Effects of particle size on blood clearance and tissue uptake of lipid emulsions with different triglyceride compositions

BACKGROUND: Particle size of IV lipid emulsions affects the catabolism of long-chain triglyceride (LCT) emulsions, but little is known about its effect on the catabolism of medium-chain triglyceride (MCT)- and fish oil (FO)-containing emulsions. METHODS: Large (VLDL size), intermediate, and small (IDL size) emulsions with different triglyceride (TG) compositions were labeled with [3H]cholesteryl oleoyl ether: LCT (triolein 100%), MCT:LCT (trioctanoin:triolein 50%:50%), MCT:LCT:FO (trioctanoin:triolein:triDHA 50%:40%:10%), and FO (triDHA 100%). Emulsions (0.4 mg TG/mouse) were injected into C57BL/6J mice, and blood clearance and tissue uptake of emulsion particles were determined. RESULTS: Large emulsion particles had 2- to 3-fold faster fractional catabolic rates (FCR) compared with small particles with the same TG content. There was 1.5- to 2.0-fold higher FCR of large FO-containing emulsions (FO and MCT:LCT:FO) compared with large LCT and MCT:LCT emulsions, whereas effects of FO on FCR in small emulsions were not observed. Large FO-containing emulsions were taken up more by adipose tissue compared with small particles with concomitant decreases in hepatic uptake. Preinjection of heparin reduced heart and adipose uptakes of FO and MCT:LCT:FO emulsions with increased uptake by liver, suggesting a role of lipoprotein lipase in catabolism of FO-containing emulsions. CONCLUSIONS: In a mouse model, FO addition to large emulsions increased blood clearance and changed organ delivery. In contrast, there was no or little effect when particle size became smaller. We hypothesize that in humans, FO addition to lipid emulsions can help target emulsion delivery to certain extrahepatic tissues, a factor that may be of use for delivering specific fatty acids, or even drugs, to specific organs.     

Lipid and lipid-free total parenteral nutrition: differential effects on macrophage phagocytosis in rats

Lipid emulsions provided with total parenteral nutrition (TPN) have been associated with mononuclear phagocytic system functional changes. The aim of the present investigation was to assess the influence of TPN with added lipid emulsions on macrophage (M phi) phagocytosis. Wistar rats (n = 70) with external jugular vein cannulation were randomized into seven groups. The rats received an oral diet or six different isocaloric (1.16 kcal/mL), isonitrogenous (1.5 g/mL), and isolipidic (30% non-protein calories) TPN regimens: (a) an oral diet with intravenous infusion of saline (OS); (b) non-lipid TPN (glucose); (c) TPN with 10% long chain triacylglycerol emulsions (LCT); (d) TPN with 90% LCT and 10% fish oil (FO) emulsion; (e) TPN with 50% LCT and 50% FO; (f) TPN with 10% lipid emulsion with 50% medium chain triacylglycerol (MCT) and 50% LCT; and (g) TPN with 45% MCT, 45% LCT, and 10% FO. After 96 h of TPN or saline infusion, colloidal carbon (Pelikan, Germany) was injected intravenously at 1.0 mL/kg body weight, and the rats were killed after 3 h. Liver, spleen, and lung were weighed and prepared by immunohistochemistry analyses with the HAM-56 anti-M phi antibody. Under light microscopy, the total M phi number (MT) and the colloidal carbon phagocytic M phi number (MP) were established, and the phagocytic index was calculated as MP/MT x 100. There were no statistical (P < 0.05) differences in liver, spleen, or lung weights among the seven groups in comparison with the OS group. Non-lipid TPN inhibited spleen and lung M phi phagocytosis when compared with the OS and lipid-TPN groups. Lipid TPN supplemented with fish oil emulsion increased total liver and lung M phi number and phagocytosis. These results indicate that TPN supplemented with fish oil increases M phi phagocytosis in rats.     

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.     

Effects of a medium-chain triacylglycerol/long-chain triacylglycerol fat emulsion containing a reduced ratio of phospholipid to triacylglycerol in pediatric surgical patients

OBJECTIVE: Medium-chain triacylglycerol (MCT) has been shown to provide better nutritional support than long-chain triacylglycerol (LCT). We compared the efficacy of MCT/LCT fat emulsions containing a usual (0.12) or a decreased (0.06) ratio of phospholipid to triacylglycerol (PL:TG) in pediatric patients under surgical stress. METHODS: Three patient groups (n=10 in each) received equivalent amounts of glucose (12 g.kg(-1).d(-1)) and amino acids (2 g.kg(-1).d(-1)), but group A received a 10% MCT fat emulsion (PL:TG 0.06), group B received a 20% MCT fat emulsion (PL:TG 0.06), and group C received a 10% MCT/LCT fat emulsion (PL:TG 0.12) in amounts of 1.5 g.kg(-1).d(-1) in a randomized study. Total parenteral nutrition was given for 7 d. Blood samples were collected before total parenteral nutrition administration and on days 4 and 7 for determination of various biochemical indexes. RESULTS: Serum phospholipid concentrations were significantly higher in group C than in group A or B on days 4 and 7 (P<0.05). Serum triacylglycerol and cholesterol concentrations and the very-low-density lipoprotein percentage were also significantly higher in group C than in group A or B on days 4 and 7 (P<0.05). The high-density lipoprotein percentage was significantly higher in group B on days 4 and 7 (P<0.05). CONCLUSIONS: In pediatric patients under surgical stress, a total parenteral nutrition regimen containing an MCT/LCT fat emulsion with a decreased PL:TG ratio (0.06) is likely to result in partly better lipid and lipoprotein metabolism than an emulsion containing the usual ratio (0.12).     

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.     

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.     

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.     

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 providing a restricted amount of linoleic acid in severely burned patients: a randomised double-blind study of an olive oil-based lipid emulsion v. medium/long-chain triacylglycerols

It has been claimed that lipid emulsions with a restricted linoleic acid content can improve the safety of total parenteral nutrition (TPN). The tolerability of TPN and its effects on the metabolism of fatty acids were assessed in this prospective, double-blind, randomised study comparing an olive/soyabean oil long-chain triacylglycerol (LCT) with a medium-chain triacylglycerol (MCT)/LCT; 50:50 (w) based lipid emulsion in two groups (O and M, respectively; eleven per group) of severely burned patients. After resuscitation (48-72 h), patients received TPN providing 147 kJ/kg per d (35 kcal/kg per d) with fat (1.3 g/kg per d) for 6 d Plasma fatty acids, laboratory parameters including liver function tests, and plasma cytokines were assessed before and after TPN. Adverse events encountered during TPN and the clinical outcomes of patients within the subsequent 6 months were recorded. With both lipid emulsions, the conversion of linoleic acid in its higher derivatives (di-homo-gamma-linolenic acid) improved and essential fatty acid deficiency did not appear. Abnormalities of liver function tests occurred more frequently in the M (nine) than in the O (three) group (P = 0.04, Suissa-Shuster test). Seven patients (four from group O and three from group M) died as a consequence of severe sepsis 3-37 d after completion of the 6 d TPN period. When compared with the surviving patients, those who died were older (P = 0.01) and hyperglycaemic at baseline (P < 0.001), and their plasma IL-6 levels continued to increase (P < 0.04). Although fatty acid metabolism and TPN tolerability were similar with both lipid emulsions, the preservation of liver function noted with the use of the olive oil-based lipid emulsions deserves confirmation.     

Tocopherol isoforms in parenteral lipid emulsions and neutrophil activation

BACKGROUND AND AIMS: Tocopherol is a lipid-soluble anti-oxidant that exists in several isoforms. Patients on total parenteral nutrition depend on lipid emulsions for their tocopherol intake. In the present study, we analysed the content of tocopherol isoforms in various lipid emulsions. We also tested the hypothesis that immune-modulating effects of lipid emulsions could be attributed to different concentrations of alpha-tocopherol (alpha-toc) or peroxidation products. METHOD: alpha-, beta-, gamma- and delta-toc were measured in emulsions containing long-chain triglycerides (LCT), mixed long- and medium-chain triglycerides (LCT/MCT), structured lipids (SL), olive oil (OO) or fish oil (FO). As a measure for cellular activation, neutrophil membrane adhesion markers were assessed after exposure to two LCT/MCT emulsions that differ only in alpha-toc content. RESULTS: Various emulsions differed widely in tocopherol contents, especially with respect to the alpha- isoform. The latter isomer also was subject to considerable degradation despite adequate storage conditions. The previously observed activation of neutrophils by LCT/MCT was not influenced by the increased concentration of alpha-toc or the decreased concentration of lipid peroxidation products in a new LCT/MCT emulsion. CONCLUSIONS: Tocopherol supplementation by parenteral lipid emulsions strongly depends on the lipid source and the storage lifetime of the emulsion. The effects of LCT/MCT on the immune system are not modulated by alpha-toc or by lipid peroxidation products.     

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.     

Fatty acid composition of adipocyte membrane phospholipids and stored triglycerides in infants receiving total parenteral nutrition

Fatty acid (FA) composition of membrane phospholipids (PL) and stored triglycerides (TG) from adipose tissue was studied in eight infants aged 1 to 4 months receiving total parenteral nutrition (TPN) since birth. During this period, essential fatty acid (EFA) intake consisted exclusively of soybean oil emulsion administered by intravenous route (Intralipid 20%) representing 301 +/- 88 mg/kg/24 hr of linoleic acid and 58 +/- 18 mg/kg/24 hr of alpha-linolenic acid, or 2.3 +/- 0.6% and 0.4 +/- 0.1%, respectively, of total energy intake. The results were compared with those of eight control infants of the same age receiving orally a normal milk diet with an intake of 660 +/- 260 mg/kg/24 hr of linoleic acid and 101 +/- 35 mg/kg/24 hr of alpha-linolenic acid, or 4.5 +/- 0.7% and 0.7 +/- 0.3%, respectively, of total energy intake. Although their EFA intake was significantly lower (p less than 0.01) and administered only parenterally, after 1 to 4 months the infants receiving TPN still had a membrane phospholipid FA pattern of adipose tissue which was not significantly different from that of normal children of the same age. In stored adipocyte TG, the percentage of linoleic acid was significantly lower (p less than 0.01) in infants receiving TPN. This is probably of nutritional importance as at this stage of life the child builds up its stores of EFA. The proportion of the other fatty acids in adipocyte TG was not significantly modified.     

Antioxidant status of surgical patients receiving TPN with an omega-3-fatty acid-containing lipid emulsion supplemented with alpha-tocopherol

BACKGROUND: LCT lipid emulsions and even more fish oil-containing lipid emulsions are under debate regarding their tocopherol and PUFA content as well as their effect on the antioxidative status especially in patients with oxidative stress. METHODS: Thirty-three patients undergoing major abdominal surgery were randomly assigned to receive either an alpha-tocopherol-supplemented (562 micromol/l) MCT/LCT/omega-3-acid triglycerides (MLF, 5/4/1 w/w/w, 20%) emulsion or a soybean oil-based LCT emulsion (20%). The TPN regimen continuously provided 1.4 g fat kg bw(-1)d(-1)over 5 days. RESULTS: Plasma antioxidant concentrations were strongly reduced by surgical treatment. Following 5 days of TPN with the MLF emulsion, mean plasma alpha-tocopherol increased by 20.0 micromol/l (1.98 micromol/mmol lipid), while nearly no change was observed in the LCT emulsion group. In both groups, plasma concentrations of all non-supplemented antioxidants (vitamin C, carotenoids, selenium) as well as serum total antioxidant capacity further decreased during TPN. The concentrations of plasma cholesterol oxidation products as a measure of in vivo lipid peroxidation revealed no changes over the TPN period in either group. CONCLUSION: In contrast to the LCT emulsion, administration of the a-tocopherol supplemented MLF lipid emulsion normalized a-tocopherol plasma concentrations. Despite its high long-chain PUFA content, no hint for increased lipid peroxidation was found.     

A metabolic comparison of a pure long-chain triglyceride lipid emulsion (LCT) and various medium-chain triglyceride (MCT)-LCT combination emulsions in dogs

Two 20% lipid emulsions containing mixtures of long-(LCT) and medium-chain triglycerides (MCT) were compared with a 20% LCT lipid emulsion. Beagles were infused with emulsions containing either 100% LCT, 75% LCT-25% MCT, or 50% LCT-50% MCT. The emulsions were part of a total parenteral nutrition (TPN) regimen that included 10% dextrose and 5.5% amino acids. Basic nutritional parameters as well as elimination kinetics were monitored. Plasma linoleic acid, ketone, lactate, pyruvate, insulin, glucose, and carnitine were analyzed. The 75% LCT-25% MCT emulsion offers little advantage over 100% LCT as a metabolic substrate. The 50% LCT-50% MCT combination proved to be a potentially better caloric source due to rapid elimination kinetics, increased ketone production, lack of deposition, and no interference with linoleic acid metabolism.     

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.     

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.     

脂肪乳的特点及临床应用

脂肪乳剂是构成TPN中非蛋白质能量的来源之一。传统的以大豆油为基础的长链脂肪乳,由于长链脂肪乳存在导致脂质过氧化、免疫抑制、诱发炎症和损伤内皮系统作用的潜在风险,因此,研究出了中／长链脂肪乳剂、鱼油、橄榄油、结构脂肪乳剂、SMOF等。不同脂肪乳剂的差别主要在于甘油三酯的不同,即结合于甘油的脂肪酸的不同,而脂肪酸的不同代谢特点决定了各种脂肪乳剂在临床中的不同应用。     

Effect of Medium-Chain Triglyceride Emulsion in Total Parenteral Nutrition on Experimental Hepatic Metastasis in the Rat

Background: This study evaluated the effect of total parenteral nutrition (TPN) regimens containing a medium-chain triglyceride (MCT) emulsion on tumor metastasis. Methods: Tumor metastasis development was assessed by the number of metastatic foci on the liver surface in rats inoculated with ACL-15 tumor cells via the portal vein. Rats received one of the following TPN regimens: TPN containing an MCT emulsion (group M), in which tricaprylin emulsion served as the MCT and comprised 50% of nonprotein calories (NPC); TPN containing a long-chain triglyceride (LCT) emulsion (group L), in which soybean oil served as the LCT and comprised 50% of NPC; and TPN without lipid emulsion (group G), in which dextrose comprised 100% of NPC. Results: The number of metastatic foci was greatest in rats receiving TPN containing the MCT emulsion on day 11 after tumor cell inoculation and either 11 days of TPN or 2 days of TPN followed by 9 days standard rat chow. Conclusions: TPN containing MCT emulsion increases liver metastasis early in its administration. (Journal of Parenteral and Enteral Nutrition 21:220–223, 1997)     

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.     

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.