-0.75.kJ intake-1) than rats receiving IG-MCT or LCT infusion (P less than 0.05). The MCT infusion also resulted in an elevation in respiratory quotient after cessation of nutrient infusion (MCT, 0.87-0.92; LCT, 0.83-0.85; P less than 0.05). Total and resting energy expenditure decreased approximately 13% from 5 to 11 d of infusion feeding. The lower weight gain and greater energy expenditure seen with MCT- compared with LCT-supplemented total parenteral nutrition may be mediated by higher insulin concentrations.     

Fat elimination in acute renal failure: long-chain vs medium-chain triglycerides.

Elimination and hydrolysis of fat emulsions containing long-chain (LCT; Intralipid) or long- and medium-chain triglycerides (MCT; Lipofundin MCT) were compared in seven patients with acute renal failure (ARF) and six healthy control subjects. In control subjects, clearance of MCT was slightly higher than that of LCT (1.93 +/- 0.34 vs 1.55 +/- 0.3 mL.kg body wt-1.min-1, P less than 0.05). The rise in plasma triglycerides was similar and the release of free fatty acids was higher during MCT (P less than 0.02). In ARF, clearance of both LCT and MCT was equally reduced (0.53 +/- 0.12 vs 0.59 +/- 0.14 mL.kg body wt-1.min-1, P less than 0.01 vs control subjects). Again, the rise in triglycerides was comparable. Free fatty acid release was higher during MCT but lower than in control subjects. Plasma concentrations of glucose and lactate were not affected in control subjects but increased during both LCT and MCT in ARF. Thus elimination of both LCT and MCT is profoundly decreased in ARF. The impaired lipolysis in ARF cannot be circumvented by the use of MCT.     

Lipid infusion with different triglyceride cores (long-chain vs medium-chain/long-chain triglycerides): effect on plasma lipids and bilirubin binding in premature infants.

The possible beneficial effects of infusing a lipid emulsion containing 50% by weight of medium-chain triglycerides (MCT) compared with a standard long-chain triglyceride (LCT) emulsion were studied in 18 premature neonates (gestational age less than 34 weeks) requiring parenteral nutrition. The infants were assigned in a double-blind manner to receive one of the two lipid emulsions over 17 hours a day as a supplemental regimen for total parenteral nutrition. A lipid load of 1 g/kg per day was initiated on the third day of life and was increased at the rate of 1 g/kg per day until a maximal dose of 3 g/kg per day was obtained on the fifth day of life and maintained thereafter. Both bound and unbound bilirubin decreased with both infusion regimens during the study period. Despite a marked increase in plasma free fatty acid levels (260% in the MCT/LCT group compared with 210% in the LCT group), the fraction of unbound (free) bilirubin was significantly lower in the MCT/LCT group (34% vs 13%). Free fatty acid levels, corrected to albumin, were positively correlated to the percentage of free bilirubin only for the LCT lipid infusion. The finding of a significant elevation of plasma cholesterol levels only in the MCT/LCT group is now under investigation. Use of the MCT-containing emulsion was not associated with a higher frequency of adverse effects than the commonly used LCT-containing emulsion.(ABSTRACT TRUNCATED AT 250 WORDS)     

Feeding behavior in neonates whose diet contained medium-chain triacylglycerols: short-term effects on thermoregulation and sleep

BACKGROUND: Feeding formulas for premature infants often contain medium-chain triacylglycerols (MCTs). However, previous studies in animals and adults showed that MCTs may decrease food intake. OBJECTIVES: The objectives were to determine in hospitalized premature infants whether food intake is modified by dietary MCT supply and to assess the effects on thermoregulation and sleep, which are involved in the regulation of energy metabolism and in the optimal physiologic development of the neonates. DESIGN: Food intake, body mass, and nutritional efficiency during 3 consecutive days were compared in 2 groups of neonates according to the fat composition of their feeding formula [MCT group: 37% MCT, 63% long-chain triacylglycerols (LCTs); LCT group: 100% LCT]. On the third day, sleep and metabolic rate were recorded in the morning during an interval between meals. RESULTS: Regardless of day, energy intake was greater in the MCT group than in the LCT group (x difference: 67.3 kJ x kg(-1) x d(-1); P = 0.007). Metabolic rate (1.8 mL x min(-1) x kg(-1); P < 0.001), cheek skin temperature (0.31 degrees C; P = 0.04), and total sleep time (52 min; P = 0.01) were also higher in the MCT group. CONCLUSION: The ratio of MCTs to LCTs in neonates' feeding formulas can modify physiologic functions involved in energy-balance regulation.     

Studies on the tolerance of medium chain triglycerides in dogs

Two groups of five conscious dogs received total parenteral nutrition (about 100 kcal/kg body weight per 24 hr) continuously for 96 hr (0.28 g triglycerides/kg body weight per hr, constituting more than 55% of the energy supply). The only difference between the two groups was the nature of the 20% lipid emulsion. In one group, this emulsion contained only long-chain triglycerides (LCTs), and in the other it contained a mixture (vol/vol) of medium chain triglycerides (MCTs) and LCTs. MCTs thus were given in an amount of about 30% of the total energy supplied. During infusion with the MCT/LCT mixture, C8, C10, and C12 fatty acids appeared in the total plasma fatty acids. When the infusion was stopped, the medium-chain fatty acids disappeared; those with shorter chains did so more rapidly. The plasma triglyceride clearance was faster for the MCT/LCT mixture than for the LCTs, whereas phospholipid and cholesterol clearance seemed slower for the MCT/LCT mixture. With this mixture, there was a slight increase in the plasma concentrations of ketone bodies, lactate, and pyruvate, and a slight decrease in plasma glucose. The MCT/LCT mixture was well tolerated, causing no discernible problems, and, in particular, no signs of narcosis or encephalopathy.     

Competitive effects of long-chain-triglyceride emulsion on the metabolism of medium-chain-triglyceride emulsions

This study was conducted to assess the potential metabolic competitive interactions of intravenous medium-chain-triglyceride (MCT) and long-chain-triglyceride (LCT) lipid emulsions. To assess this competition increasing concentrations of LCT emulsion were added to an intravenous dose of MCT emulsion of 3.0 g/kg body wt up to a maximum dose of 3.0 g LCTs/kg body wt. Blood samples were assessed for competitive interactions by analyzing the following metabolites: glucose, insulin, lactate, pyruvate, ketones (acetoacetate, beta-hydroxybutyrate), elimination of triglycerides, and free fatty acids. Evaluation of the data showed a strong competitive interaction between the MCT and LCT emulsions. This competition was evident as soon as LCTs were added to the MCT infusions and appeared to favor LCTs for removal and metabolism over MCTs. This appears to indicate that there is a peripheral, strong affinity site for LCT removal and metabolism and a shared peripheral site and specific visceral site for MCT removal and metabolism.     

Effects of parenteral structured lipid emulsion on modulating the inflammatory response in rats undergoing a total gastrectomy

OBJECTIVES: Structured lipid emulsion improves the nitrogen balance and is rapidly cleared from the blood of moderately catabolic patients. However, the effects of structured lipids on inflammatory reactions during major surgery are not clear. This study investigated the effect of a parenteral structured triacylglycerol emulsion on leukocyte adhesion molecule expression and inflammatory mediator production in rats undergoing a total gastrectomy. METHODS: Normal rats with internal jugular catheters were assigned to three experimental groups and received total parenteral nutrition. At the same time, a total gastrectomy was performed on the experimental groups. The total parenteral nutrition solutions were isonitrogenous and identical in nutrient compositions except for differences in the composition of the fat emulsion. Group 1 received a conventional fat emulsion with long-chain triacylglycerols (LCTs), group 2 received a physical mixture of medium-chain triacylglycerols (MCTs) and LCTs (MCT/LCT), and group 3 received structured lipids composed of MCTs and LCTs (STG). Half of the rats in each respective group were sacrificed 1 d and the other half 3 d after surgery to examine the analytical parameters. RESULTS: Plasma cholesterol and free fatty acid levels in the STG group were lower than those in the other groups after surgery. The STG group had lower leukocyte CD11a/CD18 expressions than the MCT/LCT group 3 d after surgery, and CD11b/CD18 expressions in the STG group were lower than those in the LCT group on postoperative days. The STG group had higher monocyte chemotactic protein-1 and macrophage inflammatory protein-2 levels in peritoneal lavage fluid than did the other two groups. CONCLUSION: These results suggest that, compared with the LCT and MCT/LCT groups, rats administered STG had lower plasma lipid concentrations and leukocyte integrin expressions. In addition, STG administration may cause increased recruiting of neutrophils and monocytes at the site of injury and enhance antipathogenicity in rats undergoing a total gastrectomy.     

Human leukocyte death after a preoperative infusion of medium/long-chain triglyceride and fish oil parenteral emulsions: a randomized study in gastrointestinal cancer patients

Background: Parenteral lipid emulsions (LEs) can influence leukocyte functions. The authors investigated the effect of 2 LEs on leukocyte death in surgical patients with gastrointestinal cancer. Material and Methods: Twenty-five patients from a randomized, double-blind clinical trial (ID: NCT01218841) were randomly included to evaluate leukocyte death after 3 days of preoperative infusion (0.2 g fat/kg/d) of an LE composed equally of medium/long-chain triglycerides and soybean oil (MCTs/LCTs) or pure fish oil (FO). Blood samples were collected before (t0) and after LE infusion (t1) and on the third postoperative day (t2). Results: After LE infusion (t1 vs t0), MCTs/LCTs did not influence cell death; FO slightly increased the proportion of necrotic lymphocytes (5%). At the postoperative period (t2 vs t0), MCTs/LCTs tripled the proportion of apoptotic lymphocytes; FO maintained the slightly increased proportion of necrotic lymphocytes (7%) and reduced the percentage of apoptotic lymphocytes by 74%. In the postoperative period, MCT/LCT emulsion increased the proportion of apoptotic neutrophils, and FO emulsion did not change any parameter of apoptosis in the neutrophil population. There were no differences in lymphocyte or neutrophil death when MCT/LCT and FO treatments were compared during either preoperative or postoperative periods. MCT/LCTs altered the expression of 12 of 108 genes related to cell death, with both pro- and antiapoptotic effects; FO modulated the expression of 7 genes, demonstrating an antiapoptotic effect. Conclusion: In patients with gastrointestinal cancer, preoperative MCT/LCT infusion was associated with postoperative lymphocyte and neutrophil apoptosis. FO has a protective effect on postoperative lymphocyte apoptosis.     

Effects of structurally different lipid emulsions on human neutrophil migration

AIM: To test the hypothesis that structurally different lipid emulsions have distinct immunomodulatory properties, we analysed neutrophil migration in the presence of various lipid emulsions. METHOD: Neutrophils of 8 volunteers were pre-incubated in medium or physiological 2.5 mM emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, alpha -tocopherol-enriched LCT/MCT (LCT/MCT-E) or structured triglycerides (SL). Thereafter, the cells were put on top of 3 microm-pore-sized cell culture filters and incubated for one hour in the presence or absence of a chemo-attractant. Neutrophil migration was measured as the percentage of cells that had passed the filter in the presence (chemotaxis) or absence (random migration) of a chemotactic factor. RESULTS: Compared to lipid-free incubation (19+/-1%) random neutrophil migration significantly decreased with LCT/MCT (11+/-2%), LCT/MCT-E (12+/-2) and MCT (5+/-2%), while LCT (18+/-3%) and SL (20+/-1%) had no effect. N-formyl-methionyl-leucyl-phenylalanine- (fMLP, 10(-8)M) or zymosan-activated-serum-induced (ZAS, 10%) filter passage under lipid-free conditions amounted to 61+/-14% and 70+/-13%, respectively. These values decreased with LCT/MCT to 11+/-9% and 15+/-7%; with LCT/MCT-E to 18+/-10% and 28+/-12%; with SL to 39+/-18% and 57+/-14%, and with MCT to 5+/-2% and 10+/-6%, (all P<0.01), while LCT had no effect. Compared to LCT/MCT, the alpha -tocopherol-enriched formulation significantly increased ZAS- and fMLP-induced chemotaxis. fMLP-induced chemotaxis decreased in direct proportion to LCT/MCT triglyceride concentration. Conclusions: Human neutrophil migration is distinctively inhibited by structurally different lipid emulsions, depending on triglyceride chain-length and concentration as well as alpha -tocopherol content.