Blood clearance and tissue uptake of intravenous lipid emulsions containing long-chain and medium-chain triglycerides and fish oil in a mouse model.
BACKGROUND
Increasing interest in using different triglycerides (TGs) for specific clinical applications raised the question as to how the emulsion TG composition would affect blood clearance and emulsion delivery to hepatic and extrahepatic tissues.


METHODS
Emulsions used were long-chain soy oil TG (long-chain triglyceride [LCT]), LCT/ medium-chain triglyceride (MCT; 1:1, wt/wt), LCT/MCT/C/omega-3 (5:4:1, wt/wt) and pure fish oil (omega-3 TG) labeled with non-degradable 3H-cholesteryl oleoyl ether (3H-CE) as a particle marker. Mice (C57BL/6J) were injected with four different commercial emulsions at a nonsaturating dose of 0.4 mg TG/20 to 25 g per mouse to obtain 1st order kinetics. Blood was sampled at 0.5, 2, 5, 10, 15, and 25 minutes, and the fractional catabolic rate was determined by fitting a straight line to the logarithm of the blood 3H-CE radioactivity. Retention of 3H-CE for each tissue at 25 minutes reflected organ uptake of the emulsion.


RESULTS
Blood clearance of pure omega-3 TG (10.40% +/- 0.54% pools/h; mean +/- SE) was significantly slower than that of LCT, LCT/MCT, and LCT/MCT/omega-3 emulsion (18.9 +/- 0.6 pools/h, 17.0 +/- 0.96 pools/h, 16.5 +/- 1.08 pools/h, respectively) (p < .01). Based on 3H-CE uptake, LCT, LCT/MCT, and omega-3 TG emulsions showed similar delivery to liver (39% +/- 3.9%, 46% +/- 3.6%, 34% +/- 3.2%). Liver uptake of LCT/MCT/omega-3, (23% +/- 2.2%) was less than LCT/MCT (46% +/-3.6%, p < .0001) and LCT (39% +/- 3.9%, p = .002).


CONCLUSIONS
Results indicate slow blood clearance of pure omega-3 TG emulsion from the blood compared with emulsion in which omega-3 TG was mixed with LCT and MCT. Earlier data showed that omega-3 TG are poorly hydrolyzed in extracellular media and therefore are delivered to tissues as part of the core of emulsion remnants. Thus, our data suggest that the incorporation of omega-3 TG with LCT/MCT will result in greater delivery of omega-3 fatty acids to extrahepatic tissue, which could be important in modulating immune and other responses.
Treskova
E
E
Department of Pediatrics, Columbia University, New York 10032, USA.
Carpentier
Y A
YA
Ramakrishnan
R
R
Al-Haideri
M
M
Seo
T
T
Deckelbaum
R J
RJ
D000818:Animals; D005217:Fat Emulsions, Intravenous / Q000378:metabolism / Q000493:pharmacokinetics*; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage / Q000097:blood / Q000493:pharmacokinetics; D005395:Fish Oils / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D007700:Kinetics; D008099:Liver / Q000378:metabolism; D008657:Metabolic Clearance Rate; D051379:Mice; D008810:Mice, Inbred C57BL; D014280:Triglycerides / Q000008:administration & dosage* / Q000097:blood / Q000493:pharmacokinetics; D014316:Tritium
D005217:Fat Emulsions, Intravenous; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D014280:Triglycerides; D014316:Tritium