Résumé : Background & aims: The triglyceride (TG) fatty acyl composition in lipid emulsions influences their metabolism. Little is known about the effects of long chain ω-3 polyunsaturated fatty acids (PUFA) on lipid emulsion metabolism. We investigated possible differences between ω-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/ω-3 (5:4:1, wt/wt/wt), and MCT/ ω-3 (8:2, wt/wt) emulsions were radiolabeled with nondegradable 1α,2α (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 ω-3 PUFA more towards extrahepatic tissues. © 2005 Elsevier Ltd. All rights reserved.