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 o-3 polyunsaturated fatty acids (PUFA) on lipid emulsion metabolism. We investigated possible differences between o-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/o-3 (5:4:1, wt/wt/wt), and MCT/o-3 (8:2, wt/ wt) emulsions were radiolabeled with nondegradable 1a,2a (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.