Blood Clearance and Tissue Uptake of Intravenous Lipid Emulsions Containing Long-Chain and Medium-Chain Triglycerides and Fish Oil in a Mouse Model

Abstract

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/w-3 (5:4:1, wt/wt) and pure fish oil (w-3 TG) labeled with nondegradable 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 w-3 TG (10.40% ± 0.54% pools/h; mean ± SE) was significantly slower than that of LCT, LCT/MCT, and LCT/MCT/w-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 ω-3 TG emulsions showed similar delivery to liver (39% ± 3.9%, 46% ± 3.6%, 34% ± 3.2%). Liver uptake of LCT/MCT/ω-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 ω-3 TG emulsion from the blood compared with emulsion in which ω-3 TG was mixed with LCT and MCT. Earlier data showed that ω-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 ω-3 TG with LCT/MCT will result in greater delivery of ω-3 fatty acids to extrahepatic tissue, which could be important in modulating immune and other responses. (Journal of Parenteral and Enteral Nutrition 23:253-259, 1999)

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References

Spielmann D. , Bracco U. , Traitler H. , et al: Alternative lipids to usual w6 PUFAS γ-linolenic acid, α-linolenic acid. stearidonic acid. EPA. etc. JPEN 12:1158-123S. 1988

Darlington LD Ramsey NW : Review of dietary therapy for rheumatoid arthritis. Comp Ther 20:490-494. 1994

Uauy R. Treen K. , Hoffman DR : Essential fatty acid metabolism and requirements during development . Semin Perinatol 13:118-130. 1989

Carpentier YA Simoens C. Siderova V. et al: Parenteral administration of n-3 fatty acids: Indications. experience and perspectives. IN n-3 Fatty Acids: Prevention and Treatment in Vascular Disease. Kristense SD. Schmidt EB eds Bi and Gi Publishers. London. 1995. pp 207-216

Horrobin DF : Fatty acid metabolism in health and disease: The role of delta-6-desaturase . Am J Clin Nutr 57:732S-736S. 1993

Salem N. Jr , Wegher B. Mena P. et al: Arachidonic and docosahexaenoic acids are bio-synthesized from their 18 carbon precursors in human infants. Proc Natl Acad Sci USA 93:49-54, 1996

Belluzi A. Brignola C. Campieri M. et al: Effect of an enteric coated fish oil preparation on relapse in Crohn's disease. N Engl J Med 334:15567-15560, 1996

Gersten H. : The use of n-3 PUFAs (fish oil) in enteral nutrition. Int J Vit Nutr Res 65:3-20, 1995

Razzini E. , Baronzio GF : Omega-3 fatty acids as coadjuvant treatment in AIDS. Med Hypotheses 41:300-305, 1993

10.

Carpentier YA : Intravascular metabolism of fat emulsions: The Arvid Wretlind Lecture, ESPEN 1988. Clin Nutr 8:115-125, 1988

11.

Deckelbaum RJ , Hamilton T. , Moser A. , et al: Medium chain vs long chain triacylglycerol emulsion hydrolysis by lipoprotein lipase and hepatic lipase implications for the mechanisms of lipase action. Biochemistry 29:1136-1142, 1990

12.

Olivecrona G. and Olivecrona T. : Clearance of artificial triacylglycerol particles . Curr Opin Clin Nutr Metab Care 1:143-151, 1998

13.

Hultin M. , Carneheim C. , Rosenqvist K. , et al: Intravenous lipid emulsions: Removal mechanisms as compared to chylomicrons. J Lipid Res 36:2174-2184, 1995

14.

Rensen P. , van Berkel T. : Apolipoprotein E effectively inhibits lipoprotein lipase-mediated lipolysis of chylomicron-like triglyceride-rich lipid emulsions in vitro and in vivo . J Biol Chem 271:14791-14799, 1996

15.

Bartlett GR : Phosphorus assay in column chromatography . J Biol Chem 234:466-468, 1959

16.

Van Bennekum AM , Kako Y. , Weinstock PH , et al: Lipoprotein lipase expression level influences tissue clearance of chylomicron retinyl ester. J Lipid Res 40:565-574, 1999

17.

Oliveira FLC , Rumsey SC , Schlotzer E. , et al: Triglyceride hydrolysis of soy oil vs fish oil emulsions. JPEN 21:224-228, 1997

18.

Melin T. , Qi C. , Bengtsson-Olivecrona G. , et al: Hydrolysis of chylomicron polyenoic fatty acid esters with lipoprotein lipase and hepatic lipase. Biochim Biophys Acta 1075:259-266, 1991

19.

Morley N. , Kuksis A. : Positional specificity of lipoprotein lipase. J Biol Chem 247:6389-6396, 1972

20.

Schwiegelshohn B. , Deckelbaum RJ , Hansen I. , et al: In vitro cell metabolism of plasma triglyceride is efficient after fish oil supplementation to LCT infusion in man. Clin Nutr (Abstr.) 12:34, 1993

21.

Hamberger L. , Carpentier YA , Hansen I. , et al: In vitro lipolysis of MCT and fish oil-containing emulsions: Evidence that longer chain fatty acids must be cleared as intact triglyceride in emulsion remnants. Clin Nutr (Abstr.) 15:23, 1996

22.

Hamilton JA , Vural J. , Carpentier YA , et al: Incorporation of medium chain triacylglycerols into phospholipid bilayers: The effect of long-chain triacylglycerols, cholesterol and cholesteryl esters. J Lipid Res 37:773-782, 1996

23.

Sato N. , Deckelbaum RJ , Neeser G. , et al: Hydrolysis of mixed lipid emulsions containing medium-chain and long-chain triacylglycerol with lipoprotein lipase in plasma-like medium . JPEN 18:112-118, 1994

24.

Hamberger L. Carpentier YA Keysennan F. , et al: More efficient clearance of intravenous lipid emulsions containing medium chain triglyceride and fish oil triglycerides as compared to traditionallong chain triglyceride lipid emulsions in in vitro models and humans (Abstr). FASEB J 12:A514. 1998

25.

Goldberg. IJ : Lipoprotein lipase lipolysis: Central role in lipoprotein metabolism and atherogenesis. J Lipid Res 34:693-707, 1996

26.

Carpentier YA Dubois DY Deckelbaum RJ : Plasma lipoproteins and intravenous lipid emulsions. IN Nutrition and Metabolism in the Surgical Patient . Fischer JE ed. Little . Brown & Company, New York , 1996, pp 237-265