Soybean Oil-based Lipid Emulsion Research Articles

Mixed Oil-Based Lipid Emulsions vs Soybean Oil-Based Lipid Emulsions on Incidence and Severity of Intestinal Failure-Associated Liver Disease in a Neonatal Intensive Care Unit.

Neonates requiring long-term parenteral nutrition (PN) are at risk for developing intestinal failure-associated liver disease (IFALD). The purpose of this study was to compare the incidence and severity of IFALD in a highly surgical neonatal population receiving mixed oil-based lipid emulsions (MOLEs) vs soybean oil-based lipid emulsions (SOLEs) for long-term PN. This retrospective cohort study evaluated patients admitted to a neonatal intensive care nursery that received PN for ≥14 days. Patients were separated into 2 cohorts; those who received SOLE and those who received MOLE. The primary outcome of this study was the occurrence of IFALD. Secondary outcomes included time to IFALD, peak bilirubin level during therapy, incidence of hypertriglyceridemia, bronchopulmonary dysplasia, and retinopathy of prematurity. A total of 107 patients were included in the study, IFALD occurred in 44.8% of patients receiving SOLE compared with 30% of patients receiving MOLE (relative risk, 0.67; 95% CI, 0.39-1.15). In the multivariable analysis, adjusting for the known confounders (prematurity, necrotizing enterocolitis, presence of ostomy, and duration of PN and lipids), the type of lipids was not a significant predictor for development of IFALD. Duration of PN and duration of lipids were determined to be significant risk factors for IFALD, regardless of type of lipid emulsion (odds ratio, 1.03; 95% CI, 1.01-1.05). Use of MOLE resulted in no significant difference in the outcomes studied when compared with SOLE. Duration of PN and duration of lipids were significant risk factors for development of IFALD.

Very low birth weight preterm infant complications where parenteral nutrition is soy or fish oil-based: A retrospective study in Shanghai.

To examine whether a parenteral mixed lipid emulsion containing fish oil reduces the incidence of cholestasis, retinopathy of prematurity (ROP) and bronchopulmonary dysplasia (BPD) in very low birth weight (VLBW, birth weight <1500 g) infants. This retrospective study was conducted in the neonatal intensive care unit of the Children's Hospital of Fudan University. Patients received either a soybean and medium-chain oil (MCT)-based lipid emulsion (Lipofundin) or a mixed lipid emulsion consisting of soybean oil, medium-chain triglycerides, olive oil, and fish oil (SMOF) as parenteral nutrition. The primary outcomes were cholestasis, ROP and BPD, and the secondary outcomes were necrotizing enterocolitis (NEC) and sepsis. A total of 149 premature infants (78 in the soybean oil group and 71 in the fish oil group) were included in this study. Multivariate logistic regression analysis showed that gestational age was associated with the incidence of ROP [odds ratio: 0.446, 95% confidence interval (CI): 0.332-0.576, p<0.001] and BPD [odds ratio: 0.428, 95% CI: 0.316-0.555, p<0.001]. The type of lipid emulsion had no statistically significant effect on any other neonatal morbidity. Both fish oil-containing and soybean oil-based parenteral lipid emulsions are safe and well-tolerated by preterm infants. However, the use of the SMOF lipid emulsion did not significantly reduce the incidence of cholestasis, ROP and BPD in VLBW infants.

Comparison of Soybean-based Oil and MCT-olive-fish-soy Oil Intravenous Lipid Emulsions on Soluble Adhesion Markers in Preterm Neonates with Sepsis: A Randomized Controlled Trial

To compare the effects of two different intravenous lipid emulsions on soluble adhesion markers in preterm infants with sepsis. This randomized controlled pilot trial was conducted from February 2016 to February 2017. 40 preterm infants with sepsis were enrolled and assigned to receive either Medium chain triglyceride-Olive-Fish-Soy lipid emulsion (MOFS-LE) or soybean oil-based lipid emulsion (S-LE). Outcomes of the study were changes in sICAM-1 and leukocyte integrin b2 levels, and growth after 7 days of intervention. Leukocyte integrin b2 was significantly higher in MOFS-LE group. No statistically significant differences were observed for sICAM-1, duration of mechanical ventilation and antibiotics treatment, and mortality rate. Leukocyte integrin b2 was significantly higher in preterm septic neonates who received MOFS-LE.

Lipid emulsions for parenterally fed term and late preterm infants.

Lipid emulsions for parenterally fed term and late preterm infants.

Lipid emulsions for parenterally fed preterm infants.

Lipid emulsions for parenterally fed preterm infants.

A Mixed Lipid Emulsion Containing Fish Oil and Its Effect on Electrophysiological Brain Maturation in Infants of Extremely Low Birth Weight: A Secondary Analysis of a Randomized Clinical Trial

To assess whether parenteral nutrition for infants of extremely low birth weight using a mixed lipid emulsion that contains fish oil influences electrophysiological brain maturation. The study is a prespecified secondary outcome analysis of a randomized controlled trial of 230 infants of extremely low birth weight receiving a mixed (soybean oil, medium-chain triglycerides, olive oil, and fish oil; intervention) or a soybean oil-based lipid emulsion (control). The study was conducted at a single-level IV neonatal care unit (Medical University Vienna; June 2012 to October 2015). Electrophysiological brain maturation (background activity, sleep-wake cycling, and brain maturational scores) was assessed biweekly by amplitude-integrated electroencephalography (birth to discharge). A total of 317 amplitude-integrated electroencephalography measurements (intervention: n=165; control: n=152) from 121 (intervention: n=63; control: n=58) of 230 infants of the core study were available for analysis. Demographic characteristics were not significantly different. By 28weeks of postmenstrual age, infants receiving the intervention displayed significantly greater percentages of continuous background activity. Total maturational scores and individual scores for continuity, cycling, and bandwidth were significantly greater. Maximum maturational scores were reached 2weeks earlier in the intervention group (36.4weeks, 35.4-37.5) compared with the control group (38.4weeks, 37.1-42.4) (median, IQR; P<.001). Using a mixed parenteral lipid emulsion that contains fish oil, we found that electrophysiological brain maturation was accelerated in infants who were preterm. ClinicalTrials.gov: NCT01585935.

Influence of n-3 Fish Oil-Enriched Intravenous Lipid Emulsion on Length of Stay and Mortality in Infants Post Intestinal Surgery

Background: Parenteral nutrition plays an important role in the infants post intestinal surgery. Currently, n-6 soybean oil-based intravenous lipid emulsion (IVLE) is used as a standard. n-6 have been shown increases biomarkers of inflammation while n-3 have shown positively influence clinical outcomes due to their immunomodulatory action. The aim of this study is to investigate the influence of n-3 fish oil-enriched IVLE on mortality and length of stay in infants post intestinal surgery. Methods: A medical record retrospective study was undertaken in infants post intestinal surgery at Dr. Soetomo Hospital in 2016-2017. Infants with intestinal atresia who had PN for at least three days were included. The n-6 soybean oil-based and n-3 fish oil-enriched IVLE were used. Incomplete data was excluded. Results: There were 19 infants (12/19 boys) included in this study. 10/19 infants received the n-6 soybean oil-based IVLE. The duration and dose of IVLE used were 16.52±11.34 days and 1.80±0.44 g/kg/day. Mortality rate was significantly lower in n-3 fish oil-enriched IVLE group (P=0.02) while there was no difference on length of stay (P=0.484).Conclusion: Infants who received the n-3 fish oil-enriched IVLE have a lower mortality rate but there is no difference on length of stay. Keywords: Infants, Intestinal surgery, Intravenous lipid emulsion, Length of stay, Mortality

Four-oil intravenous lipid emulsion effect on plasma fatty acid composition, inflammatory markers and clinical outcomes in acutely ill patients: A randomised control trial (Foil fact)

Data in critically ill patients on the effect of intravenous lipid emulsions (LEs), containing omega-3 polyunsaturated fatty acids (PUFAs), in parenteral nutrition (PN) are scarce and conflicting. This study compared the effects of a four-oil LE (30% soybean oil, 30% medium-chain triglycerides, 25% olive oil and 15% fish oil (FO)) (SMOFlipid®) to those of a 100% soybean oil-based LE in critically ill adult intensive care unit (ICU) patients. In this double-blind, randomised study, patients (n=75) predicted to need PN for more than 5 days were randomised to receive either a four-oil LE (Study Group (SG)) or a 100% soybean oil LE (Control Group (CG)). Isocaloric, isonitrogenous PN was administered continuously for 5 days. FO was provided at a dose of 0.09-0.22g/kg body weight. Measurements included biochemical parameters and sequential organ failure assessment (SOFA) score daily and plasma total phospholipid fatty acids (FAs) and cytokine levels on days 1, 3, 6. Days on mechanical ventilation, length of stay and mortality were also recorded. ANOVA was used to compare response variables between the two groups over the time and Pearson correlation was used to measure relationships between continuous variables. 68 patients completed the study (n=35 SG, n=33 CG), with male predominance (66% SG, 56% CG). Average age was 60.8±13.9 years (SG) versus 55.7±14.8 (CG) (p=0.143). The majority were surgical admissions (85% SG versus 91% CG) followed by medical. Plasma phospholipid oleic acid (p=0.022) and alpha-linolenic acid (p<0.0005) increased in both groups. In the SG, plasma phospholipid EPA and DHA increased (both p<0.001), whereas the omega-6:omega-3 PUFA (n-6:n-3 PUFA) ratio decreased (p<0.001). Aspartate aminotransferase (AST), alanine aminotransferase (ALT) and bilirubin decreased in both treatment groups. Considering only the change from day 1 to day 6 there was a bigger decrease in AST, ALT and bilirubin levels in the SG. Concentrations of TNF-α decreased from day 1 to day 6 in the SG, whereas they increased in the CG, but the change was not statistically significant (p=0.112). A significant negative correlation was found between EPA provision on day 3 and the SOFA score (r=-0.4047, p=0.018). Days on mechanical ventilation (1.24±0.83 days in SG versus 0.88±1.63 days in CG, p=0.385) and ICU LOS (9.5±7.09 days in SG versus 10.7±7.6 days in CG, p=0.490) were not different between groups. PN containing a four-oil LE increased plasma EPA and DHA, decreased n-6:n-3 PUFA ratio, and was safe and well tolerated. The negative relationship between day 3 EPA and SOFA score seems promising, but EPA intake and effects may have been diluted by enteral nutrition which was started in more than half of patients on day 4. There was no significant difference in terms of other biochemical measurements, SOFA score, length of ICU stay and mortality. More research is needed in this patient population, particularly regarding dose, duration and timing of FO and the effects on clinical outcomes.

Parenteral Nutrition Associated Liver Toxicity: Prevention, Diagnosis and Management

Long-term parenteral nutrition (PN) treatment is limited by parenteral nutrition–associated liver disease (PNALD), which is characterized initially by intrahepatic cholestasis, typically defined as a direct bilirubin greater than 2 mg/dL in the absence of other causes of liver disease. PNALD is typically less common and less severe and progresses more slowly in older children and adults than in infants. The etiology of PNALD is multifactorial. Key factors include immature liver function, sepsis, and a lack of enteral nutrition. Additionally, nearly every component of PN has been attributed to or exacerbated hepatotoxicity. PN preparations must be carefully individualized and monitored to minimize hepatotoxicity from its various components. Although many hepatotoxic components or imbalances have been recognized, soybean oil–based lipid emulsions continue to be widely used as they are the only lipid emulsions currently approved for PN by the Food and Drug Administration. Fish oil–based lipid emulsions have been shown to reverse PNALD, with an associated decrease in mortality. As such, fish oil therapy should be considered early once biochemical cholestasis is detected in PN-dependent patients. Studies investigating the use of novel lipid emulsions for prevention and treatment of PNALD are ongoing. This review contains 5 figures, 5 tables, and 114 references.

A Mixed Lipid Emulsion for Prevention of Parenteral Nutrition Associated Cholestasis in Extremely Low Birth Weight Infants: A Randomized Clinical Trial

ObjectivesTo examine whether a mixed lipid emulsion reduces the incidence of parenteral nutrition associated cholestasis (PNAC) in extremely low birth weight (ELBW, <1000 g) infants.Study designThis double-blind randomized trial of 230 ELBW infants (June 2012-October 2015) was performed at a single level IV neonatal intensive care unit. Patients received either a mixed lipid emulsion composed of soybean oil, medium chain triglycerides, olive oil, and fish oil-(intervention) or a soybean oil-based lipid emulsion (control) for parenteral nutrition. The primary outcome measure was PNAC (conjugated bilirubin >1.5 mg/dL [25 μmol/L] at 2 consecutive measurements). The study was powered to detect a reduction of PNAC from 25% to 10%.ResultsReasons for noneligibility of 274 infants screened were refusal to participate (n = 16), death (n = 10), withdrawal of treatment (n = 5), higher order multiples (n = 9), and parents not available for consent (n = 4). Intention to treat analysis was carried out in 223 infants (7 infants excluded after randomization). Parenteral nutrition associated cholestasis was 11 of 110 (10.1%) in the intervention and 18 of 113 (15.9%) in the control group (P = .20). Multivariable analyses showed no statistically significant difference in the intention to treat (aOR 0.428, 95% CI 0.155-1.187; P = .10) or per protocol population (aOR 0.457, 95% CI 0.155-1.347; P = .16). There was no statistically significant effect on any other neonatal morbidity.ConclusionsThe incidence of parenteral nutrition associated cholestasis was not significantly reduced using a mixed lipid emulsion in ELBW infants.Trial RegistrationClinicalTrials.gov NCT01585935.

Characterization of Fatty Acid Profiles in Infants With Intestinal Failure-Associated Liver Disease.

The purpose of this study was to characterize fatty acid profiles (FAPs) in parenteral nutrition (PN)-dependent infants with intestinal failure-associated liver disease (IFALD) receiving soybean oil-based lipid emulsion (SO) doses of ∼3 and ∼1 g/kg/d. Prospectively collected data were retrospectively reviewed. Serum FAPs of patients <1 year old who experienced development of IFALD while receiving standard PN with SO were examined before transitioning to a fish oil-based lipid emulsion for IFALD treatment. Time on SO, dose, gestational age, and weight- and length-for-age z scores were also reviewed. Among the 49 patients analyzed, there were no differences in demographics or anthropometrics between patients who received standard SO (SO-S) (n = 14, range of dosage 2.06-3.31 g/kg/d) and reduced SO (SO-R) (n = 35, range of dosage 0.90-1.34 g/kg/d). Patients received SO for a median of 53 days (interquartile range 39, 73) before FAP measurement. Patients who received SO-R had significantly higher Mead acid and lower α-linolenic, eicosapentaenoic, linoleic, stearic, total ω-3, and total ω-6 fatty acid levels than patients who received SO-S (P < .01). Triene:tetraene ratios were higher in patients who received SO-R (P = .0009), and no patients experienced biochemical essential fatty acid deficiency (EFAD). PN-dependent infants with IFALD receiving SO-R have different FAPs than patients receiving SO-S. No patients in either group had biochemical EFAD.

Parenteral Nutrition Associated Liver Toxicity: Prevention, Diagnosis and Management

Long-term parenteral nutrition (PN) treatment is limited by parenteral nutrition–associated liver disease (PNALD), which is characterized initially by intrahepatic cholestasis, typically defined as a direct bilirubin greater than 2 mg/dL in the absence of other causes of liver disease. PNALD is typically less common and less severe and progresses more slowly in older children and adults than in infants. The etiology of PNALD is multifactorial. Key factors include immature liver function, sepsis, and a lack of enteral nutrition. Additionally, nearly every component of PN has been attributed to or exacerbated hepatotoxicity. PN preparations must be carefully individualized and monitored to minimize hepatotoxicity from its various components. Although many hepatotoxic components or imbalances have been recognized, soybean oil–based lipid emulsions continue to be widely used as they are the only lipid emulsions currently approved for PN by the Food and Drug Administration. Fish oil–based lipid emulsions have been shown to reverse PNALD, with an associated decrease in mortality. As such, fish oil therapy should be considered early once biochemical cholestasis is detected in PN-dependent patients. Studies investigating the use of novel lipid emulsions for prevention and treatment of PNALD are ongoing. This review contains 5 figures, 5 tables, and 114 references.

Nutritional Risk Factors in the Pathogenesis of Parenteral Nutrition-Associated Liver Disease

Parenteral nutrition has been a lifesaving therapy for individuals who cannot sustain adequate oral or enteral nutrient intake to maintain fluid, electrolyte, and nutrient balance. Nonetheless, parenteral nutrition can lead to an increased risk of complications, such as parenteral nutrition-associated liver disease (PNALD). The pathogenesis of PNALD has been associated with multiple risk factors, such as longer duration, reduced small bowel length, decreased enteral intake, and bacterial infections. Nutritional risk factors also play an important role in the development of PNALD. This review presents several nutrient deficiencies and excesses that have been associated with PNALD. Deficiencies in certain nutrients (amino acids, essential fatty acids, enteral intake), excesses of certain nutrients (calories, carbohydrates, lipids), types of lipid emulsions, and mineral toxicities (aluminum, copper, manganese) have been associated with PNALD. Strategies to address PNALD require correction of these risk factors. The use of newer mixed lipid emulsions (including soybean, medium-chain triglycerides, olive oil, and fish oil) may also have less hepatotoxicity than traditional soybean oil-based lipid emulsions. Knowledge of nutritional risk factors for PNALD will help the clinician in the systematic evaluation and treatment of these specific risk factors. Moreover, an understanding of their effects guides the balance between addressing the patient’s nutritional needs and reducing the risk of PNALD.

Omega-3 fatty acids inhibit oxidative stress in a rat model of liver regeneration.

PurposeLipid peroxidation and consequent reactive oxygen species in the setting of oxidative stress have crucial roles in liver regeneration, which may adversely affect the regeneration itself and lead to liver failure. The aim of the current study is to investigate whether omega-3 fatty acid supplementation inhibits oxidative stress in an experimental model of liver regeneration.MethodsForty rats were allocated to four groups. Rats in group A received a sham operation. Rats in group B were subjected to right portal vein ligation (RPVL) and saline infusion. Rats in groups C and D were subjected to RPVL and total parenteral nutrition (TPN) with an all-in-one admixture containing a soybean oil based lipid emulsion. Rats in group D were additionally supplemented with omega-3 fatty acid infusion. Oxidative stresses in the blood and liver were measured by glutathione, superoxide dismutase, catalase, glutathione peroxidase, malondialdehyde, and nitric oxide.ResultsOmega-3 supplementation to the TPN solution significantly corrected alterations in the blood and tissue concentrations of oxidants and anti-oxidants during regeneration (P < 0.05).ConclusionOmega-3 fatty acid supplementation to the TPN solution revealed promising results in removal of oxidative stress that emerges during liver regeneration.

Sodium butyrate attenuates soybean oil-based lipid emulsion-induced increase in intestinal permeability of lipopolysaccharide by modulation of P-glycoprotein in Caco-2 cells

Down-regulation of intestinal P-glycoprotein (P-gp) by soybean oil-based lipid emulsion (SOLE) may cause elevated intestinal permeability of lipopolysaccharide (LPS) in patients with total parenteral nutrition, but the appropriate preventative treatment is currently limited. Recently, sodium butyrate (NaBut) has been demonstrated to regulate the expression of P-gp. Therefore, this study aimed to address whether treatment with NaBut could attenuate SOLE-induced increase in intestinal permeability of LPS by modulation of P-gp in vitro. Caco-2 cells were exposed to SOLE with or without NaBut. SOLE-induced down-regulation of P-gp was significantly attenuated by co-incubation with NaBut. Nuclear recruitment of FOXO 3a in response to NaBut was involved in P-gp regulation. Transport studies revealed that SOLE-induced increase in permeability of LPS was significantly attenuated by co-incubation with NaBut. Collectively, our results suggested that NaBut may be a potentially useful medication to prevent SOLE-induced increase in intestinal permeability of LPS.

Population Semiphysiologic Kinetic Modeling and Simulation of Plasma Triglyceride Levels After Soybean Oil-Based Intravenous Lipid Emulsion Administration in Rats.

Soybean oil-based intravenous lipid emulsion (SO-ILE) has clinical utility as an energy source and in lipid rescue therapy. However, an excessive infusion rate of SO-ILE in routine use and in lipid rescue therapy may cause serious side effects. There is little information about plasma triglyceride (TG) kinetics following SO-ILE administration. The present study aimed to develop a population semiphysiologic kinetic model of TG and to predict the TG kinetics even at extremely high concentrations in rats. TG concentration profiles after intravenous bolus (0.1, 0.25, 0.5, 1.0, 1.5, and 2.0 g/kg) or infusion (3.0 g/kg/h for 1 hour) of SO-ILE to rats were analyzed by a kinetic model constructed with 4 pathways: apolipoprotein acquisitions, zero-order catabolism, first-order uptake to storage sites, and zero-order secretion from storage sites. The developed model was subjected to internal and external validation. Plasma TG concentrations appeared to decline in a biphasic manner with nonlinear TG kinetics. The developed kinetic model was well validated and found to accurately predict the external validation data. The proposed kinetic model accurately described TG concentrations after SO-ILE administration at various infusion rates, including a lipid rescue regimen. The maximum acceptable infusion rate of SO-ILE in routine use should correspond to the maximum velocity of the apolipoprotein acquisition: 0.619 g/kg/h in rats. The prediction of TG kinetics at extremely high concentrations will provide useful information for lipid rescue therapy.

Skipped BSCL2 Transcript in Celia's Encephalopathy (PELD): New Insights on Fatty Acids Involvement, Senescence and Adipogenesis.

ObjectivePELD (Progressive Encephalopathy with or without Lipodystrophy or Celia’s Encephalopathy) is a fatal and rare neurodegenerative syndrome associated with the BSCL2 mutation c.985C>T, that results in an aberrant transcript without the exon 7 (Celia seipin). The aim of this study was to evaluate both the process of cellular senescence and the effect of unsaturated fatty acids on preadipocytes from a homozygous c.985C>T patient. Also, the role of aberrant seipin isoform on adipogenesis was studied in adipose-derived human mesenchymal stem cells.Material and methodsCellular senescence was evaluated using β-galactosidase staining of preadipocytes obtained from a homozygous c.985C>T patient. Moreover, these cells were cultured during 24 hours with Intralipid, a soybean oil-based commercial lipid emulsion. The expression of the different BSCL2 transcripts was measured by qPCR. Adipose-derived human mesenchymal stem cells were differentiated to a fat lineage using StemPRO adipogenesis kit, and the expression of BSCL2 transcripts and several adipogenesis-related genes was measured by qPCR.Resultsthe treatment of preadipocytes with unsaturated fatty acids significantly reduced the expression of the BSCL2 transcript without exon 7 by 34 to 63%. On the other hand, at least in preadipocytes, this mutation does not disturb cellular senescence rate. Finally, during adipocyte differentiation of adipose-derived human mesenchymal stem cells, the expression of adipogenic genes (PPARG, LPIN1, and LPL) increased significantly over 14 days, and noteworthy is that the BSCL2 transcript without exon 7 was differentially expressed by 332 to 723% when compared to day 0, suggesting an underlying role in adipogenesis.Conclusionsour results suggest that Celia seipin is probably playing an underestimated role in adipocyte maturation, but not in senescence, and its expression can be modified by exogenous factors as fatty acids.

The Effect of Fish Oil-Based Lipid Emulsion and Soybean Oil-Based Lipid Emulsion on Cholestasis Associated with Long-Term Parenteral Nutrition in Premature Infants.

Purpose. To retrospectively study the effect of fish oil-based lipid emulsion and soybean oil-based lipid emulsion on cholestasis associated with long-term parenteral nutrition in premature infants. Methods. Soybean oil-based lipid emulsion and fish oil-based lipid emulsion had been applied in our neonatology department clinically between 2010 and 2014. There were 61 qualified premature infants included in this study and divided into two groups. Soybean oil group was made up of 32 premature infants, while fish oil group was made up of 29 premature infants. Analysis was made on the gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, age at which feeding began, usage of lipid emulsions, and incidence of cholestasis between the two groups. Results. There were no statistical differences in terms of gender, feeding intolerance, infection history, birth weight, gestational age, duration of parenteral nutrition, total dosage of amino acid, and age at which feeding began. Besides, total incidence of cholestasis was 21.3%, and the days of life of occurrence of cholestasis were 53 ± 5.0 days. Incidence of cholestasis had no statistical difference in the two groups. Conclusion. This study did not find the different role of fish oil-based lipid emulsions and soybean oil-based lipid emulsions in cholestasis associated with long-term parenteral nutrition in premature infants.

Differential Impacts of Soybean and Fish Oils on Hepatocyte Lipid Droplet Accumulation and Endoplasmic Reticulum Stress in Primary Rabbit Hepatocytes.

Parenteral nutrition-associated liver disease (PNALD) is a severe ailment associated with long-term parenteral nutrition. Soybean oil-based lipid emulsions (SOLE) are thought to promote PNALD development, whereas fish oil-based lipid emulsions (FOLE) are thought to protect against PNALD. This study aimed to investigate the effects of SOLE and FOLE on primary rabbit hepatocytes. The results reveal that SOLE caused significant endoplasmic reticulum (ER) and mitochondrial damage, ultimately resulting in lipid droplets accumulation and ER stress. While these deleterious events induce hepatocyte injury, FOLE at high doses cause only minor ER and mitochondrial damage, which has no effect on hepatic function. SOLE also significantly upregulated glucose-regulated protein 94 mRNA and protein expression. These data indicate that SOLE, but not FOLE, damage the ER and mitochondria, resulting in lipid droplets accumulation and ER stress and, finally, hepatocyte injury. This likely contributes to the differential impacts of SOLE and FOLE on PNALD development and progression.

Soybean Oil-Based Lipid Emulsion Increases Intestinal Permeability of Lipopolysaccharide in Caco-2 Cells by Downregulation of P-Glycoprotein via ERK-FOXO 3a Pathway

Background and Aims: Elevated intestinal permeability of lipopolysaccharide (LPS) is a major complication for patients with parenteral nutrition (PN), but the pathogenesis is poorly understood. Intestinal P-glycoprotein (P-gp) is one of the efflux transporters that contribute to restricting the permeability of lipopolysaccharide via transcellular route. P-gp expression may be regulated by PN ingredients, and thus this study sought to investigate the effect of PN on the expression of P-gp and to elucidate the underlying mechanism in vitro. Methods: Caco-2 cells were treated with PN ingredients. Changes in P-gp expression and function were determined and the role of ERK-FOXO 3a pathway was studied. Transport studies of FITC-lipopolysaccharide (FITC-LPS) across Caco-2 cell monolayers were also performed. Results: Among PN ingredients, soybean oil-based lipid emulsion (SOLE) exhibited significant inhibitory effect on P-gp expression and function. This regulation was mediated via activation of ERK pathway with subsequent nuclear exclusion of FOXO 3a. Importantly, P-gp participated in antagonizing the permeation of FITC-LPS (apical to basolateral) across Caco-2 cell monolayers. SOLE significantly increased the permeability of FITC-LPS (apical to basolateral), which was associated with impaired P-gp function. Conclusions: The expression and function of intestinal P-gp is suppressed by SOLE in vitro.