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

Background Et Aims: The triglyceride (TG) fatty acyl composition in tipid emulsions influences their metabolism. Little is known about the effects of long chain omega-3 polyunsaturated fatty acids (PUFA) on tipid 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 radiotabeled with nondegradable 1 alpha,2 alpha (n)-[H-3] chotesteryl oleoyl ether to trace core particle metabolism in C57BL/6J mice following a bolus injection. Blood samples obtained over 25min 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. (c) 2005 Elsevier Ltd. All rights reserved.