Apolipoprotein C-II Mimetic Peptide Promotes the Plasma Clearance of Triglyceride-Rich Lipid Emulsion and the Incorporation of Fatty Acids into Peripheral Tissues of Mice

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.

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Immunomodulation by an Omega-6 Fatty Acid Reduced Mixed Lipid Emulsion in Murine Acute Respiratory Distress Syndrome

Journal of Clinical Medicine ◽

10.3390/jcm9072048 ◽

2020 ◽

Vol 9 (7) ◽

pp. 2048

Author(s):

Matthias Hecker ◽

Matthias Rose ◽

Andreas Hecker ◽

Hartmut Dietrich ◽

Martina B. Schaefer ◽

...

Keyword(s):

Fatty Acids ◽

Acute Respiratory Distress Syndrome ◽

Parenteral Nutrition ◽

Respiratory Distress Syndrome ◽

Respiratory Distress ◽

Lipid Emulsion ◽

Distress Syndrome ◽

Partial Replacement ◽

Lipid Emulsions ◽

Lps Challenge

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.

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Intravenous Lipid Emulsion Therapy for Bromethalin Toxicity in a Dog

Journal of the American Animal Hospital Association ◽

10.5326/jaaha-ms-6396 ◽

2016 ◽

Vol 52 (4) ◽

pp. 265-268 ◽

Cited By ~ 11

Author(s):

Brittany Heggem-Perry ◽

Maureen McMichael ◽

Mauria O'Brien ◽

Clara Moran

Keyword(s):

Central Nervous System ◽

Nervous System ◽

Veterinary Medicine ◽

Serum Sample ◽

Half Life ◽

Lipid Emulsion ◽

Second Generation ◽

Toxic Metabolite ◽

Lipid Emulsions ◽

Phase Out

ABSTRACT Bromethalin is a central nervous system toxin currently incorporated into several different rodenticides. In 2008, the EPA requested that manufacturers phase out second-generation anticoagulant rodenticides. In response, manufacturers began to increase production of bromethalin-based rodenticides. It is likely that pet exposure to bromethalin will increase in the future. Bromethalin has no known antidote and tends to deposit in fat. Intravenous lipid emulsions (ILEs) are being used with increasing frequency in both human and veterinary medicine to treat numerous acute systemic toxicities. A 4 yr old spayed female Pit bull terrier was presented following witnessed ingestion of bromethalin rodenticide by the owners. Decontamination was unsuccessful and ILE was started. Serum was frozen at −80°C before and 1 hr after completion of ILE. In rats, the half-life of desmethylbromethalin, the toxic metabolite, has been reported at 5.6 days and 6 days, and it is likely to be similar in dogs. The only intervention between the pre-lipid serum sample and the post-lipid serum sample was the administration of ILE, and the serum desmethylbromethalin levels were reduced by 75% (from 4 ppb to 1 ppb) during this time. To the authors' knowledge, this is the first report describing treatment of bromethalin ingestion with ILE.

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Pilot, Randomized, Double-blind Trial To Study The Effect Of Parenteral Supplementation With Fish Oil Emulsion In The Nutritional Support Of Esophagectomized Patients

10.21203/rs.2.12187/v1 ◽

2019 ◽

Author(s):

Ana Suárez-Lledó ◽

Elisabet Leiva Badosa ◽

Josep M Llop Talaveron ◽

Monica Fernandez Alvarez ◽

Leandre Farran Teixidor ◽

...

Keyword(s):

Fatty Acids ◽

Enteral Nutrition ◽

Fish Oil ◽

Nutritional Support ◽

Lipid Emulsion ◽

Nutrition Support ◽

High Morbidity ◽

Lipid Emulsions ◽

Double Blind ◽

Enteral Nutrition Support

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.

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00303.2005 ◽

2006 ◽

Vol 290 (4) ◽

pp. E723-E730 ◽

Cited By ~ 39

Author(s):

Anne A. M. W. van Kempen ◽

Saskia N. van der Crabben ◽

Mariëtte T. Ackermans ◽

Erik Endert ◽

Joke H. Kok ◽

...

Keyword(s):

Fatty Acids ◽

Preterm Infants ◽

Lipid Emulsion ◽

Glucose Production ◽

The Other ◽

Lipid Emulsions ◽

Glucose Kinetics ◽

Intravenous Lipids ◽

Frequent Problem ◽

Stimulation Of

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.

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Decreased binding affinity of apolipoprotein C-II to Lipid Nano-Sphere (LNS) plays an important role in the plasma half-life and reduced hæmolytic activity

Journal of Drug Delivery Science and Technology ◽

10.1016/s1773-2247(04)50062-x ◽

2004 ◽

Vol 14 (5) ◽

pp. 345-352 ◽

Cited By ~ 2

Author(s):

J. Seki ◽

A. Saheki ◽

S. Sonoke ◽

H. Fukui ◽

T. Mayumi

Keyword(s):

Binding Affinity ◽

Half Life ◽

Haemolytic Activity ◽

Apolipoprotein C ◽

Plasma Half Life

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Effect of Nephrectomy and Enterectomy on Plasma Clearance of Intravenously Administered Dipeptides in Rats

Clinical Science ◽

10.1042/cs0520205 ◽

1977 ◽

Vol 52 (2) ◽

pp. 205-213 ◽

Cited By ~ 2

Author(s):

S. A. Adibi ◽

B. A. Krzysik

Keyword(s):

Small Intestine ◽

Renal Clearance ◽

Intestinal Mucosa ◽

Half Life ◽

Plasma Clearance ◽

Renal Cortex ◽

Plasma Concentrations ◽

Remarkable Effect ◽

Body Tissues ◽

Plasma Half Life

1. Sham-operated and bilaterally nephrectomized rats were injected intravenously with glycyl-l-leucine, glycylglycine and glycylsarcosine, and the concentrations of these dipeptides in plasma and muscle, liver, renal cortex (in the sham-operated rats) and intestinal mucosa at various intervals were determined. 2. Initially the plasma concentrations of glycyl-leucine and glycylglycine were higher in nephrectomized than in control rats but later the concentrations were similar in both groups of rats. The disappearance of these two dipeptides from plasma was almost complete within 20 min, and their plasma half-lives were not changed remarkably by nephrectomy. In contrast, nephrectomy markedly impaired disappearance of glycylsarcosine from plasma and prolonged its half-life from 7·6 min to 52·0 min. 3. Glycyl-leucine and glycylglycine were not detected in tissues of control rats injected with these dipeptides, but glycylsarcosine was recovered from all four tissues examined. Nephrectomy resulted in greater accumulations of glycylsarcosine in tissues and the appearance of glycylglycine in the remaining three tissues and glycyl-leucine in muscle. 4. Enterectomy did not have a remarkable effect on plasma half-life of glycylglycine but it allowed recovery of this dipeptide from renal cortex, liver and muscle. 5. It is concluded that kidneys and small intestine are involved in the disposition of circulating dipeptides, but in their absence other tissues may assume a greater role in this regard. However, renal clearance appears to be an important route for the disposition of dipeptides which are poorly hydrolysed by body tissues.

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Parenteral nutrition providing a restricted amount of linoleic acid in severely burned patients: a randomised double-blind study of an olive oil-based lipid emulsion v. medium/long-chain triacylglycerols

British Journal Of Nutrition ◽

10.1079/bjn20051467 ◽

2005 ◽

Vol 94 (2) ◽

pp. 221-230 ◽

Cited By ~ 59

Author(s):

A. García-de-Lorenzo ◽

R. Denia ◽

P. Atlan ◽

S. Martinez-Ratero ◽

A. Le Brun ◽

...

Keyword(s):

Fatty Acids ◽

Fatty Acid ◽

Linoleic Acid ◽

Liver Function ◽

Parenteral Nutrition ◽

Lipid Emulsion ◽

Liver Function Tests ◽

Lipid Emulsions ◽

Double Blind ◽

Long Chain

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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Covalent Complexes Between Low Molecular Weight Heparin Fragments and Antithrombin III – Inhibition Kinetics and Turnover Parameters

Thrombosis and Haemostasis ◽

10.1055/s-0038-1657333 ◽

1983 ◽

Vol 49 (02) ◽

pp. 109-115 ◽

Cited By ~ 4

Author(s):

M Hoylaerts ◽

E Holmer ◽

M de Mol ◽

D Collen

Keyword(s):

Molecular Weight ◽

Half Life ◽

Low Molecular Weight Heparin ◽

Antithrombin Iii ◽

Factor Xa ◽

Life Time ◽

Low Molecular Weight ◽

High Affinity ◽

Plasma Half Life ◽

Covalent Complex

SummaryTwo high affinity heparin fragments (A/r 4,300 and M, 3,200) were covalently coupled to antithrombin III (J. Biol. Chem. 1982; 257: 3401-3408) with an apparent 1:1 stoichiometry and a 30-35% yield.The purified covalent complexes inhibited factor Xa with second order rate constants very similar to those obtained for antithrombin III saturated with these heparin fragments and to that obtained for the covalent complex between antithrombin III and native high affinity heparin.The disappearance rates from plasma in rabbits of both low molecular weight heparin fragments and their complexes could adequately be represented by two-compartment mammillary models. The plasma half-life (t'/j) of both low Afr-heparin fragments was approximately 2.4 hr. Covalent coupling of the fragments to antithrombin III increased this half-life about 3.5 fold (t1/2 ≃ 7.7 hr), approaching that of free antithrombin III (t1/2 ≃ 11 ± 0.4 hr) and resulting in a 30fold longer life time of factor Xa inhibitory activity in plasma as compared to that of free intact heparin (t1/2 ≃ 0.25 ± 0.04 hr).

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Palmitic acid promotes resistin-induced insulin resistance and inflammation in SH-SY5Y human neuroblastoma

Scientific Reports ◽

10.1038/s41598-021-85018-7 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Hamza Amine ◽

Yacir Benomar ◽

Mohammed Taouis

Keyword(s):

Insulin Resistance ◽

Fatty Acids ◽

Palmitic Acid ◽

Lipid Rafts ◽

Acid Treatment ◽

Protective Action ◽

Saturated Fatty Acids ◽

Membrane Lipid ◽

Human Neuroblastoma ◽

Peripheral Tissues

AbstractSaturated fatty acids such as palmitic acid promote inflammation and insulin resistance in peripheral tissues, contrasting with the protective action of polyunsaturated fatty acids such docosahexaenoic acid. Palmitic acid effects have been in part attributed to its potential action through Toll-like receptor 4. Beside, resistin, an adipokine, also promotes inflammation and insulin resistance via TLR4. In the brain, palmitic acid and resistin trigger neuroinflammation and insulin resistance, but their link at the neuronal level is unknown. Using human SH-SY5Yneuroblastoma cell line we show that palmitic acid treatment impaired insulin-dependent Akt and Erk phosphorylation whereas DHA preserved insulin action. Palmitic acid up-regulated TLR4 as well as pro-inflammatory cytokines IL6 and TNFα contrasting with DHA effect. Similarly to palmitic acid, resistin treatment induced the up-regulation of IL6 and TNFα as well as NFκB activation. Importantly, palmitic acid potentiated the resistin-dependent NFkB activation whereas DHA abolished it. The recruitment of TLR4 to membrane lipid rafts was increased by palmitic acid treatment; this is concomitant with the augmentation of resistin-induced TLR4/MYD88/TIRAP complex formation mandatory for TLR4 signaling. In conclusion, palmitic acid increased TLR4 expression promoting resistin signaling through TLR4 up-regulation and its recruitment to membrane lipid rafts.

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