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)     

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.     

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.     

Effect of various lipid emulsions on total parenteral nutrition-induced hepatosteatosis in rats

The effect of various lipid emulsions on the development of fatty liver during total parenteral nutrition (TPN) was investigated in rats given TPN for 7 days. Medium-chain triglycerides (MCT), long-chain triglycerides (LCT), chemically defined triglycerides (CDT; structured lipid with a high purity of 94.3%), and a mixture of MCT and LCT (MIX) were prepared as the lipid emulsions. TPN provided 350 kcal/kg/day, with a nonprotein calorie/nitrogen ratio of 160. The TPN-1 group received 10% nonprotein calories and the TPN-2 group received 30% nonprotein calories. MCT TPN was found to have some disadvantages, especially with regard to nitrogen balance and plasma albumin levels. Total cholesterol and phospholipids tended to be high in the MCT TPN group. The hepatic lipid content was higher in the lipid-free TPN and the MCT TPN groups, and lower in the CDT and LCT TPN groups. Histologically, the livers of the MIX, CDT, and LCT TPN groups showed less fatty change than those of the FREE and MCT groups.     

Arterial deepvenous difference of lipoproteins in skeletal muscle of patients in postoperative state: effects of medium chain triglyceride emulsion

The effect of fat infusion with medium chain triglycerides (MCT) and long chain triglycerides (LCT) on serum lipoproteins before and after passage through the skeletal muscle was investigated with the forearm technic in eight patients after abdominal operation. All lipoprotein fractions were enriched with triglycerides and phospholipids from infused artificial fat particles with the consequence of significantly increased ratios of TG/PL and TG/apo B in VLDL, of TG/apo B in LDL and TG/apo A-I in HDL. Uptake and release of lipoprotein components by skeletal muscle are given by arterial-deepvenous differences considering the blood flow rates. The positive arterial-deepvenous difference of VLDL triglycerides after 4-hr infusion is interpreted as cleavage and uptake of infused MCT by the muscle. The release of LDL is more pronounced after the fat infusion than before, suggesting a degradation and enhanced catabolism of artificial fat particles. HDL release may be also a consequence of catabolism of artificial TG/PL-particles. These results indicate an uptake of MCT/LCT emulsion by the skeletal muscle.     

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.     

Parenteral nutrition using MCT/LCT or LCT: Effect on the fatty acid composition of plasma triglycerides and platelet phospholipids

Plasma triglyceride fatty acids and platelet phospholipid fatty acids were compared in 20 malnourished patients before and after 8-10 days of total parenteral nutrition which included either a conventional lipid emulsion (LCT) or a new emulsion containing medium chain triglyercides (MCT/LCT). The use of both lipid emulsions altered the fatty acid profiles. The percentage of linoleic acid in the plasma triglycerides increased with both lipid emulsions, but more markedly with LCT. The median percentage after LCT was 25.9 (range 16.9-31.5) which was significantly higher (p < 0.01) than after MCT/LCT - 14.8 (range 6.1-20.2), or in healthy volunteers. After 8-10 days on MCT/LCT the fatty acid profile retained some features of the malnourished state, despite correction of the linoleic acid content. The percentage of linolenic and arachidonic acid in the platelet phospholipids tended to be lower than after LCT use, and the percentage of linoleic acid was significantly less (p < 0.01), the median (range) being 8.2 (4.5-23.8) after MCT/LCT and 11.7 (4.8-16.0) on LCT. Short term use of MCT/LCT emulsion may correct the fatty acid changes of malnutrition rather more slowly and results in a different fatty acid profile to that seen after LCT use. Whether this has any clinical effects is unclear.     

Effects of 2 lipid emulsions (LCT versus MCT/LCT) on the fatty acid composition of plasma phospholipid: a double-blind randomized trial

BACKGROUND: Fatty acids from the diet or from IV fat emulsions are incorporated into the plasma and cell membrane phospholipids and act as substrates in the synthesis of eicosanoids. This study reports the effect of 2 parenteral lipid emulsions in plasma phospholipids fatty acids. METHODS: A total of 83 patients aged 18 to 75 years were randomized to receive long-chain triglycerides (LCT) or 50/50 mix of long- and medium-chain triglyceride emulsion (LCT/MCT). Blood samples were collected at baseline and at weekly intervals for 28 days. Plasma phospholipid fatty acids were measured by gas chromatography. RESULTS: Patients receiving LCT versus MCT/LCT emulsion have an increase in 18:2n6 and a decrease in 20:4n6 and 22:4n6 after 7, 14, and 21 days of treatment with parenteral nutrition. Phospholipid fatty acids at 15 days of treatment with parenteral nutrition with LCT versus MCT/LCT for 18:2n6 were 17.30% versus 22,90% (p < .05), for 20:4n6 10.44% versus 8.38% (p < .05), and for 22:4n6 0.51% versus 0.40% (p < .05). The 20:4n6 percentage inversely correlated with the percentage of 18:2n6 on days 7, 14, and 21: regression coefficients: -7.40 (p < .001), -7.39 (p < .001), and 5.70 (p < .001), respectively. CONCLUSIONS: Parenteral lipid emulsions modify fatty acid profiles in plasma phospholipids. MCT/LCT emulsions produce in phospholipids a fatty-acid profile that is closer to normality than that achieved with LCT emulsions. These changes in phospholipid fatty acids are suggestive of an inhibition of A-5-desaturase in patients who received LCT emulsions.     

Comparison of metabolic clearance rates of MCT/LCT and LCT emulsions in diabetics

In seven moderately overweight noninsulin-dependent diabetics with slightly elevated triglyceride levels, disappearance rates of infused medium chain triglyceride/long chain triglyceride (MCT/LCT) and long chain triglyceride (LCT) emulsions were compared. Five metabolically healthy volunteers served as controls. During a 3-hr lipid infusion, serum triglycerides reached a steady state with both emulsions in the healthy controls, whereas, in diabetic patients, steady state triglyceride levels were seen only with MCT/LCT. After the end of the lipid infusion, the longest half-life value in the decline of triglyceride levels was found with LCT in diabetics, whereas significantly shorter and quite similar half-life values were found with LCT in healthy controls and with MCT/LCT in diabetics. As expected, the shortest half-life for serum triglycerides was found in healthy controls after MCT/LCT-infusion. Virtually the same differences in serum concentrations and in half-life times were seen with free fatty acids. According to these data, if needed, parenteral nutrition with lipids in states of disturbed glucose and lipid metabolism may preferentially be done with MCT/LCT emulsions.     

Randomized Clinical Trial of New Intravenous Lipid (SMOFlipid 20%) Versus Medium‐Chain Triglycerides/Long‐Chain Triglycerides in Adult Patients Undergoing Gastrointestinal Surgery

Background: SMOFlipid 20% is intravenous lipid emulsion (ILE) containing long‐chain triglycerides (LCT), medium‐chain triglycerides (MCT), olive oil, and fish oil as a mixed emulsion containing α‐tocopherol. The aim was to assess the efficacy of this new ILE in gastrointestinal surgery compared with MCT/LCT. Methods: In this prospective study, 40 patients were randomized to SMOFlipid 20% or MCT/LCT (Lipovenoes 20%) group. Clinical and biochemistry data were collected. Inflammatory markers (CRP, IL‐6, IL‐10, TNF‐α, TGF‐β1) and oxidative stress (ROS and superoxide) were measured. Results: Thirty‐five patients (17 males and 18 females) with a mean age of 57 years completed the study. The patients’ demographic characteristics (age, gender, height, body weight, and BMI) were similar without significant differences between groups. The increment of triglyceride on day 6 from baseline was significantly lower in SMOFlipid group than in Lipovenoes MCT/LCT group. Inflammatory markers, as well as superoxide radical and total oxygen radical were not different between groups. Conclusions: Despite the comparable effect on inflammatory response, because of its well‐balanced fatty acid pattern, relatively low n‐6:n‐3 ratio, and high vitamin E content, SMOFlipid had a better triglyceride‐lowering effect as compared with MCT/LCT in adult patients undergoing gastrointestinal surgery.     

Total parental nutrition using conventional and medium chain triglycerides: effect on liver function tests, complement, and nitrogen balance

Conventional long chain triglyceride (LCT) was compared with a new emulsion containing 50% medium chain triglyceride (5% MCT/5% LCT) in a randomized cross-over trial of 10 days duration. Plasma concentrations of albumin, prealbumin, the complement components C3 and C4, and prothrombin times measured daily at 8 am, before lipid infusion, showed no progressive change during the 10 days of the trial, nor in each separate 5-day period when LCT or MCT/LCT was infused. Aspartate transaminase and alkaline phosphatase activities were similar over the two periods. There was a significant increase (compared with preinfusion levels) in C3 and C4 levels after 5 hr of either lipid infusion. Nitrogen balance was improved, and plasma bilirubin levels were lower on the regimen containing MCT/LCT.     

MCT/LCT emulsion ameliorate liver fat deposition in insulin-treated diabetic rats receiving total parenteral nutrition

This study was designed to investigate the effects of high energy infusion and insulin treatment on plasma and liver lipids in diabetic rats receiving total parenteral nutrition (TPN). Diabetes was induced in rats by streptozotocin. The diabetic rats were assigned to two TPN groups to receive either long chain triglyceride (LCT) or medium chain triglyceride (MCT)/LCT (1:1) as a fat source. The TPN solutions were isonitrogenous, isocaloric and identical in nutrient composition except for the fat emulsion. All rats received the TPN solution at an energy level of 35|kcal/100|g of body weight. The LCT and MCT/LCT groups were further divided into two subgroups, depending on whether they were treated with insulin. The results demonstrated that, between the MCT/LCT and LCT groups, no differences were observed in body weight and nitrogen retention, as well as the concentrations of plasma glucose, nonesterified fatty acids, beta-hydroxybutyrate, and total cholesterol. Diabetic TPN rats without insulin treatment had weight loss and negative nitrogen balance during the experiment. Diabetic TPN rats treated with insulin, however, demonstrated less weight loss and positive nitrogen retention. Insulin treated groups had significantly higher liver fat content than did those without insulin treatment. Furthermore, liver fat content was significantly higher in the LCT group than in the MCT/LCT group among insulin treated TPN rats. These results suggest that compared with the LCT emulsion, infusion of the MCT/LCT emulsion ameliorated liver fat deposition in insulin-treated diabetic rats receiving TPN.     

糖尿病患者中链和长链甘油三酯乳剂的清除比较

比较胰岛素非依赖性糖尿病患者中/长链甘油三酯(MCT/LCT)混合乳剂和长链甘油三酯(LCT)乳剂的清除率。每组各6例,在4小时输入脂肪期间,MCT/LCT组血甘油三酯达稳定状态。动力学参数表明MCT/LCT乳剂有着明显较小的表观分布容积和较短的半衰期。两种乳剂对血糖浓度也有不同的影响。在葡萄糖和脂肪代谢紊乱时,如需行含脂肪的肠外营养,应优先选择MCT/LCT混合乳剂。     

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.     

Effects of intravenous supplementation with alpha-tocopherol in patients receiving total parenteral nutrition containing medium- and long-chain triglycerides

OBJECTIVE: To compare the effects of a lipid emulsion containing medium-chain triglycerides (MCT) and supplemented with alpha-tocopherol to a conventional long-chain triglyceride (LCT) emulsion. DESIGN: Randomised double blind study. SETTING: Department of Internal Medicine, Antwerp University Hospital. SUBJECTS AND INTERVENTIONS: Twenty-four patients with an indication for total parenteral nutrition for a minimum of 10 days were randomly assigned to two groups: group E received as lipid source MCT/LCT (50/50) suplemented with 100 mg DL-alpha-tocopherol/day and group C received LCT. Blood samples were analysed at inclusion, after 4-6 and after 9-11 days. RESULTS: In group E, serum alpha-tocopherol doubled from 11.4+/-6.9 at inclusion to 20.9+/-7.9 and to 23.8+/-8.8 microg/ml after 4 and 9 days, respectively, but did not change in group C (P=0.008). Production of thiobarbituric acid-reacting substances (TBARS) after 120 min incubation with copper decreased from 66+/-34 at inclusion to 29+/-25 nmol MDA/mg LDL and VLDL-cholesterol after 4 and to 42+/-17 after 9 days (P=0.022 when compared to group C, which underwent no significant changes). Velocity of production of fluorescent products decreased in group E but not in group C (P=0.026). CONCLUSIONS: Supplementation of TPN containing MCT/LCT with 100 mg DL-alpha-tocopherol/day leads to a doubling in serum alpha-tocopherol and to a decrease in the susceptibility of LDL and VLDL to peroxidation in vitro. SPONSORSHIP: This study was partly financed by B Braun Medical NVSA, Diegem, Belgium.     

Short-term effects of parenteral nutrition of cholestatic infants with lipid emulsions based on medium-chain and long-chain triacylglycerols

OBJECTIVE: Infants with chronic cholestasis may require parenteral nutrition with lipid emulsions to provide energy and essential fatty acids but the optimal strategy is controversial. METHODS: We studied the effects of parenteral lipid emulsions with long-chain triacylglycerols (LCTs) or a mixture of LCTs and medium-chain triacylglycerols (MCTs/LCTs) on serum bilirubin and lipid metabolism in cholestatic infants who received these 20% emulsions in alternating order for 3 d each, together with a glucose and amino acid infusion. RESULTS: Of 11 recruited infants, two dropped out because enteral feeding could be established. In nine infants (2-8 mo of age, mean age 4.2 mo) who completed the study, serum bilirubin decreased from baseline to 6 h after the end of LCT infusion (from 8.5 +/- 2.0 to 7.8 +/- 1.8 mg/dL, mean +/- SEM, P < 0.05) and MCT/LCT infusion (7.9 +/- 6.5 to 7.1 +/- 6.5 mg/dL, P < 0.05). Cholesterol, triacylglycerol, and phospholipid concentrations in plasma and in chylomicrons, very low-density lipoprotein, low-density lipoprotein, and high-density lipoprotein were not changed by either emulsion. Total polyunsaturated fatty acid contents in high-density lipoprotein phospholipids increased during LCT infusion (from 29.8 +/- 0.9 to 35.9 +/- 1.4% wt/wt, P < 0.05) and MCT/LCT infusion (from 30.4 +/- 1.0 to 33.0 +/- 0.7%, P < 0.05). The long-chain polyunsaturated fatty acid docosahexaenoic acid increased only with the LCT infusion. Because docosahexaenoic acid availability during infancy is important for early visual and cognitive development, the use of soybean oil-based lipid emulsions may be preferable for infants with severe progressive cholestasis. CONCLUSION: The MCT/LCT and LCT emulsions showed a good metabolic tolerance in infants with chronic cholestasis but had a differential effect on high-density lipoprotein phospholipid contents of arachidonic and docosahexaenoic acids.     

Nitrogen sparing effect of structured triglycerides containing both medium-and long-chain fatty acids in critically ill patients; a double blind randomized controlled trial

BACKGROUND AND AIMS: Patients with sepsis and trauma are characterised by hypermetabolism, insulin resistance and protein catabolism. Fat emulsions containing medium chain triglycerides have been suggested to be beneficial for these patients since medium chain fatty acids are a more readily available source of energy when compared to long chain fatty acids. The aim of this study was to compare a medium and long chain triglyceride emulsion consisting of structured triglycerides (ST) with a long chain triglyceride (LCT) emulsion in terms of effects on nitrogen balance, energy metabolism and safety. METHODS: 30 ICU patients with sepsis or multiple injury received a fat emulsion with ST or 20% LCT (1.5 g triglycerides/kg body weight/day) as a component of total parenteral nutrition (TPN), for 5 days in a double blind randomised parallel group design. The main analysis was made on the 3 day per protocol population due to lack of patients at day 5. RESULTS: There were no differences in baseline characteristics of the two groups receiving either the LCT or the ST emulsion. The efficacy analysis was performed on the per protocol population (n=9 ST, n=11 LCT). There was a significant difference between the two treatments regarding daily nitrogen balances when the first 3 days were analysed P=0.0038). This resulted in an amelioration of the nitrogen balance on day 3 in the group on ST as compared to those on LCT (0.1+/-2.4 g vs -9.9+/-2.1 g P=0.01). The 3 day cumulative nitrogen balance was significantly better in the group receiving ST compared to those on LCT (-0.7+/-6.0 vs -16.7+/-3.9 P=0.03). This better cumulative nitrogen balance on day 3 was also preserved as a tendency (P=0.061) in the analysis of the intention to treat population, but on day 5 there was no significant difference (P=0.08). The ST emulsion was well tolerated and no difference was found compared to the LCT emulsion regarding respiratory quotient, energy expenditure, glucose or triglyceride levels during infusion. CONCLUSION: Administration of a structured triglyceride emulsion resulted in an amelioration of nitrogen balance despite no effect on energy expenditure in short term administration over 3 days to ICU patients when compared to a long chain triglyceride emulsion. No side effects linked to medium chain triglycerides were noted.     

Triglycerides in fish oil affect the blood clearance of lipid emulsions containing long- and medium-chain triglycerides in mice

Lipid emulsions containing long-chain triglycerides (LCT) and medium chain triglycerides (MCT) are widely used in parenteral nutrition. Recently, fish oil (FO) triglyceride (TG)-derived emulsions are considered therapeutic because of their many beneficial biological modulatory actions. We investigated in mice whether adding 10% FO to an intravenous lipid emulsion with MCT and LCT (MCT:LCT:FO -50:40:10% by wt) would affect particle blood clearance and tissue targeting in comparison to LCT (100% by wt) and MCT:LCT (50:50% by wt) emulsions. The 3 emulsions were labeled with [3H] cholesteryl oleoyl ether and administered by bolus injection (400 microg TG/mouse) to C57BL/6J mice. Contributions of LDL receptor (LDL-R) and LDL-R-related protein to emulsion catabolism were assessed using LDL-R-deficient mice and preinjection of lactoferrin, and the effects of lipoprotein lipase (LPL) were determined by preinjection of heparin and Triton WR 1339. Although fractional catabolic rates did not differ among the 3 emulsions, blood removal at each time point after injection was greater for MCT:LCT:FO particles due to their higher initial margination volume. Compared with MCT:LCT and LCT emulsions, patterns of tissue uptake of the MCT:LCT:FO emulsions were different, e.g. MCT:LCT:FO emulsion particle uptake was lower in heart, adipose tissue, and muscle, and higher in lung, and the removal of MCT:LCT:FO emulsion particles was less dependent on LPL, LDL-R, and lactoferrin-sensitive pathways. These data suggest that the addition of a low percentage of FO to MCT:LCT emulsions substantially changes their particle clearance and tissue uptake mechanisms.     

Medium-chain, triglyceride-containing lipid emulsions increase human neutrophil beta2 integrin expression, adhesion, and degranulation

BACKGROUND: To test the hypothesis that lipid emulsions with different triglyceride structures have distinct immunomodulatory properties, we analyzed human neutrophil adhesion and degranulation after lipid incubation. METHODS: Neutrophils, isolated from the blood of 10 healthy volunteers, were incubated in medium or physiologic (2.5 mmol/L) emulsions containing long-chain (LCT), medium-chain (MCT), mixed LCT/MCT, or structured (SL) triglycerides. Expression of adhesion molecules and degranulation markers was evaluated by flow cytometry. Also, functional adhesion was investigated by means of a flow cytometric assay using fluorescent beads coated with the integrin ligand intercellular adhesion molecule (ICAM)-1. RESULTS: Although LCT and SL had no effect, LCT/MCT significantly increased expression of the beta2 integrins lymphocyte-function-associated antigen 1 (+18%), macrophage antigen 1 (+387%), p150,95 (+82%), and (alphaDbeta2 (+230%). Degranulation marker expression for azurophilic (CD63, +210%) and specific granules (CD66b, +370%) also significantly increased, whereas L-selectin (CD62L, -70%) decreased. The effects of LCT/MCT were mimicked by the MCT emulsion. ICAM-1 adhesion (% beads bound) was increased by LCT/MCT (34% +/- 4%), whereas LCT (19% +/-3%) and SL (20% +/- 2%) had no effect compared with medium (17% +/- 3%). CONCLUSIONS: LCT/MCT and MCT, contrary to LCT and SL emulsions, increased neutrophil beta2 integrin expression, adhesion, and degranulation. Apart from other emulsion constituents, triglyceride chain length might therefore be a key feature in the interaction of lipid emulsions and the phagocyte immune system.     

Parenteral infusion of long- and medium-chain triglycerides and reticuloendothelial system function in man

Previous study demonstrated that patients who received total parenteral nutrition (TPN) with standard intermittent infusion of long chain triglyceride (LCT) at 0.13 g kg-1hr-1 over 10 hr for each of three days showed a significant decline in 99Tc-sulfur colloid (TSC) clearance rate by the reticuloendothelial system (RES). The present studies evaluated eight patients who received the same total lipid dose of LCT infused continuously as in a three-in-one admixture, and another nine patients receiving the same amount of fat as a medium chain triglyceride (MCT)/LCT (75%/25%) emulsion intermittently over 10 hr at 0.13 g kg-1hr-1 for three consecutive days. Patients were given continuous total parenteral nutrition (TPN) comprised of protein, 1.5 g kg-1day-1, and dextrose, 4.5 g kg-1day-1. RES function was examined by measuring the clearance rates of intravenously injected TSC while receiving TPN containing only protein and dextrose, and again after three days of fat infusion. Mean (+/- SEM) clearance rate constants before and after continuous LCT infusion were 0.38 +/- 0.09 and 0.41 +/- 0.08 min-1, respectively, while those before and after intermittent MCT/LCT infusion were 0.50 +/- 0.18 and 0.73 +/- 0.24 min-1, respectively. In contrast to intermittent LCT infusion, the administration of continuous LCT or an intermittent MCT/LCT mixture does not impair TSC clearance by the RES. These findings suggest that condensing the daily period of LCT infusion at standard dosage may exceed the rate of metabolic utilization, resulting in increased fat removal and diminished TSC uptake by the RES.(ABSTRACT TRUNCATED AT 250 WORDS)