Blood clearance kinetics and organ delivery of medium-chain triglyceride and fish oil-containing lipid emulsions: Comparing different animal species.

BACKGROUND & AIMS: Medium-chain triglycerides (TG) (MCT) and fish oil (FO) TG are incorporated as the core TG component into intravenous (IV) lipid emulsions for infusion in parenteral nutrition. Bolus injections of IV emulsions, on the other hand, have emerged as a novel therapeutic approach to treat various acute disorders. However, intravascular metabolism and organ delivery of acute IV injection of emulsions containing both MCT and FO are not fully defined, nor have they been characterized across common experimental animal models. We characterized and compared blood clearance kinetics and organ distribution of bolus injections of MCT/FO emulsions among different animal species. We also examined whether sex differences or feeding status can affect catabolic properties of MCT/FO lipid emulsions. DESIGN: Blood clearance rates of lipid emulsions with specific TG composition were compared in rats IV injected with [3H]cholesteryl hexadecyl ether labeled pure n-6 long-chain (LCT) and n-3 FO TG lipid emulsions, or emulsions containing MCT and FO at different ratios (wt/wt), which include 8:2 (80% MCT: 20% FO), 5:4:1 (50% MCT: 40% LCT: 10% FO) and SMOF (30% LCT: 30% MCT: 25% olive oil: 10% FO). Dose-response effects (0.016 mg-1.6 mg TG/g body weight) of the MCT/FO 8:2 emulsions on blood clearance properties and organ delivery were determined in both mice and rats. Blood clearance kinetics and organ uptake of MCT/FO 8:2 emulsions were compared between male and female rats and between fed and fasted rats. Changes in plasma lipid profiles after acute injections of MCT/FO 8:2 lipid emulsion at different doses (0.043, 0.133, and 0.4 mg TG/g body weight) were characterized in non-human primates (Cynomolgus monkeys). RESULTS: MCT/FO 8:2 emulsion was cleared faster in rats when compared with other emulsions with different TG contents. Mice had faster blood clearance and higher fractional catabolic rates (FCR) when compared with the rats injected with MCT/FO 8:2 emulsions regardless of the injected doses. Mice and rats had similar plasma TG and free fatty acid (FFA) levels after low- or high-dose injections of the MCT/FO emulsion. Tissue distribution of the MCT/FO 8:2 lipid emulsion are comparable between mice and rats, where liver had the highest uptake per recovered dose among all organs (>60%). Feeding status and sex differences did not alter the blood clearance rate of the MCT/FO 8:2 emulsion in rats. In a nonhuman primate model, dose-response increases in plasma TG and FFA were observed after IV injection of MCT/FO 8:2 emulsions within the 1st 10 min. CONCLUSION: A lipid emulsion containing both MCT and FO TG is cleared rapidly in blood and readily available for organ uptake in rodent and primate animal models. Characterization of the blood clearance properties of the MCT/FO 8:2 emulsion administered in various animal models may provide further insight into the safety and efficacy profiles for future therapeutic use of bolus injections of MCT/FO emulsions in humans.

Rapid enrichment of cell phospholipids in long-chain polyunsaturated ω-3 fatty acids after a bolus intravenous injection of a medium-chain triacylglycerol: fish oil emulsion in humans.

The present review aims at highlighting the use of a recently developed medium-chain triacylglycerol:fish oil (MCT:FO) emulsion for the rapid and sustained enrichment of long-chain polyunsaturated ω-3 fatty acids in cell phospholipids. Preclinical in vitro, in vivo, and ex vivo experiments are briefly considered with emphasis on the changes in the fatty acid pattern of cell phospholipids in several organs, the partial correction of liver steatosis, and the cardiovascular modification of cationic and functional variables observed in ω-3-depleted rats examined 60-120 minutes after a bolus intravenous (IV) injection (1.0 mL) of the MCT:FO emulsion. The clinical findings collected in healthy male volunteers before or after the bolus IV injection (50.0 mL) of either the MCT:FO emulsion or a control medium-chain triacylglycerol:long-chain triacylglycerol emulsion are also reviewed, with emphasis on the rapid (within 60 minutes) and sustained (up to 2-3 days) enrichment of platelet and white blood cell phospholipids in long-chain polyunsaturated ω-3 fatty acids and hemostatic safety of the present procedure proposed as a tool for the rapid prevention or correction of metabolic and functional disturbances in humans with a relative deficiency in such ω-3 fatty acids.

Rapid cellular enrichment of eicosapentaenoate after a single intravenous injection of a novel medium-chain triacylglycerol:fish-oil emulsion in humans.

BACKGROUND: Dietary deficiency in n-3 (omega-3) polyunsaturated fatty acids (PUFAs) prevails in Western populations and potentially results in adverse health outcomes. To circumvent the slow n-3 PUFA incorporation in phospholipids of key cells after oral supplementation, a new preparation for intravenous bolus injection was developed with 20 g triacylglycerols/100 mL of a mixture of 80% medium-chain triacylglycerols (MCTs) and 20% fish oil (FO) (wt:wt), and 0.4 g alpha-tocopherol/100 mL of the same mixture. OBJECTIVE: Our objective was to document the enrichment of n-3 PUFAs in leukocyte and platelet phospholipids after a bolus intravenous injection of MCT:FO in men. DESIGN: Twelve healthy male subjects received injections over a 5-min period of 50 mL of either MCT:FO or a control MCT:long-chain triacylglycerol (MCT:LCT) emulsion containing 20 g triacylglycerols/100 mL with equal amounts (wt:wt) of MCT and soybean triacylglycerols (LCT) and containing 0.02 g alpha-tocopherol/100 mL; after an 8-wk interval, the subjects received injections of the other preparation. RESULTS: Clinical and biological variables that assessed tolerance and safety remained unchanged. Plasma elimination was faster for MCT:FO than for MCT:LCT (half-life: 24.5 +/- 3.5 min compared with 32.9 +/- 3.0 min; P < 0.025). This was associated with a greater increase in the plasma nonesterified fatty acid concentration. The content of n-3 PUFAs, specifically eicosapentaenoic acid (20:5n-3), increased in leukocyte and platelet phospholipids within 60 min and > or =24 h after MCT:FO injection. CONCLUSION: Bolus intravenous injection of a novel MCT:FO emulsion allows rapid enrichment of cells with n-3 PUFAs.

Alteration of lipid fatty acid profile and cationic fluxes in ventricular cardiomyocytes from omega3-depleted rats.

The bolus intravenous injection of a medium-chain triglyceride:fish oil emulsion was recently found to increase within 60 min the cell phospholipid content in long-chain polyunsaturated omega3 fatty acids and, hence, proposed as a potential tool to prevent cardiac arrhythmia in subjects with a decreased dietary intake of such fatty acids. In the present study, ventricular cardiomyocytes from second generation rats depleted in omega3 fatty acids were found to display the same changes in the phospholipid fatty acid pattern as that previously documented in the cardiac muscle and endothelium of such rats, altered 86Rb and 45Ca fluxes with emphasis on a decrease in both K+ inflow and K+ content and an increase in both Ca2+ inflow and content. The alteration of K+ inflow could not be attributed to a decrease in ouabain-sensitive Na+,K+-ATPase activity as measured in cell homogenates. The cationic alterations were corrected, in part at least, by the prior intravenous injection of the medium-chain triglyceride:fish oil emulsion 60 min before sacrifice of the omega3-depleted rats.

Effect of ALA-enriched food supply on cardiovascular risk factors in males.

The outcome of a total dietary approach using a wide range of n-3 polyunsaturated fatty acids (PUFA) enriched food items on cardiovascular diseases called for further investigation. The study objective was to assess the effect of an ALA-enriched food supply on cardiovascular risk factors in healthy males. A dietary intervention (single-blind field trial with pre- and post-measurements) was performed with 59 healthy males in a Belgian prison. Over a period of 12 weeks they were supplied with an n-3 enriched diet (containing 6.5 g n-3 PUFA/day compared to 4 g n-3 PUFA/day in the standard diet) that was substituted for their regular diet, increasing mainly the alpha-linolenic acid intake (from 2.8 to around 5 g/day). The results indicated no impact on subjects waist circumference, weight and BMI or systolic blood pressure. In contrast, the diastolic blood pressure significantly decreased during the intervention period (from 74.6 +/- 8.2 to 71.7 +/- 10.1 mmHg; P < 0.02). Moreover, the HDL-cholesterol level increased in non-smoking participants (from 0.97 +/- 0.25 to 1.06 +/- 0.23 mmol/l; P < 0.03). In summary, the study demonstrated that enrichment of commonly eaten food items with n-3 fatty acids provides the opportunity to increase the n-3 fatty acid intake and to decrease the n-6/n-3 ratio which results in a decreasing diastolic blood pressure and an increase of HDL-cholesterol (in non-smokers).

Vitamin D deficiency and hyperparathyroidism in relation to ethnicity: a cross-sectional survey in healthy adults.

BACKGROUND: The study of vitamin D status at population level gained relevance since vitamin D deficiency was recently suggested to trigger chronic disease. AIM OF THE STUDY: We aimed to describe vitamin D status, its association with bone and mineral metabolism and risk factors for deficiency in adults over 40 years in Belgium. METHODS: We conducted a cross-sectional survey in a stratified random sample of 401 subjects aged between 40 and 60 years living in Brussels, and drawn from 4 different ethnic backgrounds: autochthonous Belgian, Moroccan, Turkish and Congolese. 25-Hydroxyvitamin D (25OHD), parathyroid hormone (PTH), osteocalcin, C-telopeptide and bone mineral density was measured. RESULTS: Three-hundred and six subjects (77%) showed 25OHD concentrations below 50 nmol/l,135 (34%) below 25 nmol/l and 18 (5%) below 12.5 nmol/l. The proportion of subjects with vitamin D deficiency was four times greater amongst those of Moroccan or Turkish descent compared with those of Congolese or Belgian descent. Moroccan subjects showed a significant higher PTH and bone marker concentrations compared to Belgian. Ethnicity, season and sex were independently associated with vitamin D deficiency in multivariate analysis. CONCLUSION: The prevalence of vitamin D deficiency is very high amongst the adult population of Brussels but immigrants are at greater risk. Given the established link between population health and adequate vitamin D status, a policy of vitamin D supplementation should be considered in these risk groups.

Hemostatic safety of the bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion.

The bolus intravenous injection of a novel 8:2 medium-chain triglyceride:fish oil emulsion was recently found to increase within 60 min and for the subsequent 24-48 h the long-chain polyunsaturated omega3 fatty acid content of both leucocyte and platelet phospholipids in 12 normal subjects. The aim of the present report is to document the hemostatic safety of such a procedure in the same 12 subjects. No adverse effect was found when comparing the results obtained after administration of either the fish oil-containing emulsion or a control 5:5 medium-chain triglyceride:soybean triglyceride emulsion, whether in terms of the occlusion time in either an ADP or epinephrine test or in terms of the [CD]42b, [CD]62p, fibrinogen and PAC-1 response to ADP, collagen or thrombin receptor analog peptide 6 in platelets examined by fluorescence activated cell sorting. In conclusion, this novel procedure for the rapid enrichment of cell phospholipid in long-chain polyunsaturated omega3 fatty acids presents the required safety in a hemostatic perspective.

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.

Preferential enrichment of liver phospholipids in docosahexaenoate relative to eicosapentaenoate in omega-3-depleted rats injected with a medium-chain triglyceride: fish oil emulsion.

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil (FO) emulsion was recently proposed as a tool to provoke a rapid enrichment of cell phospholipids in long-chain polyunsaturated omega-3 fatty acids. In the present study, the enrichment of liver phospholipids and triglycerides in C20:5omega-3, C22:5omega-3 and C22:6omega-3 was assessed 60min after the intravenous administration of FO (1.0ml) to second-generation omega-3-depleted rats. When compared to uninjected rats, or animals injected with a control omega-3 fatty acid-poor medium-chain triglyceride:olive oil (OO) emulsion, the enrichment of liver phospholipids, and to a lesser extent liver triglycerides, attributable to the injection of the FO emulsion was more pronounced for C22:6omega-3 than C20:5omega-3, despite the presence of equal amounts of these two omega-3 fatty acids in the injected diglycerides and triglycerides. The possible determinants and potential beneficial effects of such a difference are briefly discussed.

Carbamylcholine and ouabain effects on Ca2+ handling and insulin release in islets from rats depleted in long-chain polyunsaturated omega 3 fatty acids.

A number of metabolic, ionic and secretory variables were recently found to be affected in pancreatic islets obtained from second generation rats depleted in long-chain polyunsaturated omega 3 fatty acids (omega 3 rats). The present study further documents three sets of anomalies in such islets. First, after 90 min exposure to D-glucose (8.3 mM), the release of insulin from perifused islets, prelabelled with 45Ca, is lower in omega 3 rats than in control animals, despite comparable 45Ca fractional outflow rate. Second, over 15 min exposure to carbamylcholine (0.1 mM), in the presence of D: -glucose, the cytosolic concentration of Ca2+ is increased to a greater relative extent in dispersed islet cells from omega 3 rats, as compared to control animals. This coincides with a greater relative increase in insulin output from perifused islets during the second phase of the secretory response to the cholinergic agent. Last, the increase provoked by ouabain (1.0 mM) in cytosolic Ca2+ concentration, 45Ca fractional outflow rate and insulin release are all delayed in the omega 3 rats. Taking into account the decreased activity of Na+, K+-ATPase in the islets of omega 3 rats, these findings are interpreted as reflecting an impaired priming of insulin-producing cells when first exposed for 105 min to a physiological postprandial concentration of D-glucose.

Intravenous fish oil blunts the physiological response to endotoxin in healthy subjects.

OBJECTIVE: To assess the effects of intravenous fish oil fat emulsion on the metabolic alterations induced by lipopolysaccharide (LPS) challenge in healthy volunteers. DESIGN: Two groups of eight healthy subjects were randomized to receive either two pharmacological doses of intravenous FO fat emulsion or no treatment. The FO group received twice 0.5 g/kg 10% emulsion (Omegaven) 48 and 24h before investigation. LPS (2 ng/kg) was injected as a bolus on the investigation day. Systemic parameters, indirect calorimetry, heart rate variability, and platelet membrane phospholipid composition were measured. RESULTS: Basal EPA and DHA content in platelet phospholipids was low (0.28% and 2.54%, respectively) and increased significantly after FO to 1.68% and 3.32%. LPS induced reproducible effects in all subjects. Fever was higher in the control [corrected] group than in FO group [corrected] the difference was significant from t (120) until t (360). FO blunted the neuroendocrine response: the rise in plasma norepinephrine was sevenfold lower at t (120) while the ACTH peak was fourfold lower. Tumor necrosis factor alpha was significantly lower between t (360) and t (180) in the FO group. CONCLUSIONS: Two doses of intravenous FO fat emulsion modified the phospholipid composition of platelets in healthy subjects. FO blunted fever and increased the neuroendocrine and the inflammatory responses to LPS.

Rapid changes in liver lipid composition and pancreatic islet K+ handling and secretory behaviour provoked by the intravenous administration of a medium-chain triglyceride: fish oil emulsion to long-chain polyunsaturated omega3 fatty acid-depleted rats.

Second generation rats depleted in long-chain polyunsaturated omega3 fatty acids are currently used as an animal model for the insufficient dietary supply of such fatty acids often prevailing in Western populations. The present study deals mainly with the effects of a novel medium-chain triglyceride: fish oil emulsion (MCT:FO), as compared to a control medium-chain triglyceride:olive oil emulsion (MCT: OO), administered as an intravenous bolus to the omega3-depleted rats 60-120 min before sacrifice upon selected biochemical and biophysical variables. The major findings consisted of a severe decrease of the omega3 fatty acid content of liver lipids in non-injected omega3-depleted rats and its partial correction after injection of the MCT:FO emulsion. The omega3-depleted rats also displayed liver steatosis, increased incorporation of long-chain polyunsaturated omega6 fatty acids in liver phospholipids and increased activity of liver Delta9-desaturase. As judged from the effects of ouabain upon 86Rb net uptake by isolated pancreatic islets, the activity of Na+,K+-ATPase was virtually abolished in the omega3-depleted rats. The latter defect was corrected by prior intravenous injection of the MCT:FO emulsion, this coinciding with suppression of the excessive secretory response to a number of insulin secretagogues otherwise observed in the islets of omega3-depleted rats injected or not with the MCT:OO emulsion.

Preclinical investigations of a medium-chain triglyceride:fish oil emulsion III. Experiments in cultured endothelial cells.

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion was recently reported to provoke a rapid and sustained increase in the cell phospholipid content of long-chain polyunsaturated omega3 fatty acids in both rats and human subjects. This report deals mainly with a comparison between this and other emulsions, as well as albumin-bound omega3 fatty acids, in terms of the time course, reversibility and concentration dependency for the incorporation of the omega3 fatty acids in the phospholipids of cultured endothelial cells. The results document that the new emulsion is quite efficient for a rapid and sustained enrichment of phospholipids in long-chain polyunsaturated omega3 fatty acids. The potential beneficial effects of such an enrichment in terms of aortic endothelial and cardiac function are emphasized.

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.

Protection of aortic endothelial function in both normal and diabetic rats by intravenous bolus injection of a medium-chain triglyceride: fish oil emulsion.

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion (MCT:FO) was recently proposed as a tool to provoke a rapid and sustained increase of cell phospholipid content in long-chain polyunsaturated omega3 fatty acids, for instance in selected subjects prior to anesthesia and surgery. In this study, therefore, the possible protective effect of MCT:FO upon aortic endothelial function was investigated in both normal and diabetic rats. The animals were injected intravenously 20 h before sacrifice with 1.0 ml of either saline, MCT:FO or a control medium-chain triglyceride:long-chain triglyceride emulsion. The vasomotor response of isolated aortic rings was then explored by assessing the relaxation provoked by increasing concentrations of acetylcholine in rings contracted with phenylephrine. Such measurements were performed before and after exposure of the aortic rings to suitable concentrations of oxidized LDL. In both normal and diabetic rats, the prior injection of the MCT:FO emulsion protected the aortic rings against the deleterious effect of oxidized LDL. In the diabetic rats, a beneficial effect of the MCT:FO emulsion was even observed prior to exposure of the aortic rings to oxidized LDL. These findings support the view that this novel procedure is indeed appropriate to protect endothelial function against oxidative stress.

Preclinical investigations of a medium-chain triglyceride:fish oil emulsion. I. Effects of bovine milk lipoprotein lipase on lipid composition.

The bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion (MCT:FO, 8:2, w:w) was recently found to increase within 60 min the leucocyte and platelet phospholipid content of long-chain polyunsaturated omega3 fatty acids. The present report deals with the effects of bovine milk lipoprotein lipase on the lipid composition of this emulsion. The results are compared to those obtained with either a pure fish oil emulsion or a medium-chain triglyceride: long-chain triglyceride:fish oil emulsion (MLF, 5:4:1). Emphasis is placed on i) differences in the fate of distinct fatty acids initially present in the triglycerides, di glycerides and phospholipids, ii) the generation of unesterified fatty acids relative to their initial content in each emulsion, and iii) the time course for these various events. The comparison between the three emulsions under consideration also provides information relevant to their respective sensitivity to lipoprotein lipase and suitability in terms of the generation of distinct unesterified fatty acids, including long-chain polyunsaturated omega3 fatty acids. Furthermore, attention is drawn to the greater efficiency for the hydrolysis of fatty acids from diglycerides as compared to triglycerides and a transient increase in the paired C8:0/C10:0 ratio in the diglycerides generated from the MCT:FO or MLF emulsion. The present study thus affords novel information relevant to the possible use of the MCT:FO emulsion in human subjects.

Sustained enrichment of liver phospholipids and triglycerides in eicosapentaenoate after a bolus intravenous injection of a medium-chain triglycerides:fish oil emulsion to streptozotocin (Type 1) and Goto-Kakizaki (Type 2) diabetic rats.

This study deals with the sustained enrichment of liver phospholipids and triglycerides in long-chain polyunsaturated omega3 fatty acids (omega3) found after the bolus intravenous injection of a novel medium-chain triglyceride:fish oil emulsion (MCT:FO) to streptozotocin (Type 1) and Goto-Kakizaki (Type 2) diabetic rats. Twenty hours after injection of the MCT:FO emulsion, the relative concentration of omega3 was indeed higher in liver phospholipids and triglycerides than that found in rats injected with either saline or a control medium-chain triglyceride:long-chain triglyceride emulsion. This coincided with a decrease in the ponderal percentage of C18:3omega3, C20:4omega6 and/or C22:4omega6 in liver triglycerides. The present study further documents differences between streptozotocin-induced and Goto-Kakizaki diabetic rats in terms of body weight, glycemia, liver triglyceride content and the fatty acid pattern of both liver phospholipids and triglycerides, as well as a close correlation in the latter animals between liver and plasma phospholipids or triglycerides as far as the ratio in the relative concentration of selected fatty acids representative of desaturase and elongase activities is concerned. In light of these and previous findings, it is proposed that the beneficial metabolic and functional events of the MCT:FO emulsion may display not solely a rapid but also sustained time course.

In vivo and in vitro properties of an intravenous lipid emulsion containing only medium chain and fish oil triglycerides.

BACKGROUND & AIMS: The triglyceride (TG) fatty acyl composition in lipid emulsions influences their metabolism. Little is known about the effects of long chain omega-3 polyunsaturated fatty acids (PUFA) on lipid emulsion metabolism. We investigated possible differences between omega-3 containing emulsions in their metabolism and tissue-targeting in vivo in a mouse model, and in vitro using lipolysis and cell culture experiments. METHODS: Soy oil (LCT), MCT/LCT/omega-3 (5:4:1, wt/wt/wt), and MCT/omega-3 (8:2, wt/wt) emulsions were radiolabeled with nondegradable 1alpha,2alpha (n)-[3H] cholesteryl oleoyl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection. Blood samples obtained over 25 min and extracted organs were used to measure the tissue distribution of lipid emulsion particles. Lipoprotein lipase (LpL)-mediated hydrolysis experiments and cell uptake studies in cultured J774 murine macrophages were also performed. RESULTS: Blood clearance of 8:2 was 13.4% and 29.8% faster compared to 5:4:1 and LCT, respectively. LCT had greatest liver uptake. LpL-mediated hydrolysis was greatest in 8:2 and lowest in LCT. Overall, cell TG accumulation in the presence of apolipoprotein E was least with 8:2. CONCLUSIONS: Our data shows that 8:2 had the most efficient blood clearance but less hepatic uptake in vivo. In vitro, 8:2 had both highest hydrolysis by LpL and intracellular TG utilization in the presence of apoE. Thus, an 8:2 lipid emulsion undergoes efficient blood clearance and may direct omega-3 PUFA more towards extrahepatic tissues.