Parenteral Fish-Oil Containing Lipid Emulsions Limit Initial Lipopolysaccharide-Induced Host Immune Responses in Preterm Pigs.

William Yakah,Barbara Stoll,Raina N Fichorova,Joanne Brown,Doug Burrin,Madhulika Kulkarni,Camilia R Martin,Krishna Rao Maddipati,Berthe C Oosterloo,Pratibha Singh,David Ramiro-Cortijo,Steven D Freedman

doi:10.3390/nu13010205

Abstract

Multicomponent lipid emulsions are available for critical care of preterm infants. We sought to determine the impact of different lipid emulsions on early priming of the host and its response to an acute stimulus. Pigs delivered 7d preterm (n = 59) were randomized to receive different lipid emulsions for 11 days: 100% soybean oil (SO), mixed oil emulsion (SO, medium chain olive oil and fish oil) including 15% fish oil (MO15), or 100% fish oil (FO100). On day 11, pigs received an 8-h continuous intravenous infusion of either lipopolysaccharide (LPS—lyophilized Escherichia coli) or saline. Plasma was collected for fatty acid, oxylipin, metabolomic, and cytokine analyses. At day 11, plasma omega-3 fatty acid levels in the FO100 groups showed the highest increase in eicosapentaenoic acid, EPA (0.1 ± 0.0 to 9.7 ± 1.9, p < 0.001), docosahexaenoic acid, DHA (day 0 = 2.5 ± 0.7 to 13.6 ± 2.9, p < 0.001), EPA and DHA-derived oxylipins, and sphingomyelin metabolites. In the SO group, levels of cytokine IL1β increased at the first hour of LPS infusion (296.6 ± 308 pg/mL) but was undetectable in MO15, FO100, or in the animals receiving saline instead of LPS. Pigs in the SO group showed a significant increase in arachidonic acid (AA)-derived prostaglandins and thromboxanes in the first hour (p < 0.05). No significant changes in oxylipins were observed with either fish-oil containing group during LPS infusion. Host priming with soybean oil in the early postnatal period preserves a higher AA:DHA ratio and the ability to acutely respond to an external stimulus. In contrast, fish-oil containing lipid emulsions increase DHA, exacerbate a deficit in AA, and limit the initial LPS-induced inflammatory responses in preterm pigs.

Highlights

The third trimester of pregnancy is an essential phase of the growing human fetus, marked by an exponential increase in brain and lung maturation as well as an accumulation of adequate immunonutrients in adipose tissues [1,2]
We examined the effect of nutritional priming with different lipid emulsions on lipopolysaccharide (LPS)-induced acute inflammatory responses using a preterm pig model [18,19]
No significant difference in vital signs were recorded within the MO15 and FO100 lipid groups

Summary

Introduction

The third trimester of pregnancy is an essential phase of the growing human fetus, marked by an exponential increase in brain and lung maturation as well as an accumulation of adequate immunonutrients in adipose tissues [1,2]. Preterm birth results in early, postnatal deficits in long-chain polyunsaturated fatty acids (LCPUFAs), docosahexaenoic acid (DHA) and arachidonic acid (AA) [4]. Lipid emulsions such as Intralipid® , a commonly used soybean-oil emulsion, contains essential fatty acid precursors such as linoleic acid (LA) but little to no AA and/or DHA [5]. Despite its benefits in providing a parenteral fat source, the use of Intralipid® has been associated with increased pro-inflammatory markers [6] and parenteral nutrition associated cholestasis (PNAC) [7,8], when compared to the use of fish oil-containing emulsions containing omega-3 (n-3) LCPUFAs. Fish oil-containing emulsions such as Omegaven®

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