A Comparison of Fish Oil Sources for Parenteral Lipid Emulsions in a Murine Model

ABSTRACT Background Fish oil (FO) intravenous lipid emulsions (ILEs) are used as a monotherapy to treat parenteral nutrition (PN)-associated liver disease and provide essential fatty acids (EFAs) needed to sustain growth and prevent EFA deficiency (EFAD). Studies have suggested that medium-chain triglycerides (MCTs) and α-tocopherol have anti-inflammatory properties. Objective The purpose of this study was to test whether FO-ILEs containing MCTs and/or additional α-tocopherol decrease the inflammatory response to an endotoxin challenge compared with FO-ILE alone and preserve the ability to prevent PN-induced liver injury in mice. Methods A murine model of PN-induced hepatosteatosis was used to compare the effects of ILEs formulated in the laboratory containing varying ratios of FO and MCTs, and subsequently FO- and 50:50 FO:MCT-ILE plus 500 mg/L α-tocopherol (FO + AT and 50:50 + AT, respectively). C57BL/6 mice receiving unpurified diet (UPD), PN-equivalent diet (PN) + saline, and PN + soybean oil (SO)-ILE served as controls. After 19 d, mice received an intraperitoneal saline or endotoxin challenge 4 h before being killed. Serum and livers were harvested for histologic analysis, fatty acid profiling, and measurement of systemic inflammatory markers (tumor necrosis factor-α, interleukin-6). Results All ILEs were well tolerated and prevented biochemical EFAD. Livers of mice that received saline and SO developed steatosis. Mice that received 30:70 FO:MCT developed mild hepatosteatosis. All other FO-containing ILEs preserved normal hepatic architecture. Mice that received FO- or SO-ILE had significantly elevated systemic inflammatory markers after endotoxin challenge compared with UPD-fed controls, whereas 50:50 FO:MCT, 30:70 FO:MCT, FO + AT, and 50:50 + AT groups had significantly lower inflammatory markers similar to those seen in UPD-fed controls. Conclusions Mixed FO/MCT and the addition of α-tocopherol to FO improved the inflammatory response to endotoxin challenge compared with FO-ILE alone while still preventing PN-induced liver injury and EFAD in mice. There was no synergistic relation between α-tocopherol and MCTs.

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Faculty Opinions recommendation of Parenteral fish oil lipid emulsions in the critically ill: a systematic review and meta-analysis.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.718006589.793501246 ◽

2014 ◽

Author(s):

Todd Rice

Keyword(s):

Systematic Review ◽

Fish Oil ◽

Critically Ill ◽

Meta Analysis ◽

Lipid Emulsions

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

Nutrients ◽

10.3390/nu13010205 ◽

2021 ◽

Vol 13 (1) ◽

pp. 205

Author(s):

William Yakah ◽

David Ramiro-Cortijo ◽

Pratibha Singh ◽

Joanne Brown ◽

Barbara Stoll ◽

...

Keyword(s):

Fatty Acid ◽

Fish Oil ◽

Soybean Oil ◽

Inflammatory Responses ◽

Postnatal Period ◽

Lipid Emulsions ◽

Omega 3 ◽

Oil Emulsion ◽

Mixed Oil ◽

The Impact

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.

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Influence of Fish Oil-Containing Lipid Emulsions on Parenteral Nutrition-Associated Liver Disease in Neonates

Journal of Clinical Nutrition ◽

10.15747/jcn.2017.9.1.21 ◽

2017 ◽

Vol 9 (1) ◽

pp. 21-29

Author(s):

Jeong-A Park ◽

Ji-Eun Park ◽

Min-Jae Jeong ◽

Jae-Song Kim ◽

Eun-Sun Son ◽

...

Keyword(s):

Liver Disease ◽

Parenteral Nutrition ◽

Fish Oil ◽

Lipid Emulsions

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Phytosterolaemia associated with parenteral nutrition administration in adult patients

British Journal Of Nutrition ◽

10.1017/s0007114520000574 ◽

2020 ◽

Vol 123 (12) ◽

pp. 1365-1372 ◽

Cited By ~ 1

Author(s):

Josep M. Llop-Talaveron ◽

Elisabet Leiva-Badosa ◽

Ana Novak ◽

Raúl Rigo-Bonnin ◽

Josep R. Ticó-Grau ◽

...

Keyword(s):

Parenteral Nutrition ◽

Fish Oil ◽

Total Cholesterol ◽

Great Variability ◽

Adult Patients ◽

Lipid Emulsions ◽

Patient Study ◽

Hospitalised Patients

AbstractVegetable lipid emulsions (LE) contain non-declared phytosterols (PS). We aimed to determine PS content depending on the brand and LE batch, and in adult hospitalised patients treated with parenteral nutrition (PN), to establish the association between plasma and administered PS. Part I was the LE study: totals and fractions of PS in three to four non-consecutive batches from six LE were analysed. Part II was the patient study: patients with at least 7 previous days of PN with 0·8 g/kg per d of an olive/soyabean (O/S) LE were randomised (day 0) 1:1 to O/S or 100 % fish oil (FO) at a dose of 0·4 g/kg per d for 7 d (day 7). Plasma PS, its fractions, total cholesterol on days 0 and 7, their clearance and their association with PS administered by LE were studied. In part I, LE study: differences were found in the total PS, their fractions and cholesterol among different LE brands and batches. Exclusive soyabean LE had the highest content of PS (422·36 (sd 130·46) μg/ml). In part II, patient study: nineteen patients were included. In the O/S group, PS levels were maintained (1·11 (sd 6·98) μg/ml) from day 0 to 7, while in the FO group, significant decreases were seen in total PS (−6·21 (sd 4·73) μg/ml) and their fractions, except for campesterol and stigmasterol. Plasma PS on day 7 were significantly associated with PS administered (R2 0·443). PS content in different LE brands had great variability. PS administered during PN resulted in accumulation and could be prevented with the exclusive administration of FO LE.

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Intravenous Lipid Emulsions to Deliver Bioactive Omega-3 Fatty Acids for Improved Patient Outcomes

Marine Drugs ◽

10.3390/md17050274 ◽

2019 ◽

Vol 17 (5) ◽

pp. 274 ◽

Cited By ~ 11

Author(s):

Philip C. Calder

Keyword(s):

Fatty Acids ◽

Parenteral Nutrition ◽

Fish Oil ◽

Hospital Stay ◽

Critically Ill ◽

Adult Patients ◽

Lipid Emulsions ◽

Omega 3 Fatty Acids ◽

Omega 3 ◽

Meta Analyses

Lipids used in intravenous nutrition support (i.e., parenteral nutrition) provide energy, building blocks, and essential fatty acids. These lipids are included as emulsions since they need to be soluble in an aqueous environment. Fish oil is a source of bioactive omega-3 fatty acids (eicosapentaenoic acid and docosahexaenoic acid). Lipid emulsions, including fish oil, have been used for parenteral nutrition for adult patients post-surgery (mainly gastrointestinal). This has been associated with alterations in biomarkers of inflammation and immune defense, and in some studies, a reduction in length of intensive care unit and hospital stay. These benefits, along with a reduction in infections, are emphasized through recent meta-analyses. Perioperative administration of fish oil may be superior to postoperative administration, but this requires further exploration. Parenteral fish oil has been used in critically ill adult patients. Here, the influence on inflammatory processes, immune function, and clinical endpoints is less clear. However, some studies found reduced inflammation, improved gas exchange, and shorter length of hospital stay in critically ill patients if they received fish oil. Meta-analyses do not present a consistent picture but are limited by the small number and size of studies. More and better trials are needed in patient groups in which parenteral nutrition is used and where fish oil, as a source of bioactive omega-3 fatty acids, may offer benefits.

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Intravenous fish oil lipid emulsion promotes a shift toward anti-inflammatory proresolving lipid mediators

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00106.2013 ◽

2013 ◽

Vol 305 (11) ◽

pp. G818-G828 ◽

Cited By ~ 30

Author(s):

Brian T. Kalish ◽

Hau D. Le ◽

Jonathan M. Fitzgerald ◽

Samantha Wang ◽

Kyle Seamon ◽

...

Keyword(s):

Liver Disease ◽

Fish Oil ◽

Lipid Emulsion ◽

Lipid Mediators ◽

Lipid Emulsions ◽

Serum Samples ◽

Human Infants ◽

Life Threatening ◽

Small Cohort ◽

Anti Inflammatory

Parenteral nutrition (PN)-associated liver disease (PNALD) is a life-threatening complication of the administration of PN. The development of PNALD may be partly due to the composition of the lipid emulsion administered with PN: soybean oil-based lipid emulsions (SOLE) are associated with liver disease, while fish oil-based lipid emulsions (FOLE) are associated with prevention and improvement of liver disease. The objective of this study was to determine how the choice of lipid emulsion modified the production of bioactive lipid mediators (LMs). We utilized a mouse model of steatosis to study the differential effect of FOLE and SOLE. We subsequently validated these results in serum samples from a small cohort of human infants transitioning from SOLE to FOLE. In mice, FOLE was associated with production of anti-inflammatory, proresolving LMs; SOLE was associated with increased production of inflammatory LMs. In human infants, the transition from SOLE to FOLE was associated with a shift toward a proresolving lipidome. Together, these results demonstrate that the composition of the lipid emulsion directly modifies inflammatory homeostasis.

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