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

Department of Department of Pediatrics, Columbia University, New York

Yvon A. Carpentier, MD

Department of Surgery, Universite Libre de Bruxelles, Relgium

Rajasekhar Ramakrishnan, ScD

Department of Department of Pediatrics, Columbia University, New York, Institute of Human Nutrition, Columbia University, New York

Maysoon Al-Haideri, PhD

Department of Department of Pediatrics, Columbia University, New York

Toru Seo, PhD

Department of Department of Pediatrics, Columbia University, New York

Richard J. Deckelbaum, MD

Department of Department of Pediatrics, Columbia University, New York, Institute of Human Nutrition, Columbia University, New York

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 -3 TG emulsions showed similar delivery to liver (39% ± 3.9%, 46% ± 3.6%, 34% ± 3.2%). Liver uptake of LCT/MCT/-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 -3 TG emulsion from the blood compared with emulsion in which -3 TG was mixed with LCT and MCT. Earlier data showed that -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 -3 TG with LCT/MCT will result in greater delivery of -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)

Journal of Parenteral and Enteral Nutrition, Vol. 23, No. 5, 253-259 (1999)
DOI: 10.1177/0148607199023005253


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