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Cholesterol improves the utilization of parenteral lipid emulsions

Cholesterin verbessert die Verwertung von Fettemulsionen für die künstliche Ernährung

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Zusammenfassung

Fettemulsionen sind eine unverzichtbare Komponente der parenteralen Ernährung geworden. Derzeit verfügbare Emulsionen haben eine weitgehend identische Zusammensetzung aus Pflanzenölen und Eigelb-Phospholipiden als Emulgator. Frühere Versuche, die Zusammensetzung zu optimieren, haben sich weitgehend auf die Triglyzeridzusammensetzung fokussiert. Als erste grundsätzliche Änderung ihrer Zusammensetzung seit ihrer Einführung in die klinische Medizin haben wir eine Emulsion untersucht, die als Zusatz freies Cholesterin enthält.

Bei 10 gesunden männlichen normolipämischen Freiwilligen haben wir die Elimination, Hydrolyse und die Fettoxydation (gemessen mittels indirekter Kalorimetrie) unter Infusion einer herkömmlichen Fettemulsion (20% Triglyzeride) gegenüber einer sonst identischen Emulsion, der ex ovo 4 g/l freies Cholesterin zugesetzt wurde, verglichen.

Unter Infusion der Cholesterin-hältigen Fettemulsion war der Anstieg der Plasmatriglyzeride vermindert (323,8±27,5 vs. 202,0±18,9 mg·dL−1, p<0,001), die Eliminationshalbwertszeit der Triglyzeride verkürzt (41,6±5,4 vs. 29,3±5,1 min, p<0,05), und die Gesamtkörper-clearance erhöht (0,96±0,1 vs. 1,52±0,2 ml·b.w.·min−1, p<0,02). Auch war der Anstieg der Freien Fettsäuren (400,7±39,0 vs. 532,2±64,0 μmol·L−1; p<0,02) und der Ketonkörper (β-hydroxy Butyrat) (151,6±37,0 vs. 226,3±33,01 μmol·L−1; p<0,02) im Plasma erhöht, der Anstieg von Insulin und Glukagon vermindert (p<0,05). Ebenso war unter Infusion der modifizierten Emulsion der Abfall des respiratorischen Quotienten ausgeprägter und der Anteil der Fett-Oxydation am Gesamtkörperenergie-umsatz gesteigert (66,2%±6,0 vs. 70,9%±6,3, p<0,05). Eine Beeinträchtigung des Gasaustausches oder andere Nebenwirkungen konnten nicht nachgewiesen werden.

Zusammenfassend zeigen diese Ergebnisse, dass die Elimination einer Cholesterin-supplementierten Fettemulsion für die parenterale Ernährung beschleunigt, die Triglyzerid-Hydrolyse gesteigert und die Fettoxydation erhöht ist. Dies bedeutet, dass der Zusatz von Cholesterin zu einer Fettemulsion nicht nur eine Möglichkeit bietet, das möglicherwiese bei akutkranken Patienten krankheitsbedingt essentiell werdende Cholesterin zuzuführen, sondern auch, dass dies hilft, künstlichen Fettpartikeln eine Chylomikron-ähnlichere Struktur zu geben und dadurch die Fett-Verwertung zu verbessern.

Summary

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 triglycerdes 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 μmol·L−1; p<0.02) and ketone bodies (β-hydroxybutyrate) (151.6±37.0 vs. 226.3±33.01 μmol·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 chylomicronresembling composition and improve lipid utilization.

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  1. Abteilung für Nephrologie, Klinik für Innere Medizin III, Währinger Gürtel 18-20, A-1090, Vienna, Austria

    Wilfred Druml MD & Margot Fischer

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  1. Wilfred Druml MD
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Correspondence to Wilfred Druml MD.

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Druml, W., Fischer, M. Cholesterol improves the utilization of parenteral lipid emulsions. Wien Klin Wochenschr 115, 767–774 (2003). https://doi.org/10.1007/BF03040501

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