title: Cholesterol improves the utilization of parenteral lipid emulsions.
abstract: Lipid emulsions have become an indispensable component of parenteral nutrition. Commercially available emulsions mostly have an identical composition of triglycerides (from plant oils) and egg-yolk phospholipids as emulsifier. Previous attempts to improve the composition of lipid emulsions have focused mainly on the triglyceride moiety. In the first fundamental modification of a lipid emulsion since their broader introduction into clinical medicine, we included free cholesterol in a lipid emulsion. We evaluated elimination and hydrolysis of triglycerides and lipid oxidation (by indirect calorimetry) in 10 healthy male normolipemic volunteers, comparing a conventional lipid emulsion (20% triglycerides) with an otherwise identical emulsion with the addition of 4 g/l free cholesterol. The rise in plasma triglycerides was mitigated during infusion of the cholesterol-enriched solution (323.8 +/- 27.5 vs. 202.0 +/- 18.9 mg.dL-1, p < 0.001), plasma half-life was reduced (41.6 +/- 5.4 vs. 29.3 +/- 5.1 min, p < 0.05), and total-body clearance was enhanced (0.96 +/- 0.1 vs. 1.52 +/- 0.2 ml.b.w.(.)min-1, p < 0.02). The rise in plasma free fatty acids (400.7 +/- 39.0 vs. 532.2 +/- 64.0 mumol.L-1; p < 0.02) and ketone bodies (beta-hydroxybutyrate) (151.6 +/- 37.0 vs. 226.3 +/- 33.01 mumol.L-1; p < 0.02) was augmented. Increases in plasma insulin and glucagon were less pronounced (p < 0.05). The fall in respiratory quotient was greater and the fraction of lipid oxidation as a percentage of total energy expenditure was increased (66.2% +/- 6.0 vs. 70.9% +/- 6.3, p < 0.05) during infusion of the modified solution. No impairment of gas exchange or other side effects were observed. Taken together these results indicate that the elimination of a cholesterol-supplemented lipid emulsion is accelerated, triglyceride hydrolysis is enhanced, and lipid oxidation is augmented. Thus, addition of cholesterol to a lipid emulsion might not only present a means of providing cholesterol in parenteral nutrition but also help to reshape artificial lipid particles to a more chylomicron-resembling composition and improve lipid utilization.
authors.affiliation: Division of Nephrology, IIIrd Medical Department, University of Vienna, Vienna, Austria. wilfred.druml@akh-wien.ac.at
authors.forename: Wilfred
authors.initials: W
authors.lastname: Druml
authors.forename: Margot
authors.initials: M
authors.lastname: Fischer
mesh_terms: D000328:Adult; D002151:Calorimetry; D002784:Cholesterol / Q000008:administration & dosage; D018592:Cross-Over Studies; D005217:Fat Emulsions, Intravenous / Q000493:pharmacokinetics; D005230:Fatty Acids, Nonesterified / Q000097:blood; D006801:Humans; D007657:Ketone Bodies / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D010084:Oxidation-Reduction; D010288:Parenteral Nutrition
chemical_list: D005217:Fat Emulsions, Intravenous; D005230:Fatty Acids, Nonesterified; D007657:Ketone Bodies; D002784:Cholesterol