In vivo and in vitro properties of an intravenous lipid emulsion containing only medium chain and fish oil triglycerides.
OBJECTIVE
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.
Ton
Mimi N
MN
Division of Gastroenterology, Hepatology, & Nutrition, Department of Pediatrics, Columbia University Medical Center, New York, NY, USA.
Chang
Chuchun
C
Carpentier
Yvon A
YA
Deckelbaum
Richard J
RJ
D000818:Animals; D001057:Apolipoproteins E / Q000378:metabolism / Q000494:pharmacology; D005217:Fat Emulsions, Intravenous / Q000008:administration & dosage / Q000378:metabolism / Q000493:pharmacokinetics*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000378:metabolism / Q000494:pharmacology*; D005260:Female; D005395:Fish Oils / Q000008:administration & dosage*; D066298:In Vitro Techniques; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D011897:Random Allocation; D014018:Tissue Distribution; D014280:Triglycerides / Q000737:chemistry / Q000378:metabolism*
D001057:Apolipoproteins E; D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D014280:Triglycerides