Intravenous lipid emulsions designed to meet preterm infant requirements increase plasma and tissue levels of docosahexaenoic acid and arachidonic acid in mice.

Autor: Fligor SC; Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Tsikis ST; Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Hirsch TI; Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Quigley M; Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA., Pan A; Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA., Kishikawa H; Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA., Mitchell PD; Biostatistics and Research Design Center, Boston Children's Hospital, Boston, MA, USA., Gura KM; Harvard Medical School, Boston, MA, USA; Department of Pharmacy and the Division of Gastroenterology, Hepatology, and Nutrition, Boston Children's Hospital, Boston, MA, USA., Puder M; Vascular Biology Program and the Department of Surgery, Boston Children's Hospital, Boston, MA, USA; Harvard Medical School, Boston, MA, USA. Electronic address: Mark.Puder@childrens.harvard.edu.
Jazyk: angličtina
Zdroj: Clinical nutrition (Edinburgh, Scotland) [Clin Nutr] 2024 Oct; Vol. 43 (10), pp. 2273-2285. Date of Electronic Publication: 2024 Aug 23.
DOI: 10.1016/j.clnu.2024.08.019
Abstrakt: Background & Aims: Intravenous lipid emulsions used in preterm infants contain insufficient docosahexaenoic acid (DHA) and arachidonic acid (ARA) to support normal development, resulting in deficiencies that contribute to complications of prematurity and cognitive delay. We sought to investigate the effects of new intravenous lipid emulsions designed to contain sufficient DHA and ARA to meet preterm needs, while avoiding liver toxicity.
Methods: Three new lipid emulsions (NLE A-C) were laboratory-generated using high pressure homogenization. First, a long-term experiment evaluated the impact on plasma, liver, and frontal cortex fatty acid composition compared to commercially available lipid emulsions. Lipid emulsions were administered via daily orogastric gavage to four-week-old C57Bl/6 J mice. Next, liver toxicity was evaluated in a murine model of parenteral nutrition-induced hepatosteatosis. Mice were provided an ad lib fat-free high carbohydrate diet, with intravenous lipid emulsion administration every other day for 19 days.
Results: Administration of commercially available lipid emulsions (soybean oil, mixed oil, or fish oil) resulted in decreased plasma and tissue levels of DHA and/or ARA compared to a chow control. The new lipid emulsions demonstrated a dose-response effect in plasma and tissue concentration of DHA and ARA. NLE C (with an approximately even DHA:ARA ratio), compared to chow, maintained similar DHA (19.2 ± 0.3 vs. 19.3 ± 0.3%, P = 1.00) and ARA (10.4 ± 0.2 vs. 9.9 ± 0.2% ARA, P = 0.75) content in frontal cortex tissue. All three new lipid emulsions prevented biochemical liver injury and pathologist-assessed hepatosteatosis; soybean oil lipid emulsion and mixed oil lipid emulsion treatment resulted in hepatosteatosis in both experiments.
Conclusion: Long-term treatment with the new lipid emulsions in juvenile mice resulted in increased plasma and tissue DHA and/or ARA content compared to currently available lipid emulsions. The new lipid emulsions also prevented hepatosteatosis and biochemical liver injury with enteral and parenteral administration.
Competing Interests: Conflict of Interest statement A patent application has been filed by SF, KG, and MP entitled “Methods and Compositions Relating to Treatment and Prevention of Fatty Acid Deficiencies.” KG and MP also hold a patent related to the use of fish oil lipid emulsion for the treatment of parenteral nutrition-associated cholestasis.
(Copyright © 2024 Elsevier Ltd and European Society for Clinical Nutrition and Metabolism. All rights reserved.)
Databáze: MEDLINE
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