Stimulation of gluconeogenesis by intravenous lipids in preterm infants: response depends on fatty acid profile

2006 ◽  
Vol 290 (4) ◽  
pp. E723-E730 ◽  
Author(s):  
Anne A. M. W. van Kempen ◽  
Saskia N. van der Crabben ◽  
Mariëtte T. Ackermans ◽  
Erik Endert ◽  
Joke H. Kok ◽  
...  

In preterm infants, both hypo- and hyperglycemia are a frequent problem. Intravenous lipids can affect glucose metabolism by stimulation of gluconeogenesis by providing glycerol, which is a gluconeogenic precursor, and/or free fatty acids (FFA), which are stimulants of the rate of gluconeogenesis. In 25 preterm infants, glucose production and gluconeogenesis were measured using stable isotope techniques during a 6-h infusion of glucose only, glucose plus glycerol, or glucose plus an intravenous lipid emulsion. Two lipid emulsions differing in FFA composition were used: Intralipid (∼60% polyunsaturated FFA) and Clinoleic (∼60% monounsaturated FFA). The rate of glucose infusion was 22 μmol·kg−1·min−1 in all groups. During the study infusion, the FFA concentrations were higher in both lipid groups vs. the glycerol group ( P < 0.001). Compared with baseline, the glucose production rate increased in the Intralipid group, whereas it decreased in the other groups ( P = 0.002) due to a significant increase in gluconeogenesis in the Intralipid group ( P = 0.016). The plasma glucose concentration was significantly higher during Intralipid infusion vs. the other groups ( P = 0.046). Our conclusion was that Intralipid enhanced glucose production by increasing gluconeogenesis in preterm infants. This can be ascribed to the stimulatory effect of FFA in addition to any effect of glycerol alone. The lack of stimulation of gluconeogenesis in the Clinoleic vs. the Intralipid group suggests that different classes of fatty acids exert different effects on glucose kinetics in preterm infants.

2020 ◽  
Vol 9 (7) ◽  
pp. 2048
Author(s):  
Matthias Hecker ◽  
Matthias Rose ◽  
Andreas Hecker ◽  
Hartmut Dietrich ◽  
Martina B. Schaefer ◽  
...  

Background: Acute respiratory distress syndrome (ARDS) is associated with both high morbidity and mortality in intensive care units worldwide. Patients with ARDS often require parenteral nutrition with lipid emulsions as essential components. In the present study, we assessed the immunomodulatory and apoptotic effects of a modern, n-6-reduced lipid emulsion mixture in murine ARDS. Methods: Mice received an infusion of either normal saline solution, pure long-chain triglyceride (LCT) emulsion, or SMOF (soybean oil, medium-chain triglycerides, olive oil, and fish oil) before a lipopolysaccharide (LPS) challenge. Mice were sacrificed at different time points (0, 24, or 72 h) after ARDS induction, and an analysis of inflammatory cytokines, protein concentrations, and the cellular composition of the alveolar and interstitial compartments was performed with special focus on alveolar apoptosis and necrosis. Results: Mice infused with SMOF showed decreased leukocyte invasion, protein leakage, myeloperoxidase activity, and cytokine production in alveolar spaces after LPS challenge compared to animals that received LCT. There were fewer cells in the lung interstitium of the SMOF group compared to the LCT group. Both lipid emulsions exerted pro-apoptotic and pro-necrotic properties on alveolar immune cells, with significantly increased necrosis in mice infused with LCT compared to SMOF. Conclusion: SMOF has both anti-inflammatory and pro-resolving influences in murine ARDS. Partial replacement of n-6 fatty acids with n-3/n-9 fatty acids may therefore benefit critically ill patients at risk for ARDS who require parenteral nutrition.


2019 ◽  
Author(s):  
Ana Suárez-Lledó ◽  
Elisabet Leiva Badosa ◽  
Josep M Llop Talaveron ◽  
Monica Fernandez Alvarez ◽  
Leandre Farran Teixidor ◽  
...  

Abstract Background Esophagectomy is a major surgical procedure with a high degree of catabolic and postsurgical inflammatory response that conditions a high morbidity and a significant mortality. Enteral administration of ω-3 fatty acids has been seen to be effective although its use is limited due to tolerance. There are few clinical trials with ω-3 fatty acids parenterally in these patients, so we propose to investigate the effect of combining a lipid emulsion rich in fish oil with the standard enteral nutrition support. Methods Prospective, single-center, randomized, double-blind study in patients diagnosed with esophageal cancer and after esophagectomy treated with a lipid emulsion rich in ω-3 fatty acid emulsion or a mixture of ω-6 long chain triglycerides (LCT) / short chain triglycerides (MCT) 50%. After surgery, these emulsions will be added to the standard nutritional support in continuous infusion until complete 5 days of treatment. Patients will be randomized 1:1:1 in Group A 0,4g/kg/day of lipid emulsion rich in fish oil; Group B 0,8g/kg/day of lipid emulsion rich in fish oil and Group C 0,8g/kg/day of LCT/MCT emulsion. The main objective is to determine whether the administration for 5 days of intravenous lipid emulsions rich in ω-3 fatty acids in patients after esophagectomy is effective in normalizing the interleukin-6 (IL6) compared with LCT/MCT emulsions, and if 0,8 g/kg/day dose is more effective than 0,4g/kg/day. Secondary outcomes include other inflammatory markers as C reactive protein (CRP), tumor necrosis factor alpha (TNF-a) and interleukin-10 (IL-10), and parameters of morbidity, safety, nutrition and mortality. Samples will be collected at the moment of surgery indication and on days 0, 1, 3, 5 and 21 to determine inflammatory, nutritional, hepatic and security parameters. In addition, clinical follow-up throughout the hospital stay and up to one year after surgery. Discussion There are few studies of fatty acids ω-3 administered via parenteral in oesophagectomized patients. This study proposes to investigate the effect of combining fish-oil lipid emulsions administered via parenteral with enteral nutrition support, implying benefits such as: fast incorporation of lipids to the cellular membranes and to the inflammatory cascade, and the use of only one pharmaconutrient.


2019 ◽  
Author(s):  
YI-LING WANG ◽  
Lih-Ju Chen ◽  
Lon-Yen Tsao ◽  
Hsiao-Neng Chen ◽  
Cheng-Han Lee ◽  
...  

Abstract Background Preterm infants received long-term parenteral nutrition (PN) due to gastrointestinal immaturity. Mixed lipid emulsions composed of soybean oil, medium chain triglycerides (MCTs), olive oil, and fish oil, which have a relatively low ω-6: ω-3 ratio, may decrease the incidence of PN-associated cholestasis by reducing oxidative stress and providing an anti-inflammatory effect.Methods The retrospective cohort study enrolled a total 399 very low birth weight (VLBW) premature infants between January 2009 and November 2017 at a single neonatal intensive care unit. Preterm infants received total parenteral nutrition with either mixed lipid emulsion (SMOFlipid, n = 195) or soybean oil-based lipid emulsion (Lipovenoes, n = 204) for at least seven days. We compared the outcomes of PN-associated cholestasis, co-morbidities and mortality.Results The incidence of PN-associated cholestasis was significantly lower in the SMOFlipid group than the Lipovenoes group (10.3% vs 20.1%, P = 0.006). The related clinical laboratory findings, including levels of γ- GT (P = 0.019), triglyceride (P < 0.001), and cholesterol (P = 0.023), were significantly lower in the SMOFlipid group. The duration to full feeding days shortened in the SMOFlipid group compared with the Lipovenoes group (25 ± 10.33 vs 33 ± 16.22, P < 0.001). Relevant complications, such as severe retinopathy of prematurity (ROP, 3.6% vs 14.3%, P < 0.001) and bronchopulmonary dysplasia (BPD, 36.9% vs 46.7%, P = 0.046) were also reduced in the SMOFlipid group versus the Lipovenoes group, but there was no significant effect on severe intraventricular hemorrhage (IVH), necrotizing enterocolitis (NEC), or mortality in both groups.Conclusions In very premature infants, PN with fish oil-based lipid emulsions is associated with a lower incidence of PN-associated cholestasis compared with soybean oil-based lipid emulsions.


2021 ◽  
Vol 49 (5) ◽  
pp. 030006052110118
Author(s):  
Yi-Ling Wang ◽  
Lih-Ju Chen ◽  
Lon-Yen Tsao ◽  
Hsiao-Neng Chen ◽  
Cheng-Han Lee ◽  
...  

Objective Preterm infants receive long-term parenteral nutrition (PN) for gastrointestinal immaturity. This study aimed to determine if mixed lipid emulsions containing fish oil decrease the incidence of PN-associated cholestasis by reducing oxidative stress and providing an anti-inflammatory effect. Methods This retrospective cohort study enrolled 399 very low birth weight premature infants (gestational age ≤32 weeks) between January 2009 and November 2017 at a single neonatal intensive care unit. Preterm infants received total PN with either mixed lipid emulsion including fish oil (SMOFlipid®, n = 195) or soybean oil-based lipid emulsion (Lipovenoes®, n = 204) for at least 7 days. We compared the outcomes of PN-associated cholestasis, comorbidities, and mortality between the groups. Results The incidence of PN-associated cholestasis was significantly lower in the SMOFlipid group than in the Lipovenoes group. The duration to full feeding days was significantly shorter in the SMOFlipid group compared with the Lipovenoes group. Relevant complications, such as severe retinopathy of prematurity and bronchopulmonary dysplasia, were also significantly reduced in the SMOFlipid group compared with the Lipovenoes group. Conclusion In premature infants, PN with fish oil-based lipid emulsions is associated with a lower incidence of PN-associated cholestasis compared with soybean oil-based lipid emulsions.


1961 ◽  
Vol 200 (3) ◽  
pp. 508-510 ◽  
Author(s):  
Robert B. Flinn ◽  
Bernard Leboeuf ◽  
George F. Cahill

The metabolism of C14-labeled glucose, fructose, mannose and pyruvate was studied in kidney slices from normal and alloxan-diabetic rats. Labeled carbon was recovered in CO2, glycogen and fatty acids. The rate of mannose metabolism was consistently slightly less than that of glucose, and on the other hand, the rate of fructose metabolism was consistently greater. In slices from alloxan-diabetic animals the metabolism of glucose and mannose was markedly reduced; that of fructose was only slightly decreased. No effect of insulin added in vitro could be demonstrated on glucose metabolism. Pyruvate oxidation to CO2 was slightly increased in slices from diabetic animals. Furthermore, glucose production was increased sixfold by diabetes and, as calculated, 75% of this glucose production could be accounted for by glucose synthesized from labeled pyruvate. The similarity between carbohydrate metabolism in liver and kidney was pointed out.


2011 ◽  
Vol 159 (1) ◽  
pp. 33-38.e1 ◽  
Author(s):  
Rita D’Ascenzo ◽  
Sabrina D’Egidio ◽  
Lorena Angelini ◽  
Maria Paola Bellagamba ◽  
Marco Manna ◽  
...  

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Tomohiro Komatsu ◽  
Toshihiro Sakurai ◽  
Anna Wolska ◽  
Marcelo J. Amar ◽  
Akiko Sakurai ◽  
...  

Aim. Plasma apolipoprotein C-II (apoC-II) activates lipoprotein lipase (LPL) and thus lowers plasma triglycerides (TG). We previously reported that a human apoC-II mimetic peptide (C-II-a) decreased plasma TG in apoC-II mutant mice, as well as in apoE-knockout mice. Because it is unknown what tissues take up free fatty acids (FFAs) released from TG after C-II-a peptide administration, we investigated in mice TG plasma clearance and tissue incorporation, using 3H-triolein as a tracer, with and without C-II-a treatment. Methods and Results. Intralipid® fat emulsion was labeled with 3H-triolein and then mixed with or without C-II-a. Addition of the peptide did not alter mean particle size of the lipid emulsion particles (298 nm) but accelerated their plasma clearance. After intravenous injection into C57BL/6N mice, the plasma half-life of the 3H-triolein for control and C-II-a treated emulsions was 18.3 ± 2.2 min and 14.8 ± 0.1 min, respectively. In apoC-II mutant mice, the plasma half-life of 3H-triolein for injected control and C-II-a treated emulsions was 30.1 ± 0.1 min and 14.8 ± 0.1 min, respectively. C57BL/6N and apoC-II mutant mice at 120 minutes after the injection showed increased tissue incorporation of radioactivity in white adipose tissue when C-II-a treated emulsion was used. Higher radiolabeled uptake of lipids from C-II-a treated emulsion was also observed in the skeletal muscle of C57BL/6N mice only. In case of apoC-II mutant mice, decreased uptake of radioactive lipids was observed in the liver and kidney after addition of C-II-a to the lipid emulsion. Conclusions. C-II-a peptide promotes the plasma clearance of TG-rich lipid emulsions in wild type and apoC-II mutant mice and promotes the incorporation of fatty acids from TG in the lipid emulsions into specific peripheral tissues.


2001 ◽  
Vol 281 (2) ◽  
pp. E375-E383 ◽  
Author(s):  
K. Fosgerau ◽  
S. D. Mittelman ◽  
A. Sunehag ◽  
M. K. Dea ◽  
K. Lundgren ◽  
...  

It has been proposed that the glycogenolytic and gluconeogenic pathways contributing to endogenous glucose production are interrelated. Thus a change in one source of glucose 6-phosphate might be compensated for by an inverse change in the other pathway. We therefore investigated the effects of 1,4-dideoxy-1,4-imino-d-arabinitol (DAB), a potent glycogen phosphorylase inhibitor, on glucose production in fasted conscious dogs. When dogs were treated acutely with high glucagon, glucose production rose from 1.93 ± 0.14 to 3.07 ± 0.37 mg · kg−1· min−1( P < 0.01). When dogs were treated acutely with DAB in addition to high glucagon infusion, the stimulation of the glycogenolytic rate was completely suppressed. Glucose production rose from 1.85 ± 0.20 to 2.41 ± 0.17 mg · kg−1· min−1( P < 0.05), which was due to the increase in gluconeogenesis from 0.93 ± 0.09 to 1.54 ± 0.08 mg · kg−1· min−1( P < 0.001). In conclusion, infusion of DAB inhibited glycogenolysis; however, the absolute contribution of gluconeogenesis to glucose production was not affected. These results suggest that inhibition of glycogenolysis could be an effective antidiabetic treatment.


2005 ◽  
Vol 94 (2) ◽  
pp. 221-230 ◽  
Author(s):  
A. García-de-Lorenzo ◽  
R. Denia ◽  
P. Atlan ◽  
S. Martinez-Ratero ◽  
A. Le Brun ◽  
...  

It has been claimed that lipid emulsions with a restricted linoleic acid content can improve the safety of total parenteral nutrition (TPN). The tolerability of TPN and its effects on the metabolism of fatty acids were assessed in this prospective, double-blind, randomised study comparing an olive/soyabean oil long-chain triacylglycerol (LCT) with a medium-chain triacylglycerol (MCT)/LCT; 50:50 (w) based lipid emulsion in two groups (O and M, respectively; eleven per group) of severely burned patients. After resuscitation (48–72 h), patients received TPN providing 147 kJ/kg per d (35 kcal/kg per d) with fat (1·3 g/kg per d) for 6 d Plasma fatty acids, laboratory parameters including liver function tests, and plasma cytokines were assessed before and after TPN. Adverse events encountered during TPN and the clinical outcomes of patients within the subsequent 6 months were recorded. With both lipid emulsions, the conversion of linoleic acid in its higher derivatives (di-homo-γ-linolenic acid) improved and essential fatty acid deficiency did not appear. Abnormalities of liver function tests occurred more frequently in the M (nine) than in the O (three) group (P=0·04, Suissa–Shuster test). Seven patients (four from group O and three from group M) died as a consequence of severe sepsis 3–37 d after completion of the 6 d TPN period. When compared with the surviving patients, those who died were older (P=0·01) and hyperglycaemic at baseline (P<0·001), and their plasma IL-6 levels continued to increase (P<0·04). Although fatty acid metabolism and TPN tolerability were similar with both lipid emulsions, the preservation of liver function noted with the use of the olive oil-based lipid emulsions deserves confirmation.


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