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Title: METHY1-B-CYCLODEXTRIN CAN BE USED AS A CARRIER FOR INTRAVENOUS INFUSION OF PALMITATE DURING TRACER STUDIES

Author
item Wray Cahen, Diane
item Caperna, Thomas
item Steele, Norman

Submitted to: Annals of Nutrition and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 8/23/1999
Publication Date: N/A
Citation: N/A

Interpretive Summary: Typically fatty acid-free albumin is used as a carrier for intravenous infusion of fatty acids to study in vivo lipid metabolism. However, subjects can experience negative reactions to albumin infusion. We sought a non-blood-derived alternative to albumin for infusion of labeled fatty acids in pigs. Cyclodextrins are naturally-occurring water-soluble molecules that can serve as carriers for lipid-soluble compounds, such as fatty acids. 13C-palmitate was complexed to either 20% methyl-B- cyclodextrin, 20% 2-hydroxypropyl-B-cyclodextrin, or 5% porcine albumin. Palmitate remained in solution at 4#C in methyl-B-cyclodextrin, but precipitated at 25-30#C in 2-hydroxypropyl-B-cyclodextrin. After a 13C-bic ate infusion, palmitate-albumin complex was infused under fed conditions and palmitate-methyl-B-cyclodextrin was infused under fasted and fed conditions in 50 kg pigs to determine the metabolism and oxidation of infused 13C- palmitate. Pigs infused with palmitate-methyl-B-cyclodext xture maintained normal body temperature and appetite; those infused with palmitate / albumin became anorexic and exhibited other negative side effects to albumin. Breath 13CO2 and plasma 13C- palmitate enrichments under fed conditions were similar for methyl-B-cyclodextrin and albumin. Fasting increased palmitate-methyl-B-cyclodextrin oxidation greater than 6-fold. These data suggest that methyl- -cyclodextrin may be a suitable substitute for albumin in fatty acid metabolism studies.

Technical Abstract: Typically fatty acid-free albumin (ALB) is used as a carrier for intravenous (IV) infusion of fatty acids (FA) to study in vivo lipid metabolism. However, subjects can have adverse reactions to infusion of ALB. We sought an alternative to ALB for IV infusion of FA, using the pig as a model. Cyclodextrins (CDEX) are naturally-occurring water-soluble molecules that can serve as carriers for lipid-soluble compounds. Methods: 13C-palmitate (PA) was complexed to either 20% methyl-B-CDEX (MBC), 20% 2-hydroxypropyl-B-CDEX (HPBC), or 5% porcine ALB (0.3g PA/10g CDEX or ALB). PA-ALB was infused under fed conditions and PA-MBC was infused under fasted and fed conditions in 50 kg pigs to determine the metabolism and oxidation of infused PA. Results: PA remained in solution at 4#C in MBC, but precipitated at 25-30#C in HPBC (PA-HPBC was therefore not suitable for IV infusion). Pigs infused with PA-MBC maintained normal body temperature and appetite; those infused with PA-ALB became anorexic and exhibited other negative side effects to ALB. PA oxidation rates under fed conditions were similar using either PA-MBC or PA-ALB complexes. Fasting increased PA/MBC oxidation >6-fold. Conclusion: These data suggest that MBC may be a suitable substitute for ALB in FA metabolism studies.