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Mark Puder - One of the best experts on this subject based on the ideXlab platform.
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use of fish oil intravenous lipid emulsions as monotherapy in the pediatric intestinal failure patient beyond the package insert
Nutrition in Clinical Practice, 2020Co-Authors: Kathleen M Gura, Kara L Calkins, Mark PuderAbstract:In July 2018, an intravenous lipid emulsion (ILE) composed of 100% fish oil (Omegaven, Fresenius Kabi, Bad Homburg, Germany) received Food and Drug Administration (FDA) approval as a source of fatty acids and calories for infants and children with parenteral nutrition-associated cholestasis. This soy-free fat source is rich in omega-3 fatty acids and alpha-tocopherol and contains few phytosterols. In comparison to conventional soybean oil ILE, this emulsion appears to be less hepatotoxic. The purpose of this paper is to guide the practitioner on the use of this alternative fat source in clinical practice and augment the material contained in the current package insert. This paper addresses various topics including the identification of which patients would benefit from fish oil ILE, dosing, administration, monitoring, potential adverse effects, and management strategies for fish oil ILE.
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use of fish oil intravenous lipid emulsions as monotherapy in the pediatric intestinal failure patient beyond the package insert
Nutrition in Clinical Practice, 2020Co-Authors: Kathleen M Gura, Kara L Calkins, Mark PuderAbstract:: In July 2018, an intravenous lipid emulsion (ILE) composed of 100% fish oil (Omegaven, Fresenius Kabi, Bad Homburg, Germany) received Food and Drug Administration (FDA) approval as a source of fatty acids and calories for infants and children with parenteral nutrition-associated cholestasis. This soy-free fat source is rich in ω-3 fatty acids and α-tocopherol and contains few phytosterols. In comparison to conventional soybean oil ILE, this emulsion appears to be less hepatotoxic. The purpose of this paper is to guide the practitioner on the use of this alternative fat source in clinical practice and augment the material contained in the current package insert. This paper addresses various topics including the identification of which patients would benefit from fish oil ILE, dosing, administration, monitoring, potential adverse effects, and management strategies for fish oil ILE.
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pretreatment with intravenous fish oil reduces hepatic ischemia reperfusion injury in a murine model
Surgery, 2018Co-Authors: Meredith A Baker, Kathleen M Gura, Prathima Nandivada, Paul Mitchell, Gillian L Fell, Amy Pan, Lorenzo Anezbustillos, Duy T Dao, Vania Nose, Mark PuderAbstract:Abstract Background Ischemia reperfusion injury is a barrier to liver surgery and transplantation, particularly for steatotic livers. The purpose of this study was to determine if pretreatment with a single dose of intravenous fish oil decreases hepatic ischemia reperfusion injury and improves recovery of injured livers. Methods Sixty adult male C57BL/6 mice received 1 g/kg intravenous fish oil (Omegaven, Fresenius Kabi) or isovolumetric 0.9% NaCl (saline) via tail vein 1 hour before 30 minutes of 70% hepatic ischemia. Animals were killed 4, 8, or 24 hours postreperfusion, and livers were harvested for histologic analysis. Results Four hours postreperfusion, saline-treated livers demonstrated marked ischemia diffusely around the central veins, while intravenous fish oil–treated livers demonstrated only patchy necrosis with intervening normal parenchyma. Eight hours postreperfusion, all livers demonstrated pale areas of cell loss with surrounding regenerating hepatocytes. Ki67 staining confirmed 14.4/10 high-powered field (95% confidence interval, 3.2–25.6) more regenerating hepatocytes around areas of necrosis in intravenous fish oil–treated livers. Twenty-four hours postreperfusion, all livers demonstrated patchy areas of necrosis, with an 89% (95% confidence interval, 85–92) decrease in the area of necrosis in intravenous fish oil–treated livers. Conclusion Intravenous fish oil treatment prior to hepatic ischemia reperfusion injury decreased the area of hepatic necrosis and increased hepatocyte regeneration compared to saline treatment in a mouse model.
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parenteral fish oil monotherapy in the management of patients with parenteral nutrition associated liver disease
Archives of Surgery, 2010Co-Authors: Vincent E De Meijer, Kathleen M Gura, Jonathan A Meisel, Mark PuderAbstract:Objectives To update knowledge on the management of parenteral nutrition–associated liver disease (PNALD) and to review the clinical data on the use of parenteral fish oil for reversal of PNALD. Data Sources A literature review was conducted by searching the MEDLINE database (May 1, 2009) using the keywords parenteral nutrition–associated liver disease, fish oil, omega-3, Omegaven , and lipid emulsion . Study Selection All articles reporting clinical cases with the use of parenteral fish oil for management of PNALD. Data Extraction Three reviewers independently analyzed the epidemiological, clinical, and treatment data of the articles. Data Synthesis Six case reports (10 patients) and 2 cohort studies (12 and 18 patients) were analyzed. Conclusions Fish oil–derived emulsions have been demonstrated to reverse preexisting PNALD and to prevent and treat essential fatty acid deficiency. Its ability to prevent PNALD is currently under investigation. Although the mechanism has yet to be fully understood, the advantages of fish oil–based lipid emulsions over soybean oil–based lipid emulsions seen to date suggest that fish oil–based emulsions would be better suited for use in long-term parenteral nutrition.
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prevention of parenteral nutrition associated liver disease role of omega 3 fish oil
Current Opinion in Organ Transplantation, 2010Co-Authors: Erica M Fallon, Mark PuderAbstract:Purpose of review Parenteral nutrition-associated liver disease (PNALD) is the most severe complication of long-term parenteral nutrition. Its cause remains unclear, although recent studies suggest that the omega-6 polyunsaturated fatty acids in plant oil-based lipid emulsions and the associated phytosterols contribute to the development of hepatotoxicity. In contrast, fish oil-based lipid emulsions are composed mainly of omega-3 polyunsaturated fatty acids and are hypothesized to be hepatoprotective. This review will discuss fish oil-based lipid emulsions in the prevention of PNALD. Recent findings In several animal models of PNALD, the use of an intravenous fish oil-based lipid emulsion improved parenteral nutrition-associated cholestasis without resultant essential fatty acid deficiency or growth impairment. Following these results and preliminary human data, an open trial for compassionate use was initiated, followed by a randomized controlled trial to evaluate the current management of pediatric PNALD. To date, at the author's institution, more than 130 children with PNALD have been treated with Omegaven, a fish oil-based emulsion, with improved liver function among most patients. Summary PNALD remains the most severe complication of long-term parenteral nutrition with an unclear pathophysiology. However, the use of a fish oil-based emulsion appears efficacious and hepatoprotective.
Martin Hersberger - One of the best experts on this subject based on the ideXlab platform.
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choice of lipid emulsion determines inflammation of the gut liver axis incretin profile and insulin signaling in a murine model of total parenteral nutrition
Molecular Nutrition & Food Research, 2021Co-Authors: Phinghow Lou, Eliana Lucchinetti, Martin Hersberger, Paulina Wawrzyniak, Yasser Morsy, Marcin Wawrzyniak, Michael Scharl, Stefanie D Kramer, Gerhard RoglerAbstract:SCOPE: The aim of this study was to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), i.e. n-3 fatty acid-based Omegaven versus n-6 fatty acid-based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. METHODS AND RESULTS: Jugular vein catheters (JVC) were placed in C57BL/6 mice and used for TPN for seven days. Mice were randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL-TPN, no chow), an Omegaven group (OV-TPN, no chow), or a chow only group (without JVC). Both TPN elicited higher abundance of lipopolysaccharide binding protein in the liver, but only IL-TPN increased interleukin-6 and interferon-I³, while OV-TPN reduced interleukin-4, monocyte chemoattractant protein-1, and interleukin-1E. Insulin plasma concentrations were higher in both TPN, while glucagon and GLP1 were higher in IL-TPN. Gluconeogenesis was increased in IL-TPN and the nuclear profile of key metabolic transcription factors showed a liver-protective phenotype in OV-TPN. OV-TPN increased insulin sensitivity in the liver and skeletal muscle. CONCLUSIONS: OV-TPN as opposed to IL-TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by "re-sensitizing" the liver and skeletal muscle to insulin. This article is protected by copyright. All rights reserved.
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diabetic rat hearts show more favorable metabolic adaptation to Omegaven containing high amounts of n3 fatty acids than intralipid containing n6 fatty acids
Anesthesia & Analgesia, 2020Co-Authors: Eliana Lucchinetti, Phinghow Lou, Martin Hersberger, Alexander S Clanachan, Michael ZauggAbstract:Background While Omegaven, an omega-3 (n3) fatty acid-based lipid emulsion, fosters insulin signaling in healthy hearts, it is unknown whether beneficial metabolic effects occur in insulin-resistant diabetic hearts. Methods Diabetic hearts from fructose-fed Sprague-Dawley rats were perfused in the working mode for 90 minutes in the presence of 11 mM glucose and 1.2 mM palmitate bound to albumin, the first 30 minutes without insulin followed by 60 minutes with insulin (50 mU/L). Hearts were randomly allocated to Intralipid (25 and 100 µM), Omegaven (25 and 100 µM), or no emulsion (insulin alone) for 60 minutes. Glycolysis, glycogen synthesis, and glucose oxidation were measured with the radioactive tracers [5-H]glucose and [U-C]glucose. Central carbon metabolites, acyl-coenzyme A species (acyl-CoAs), ketoacids, purines, phosphocreatine, acylcarnitines, and acyl composition of phospholipids were measured with mass spectrometry. Results Diabetic hearts showed no response to insulin with regard to glycolytic flux, consistent with insulin resistance. Addition of either lipid emulsion did not alter this response but unexpectedly increased glucose oxidation (ratio of treatment/baseline, ie, fold change): no insulin 1.3 (0.3) [mean (standard deviation)], insulin alone 1.4 (0.4), insulin + 25 µM Intralipid 1.8 (0.5), insulin + 100 µM Intralipid 2.2 (0.4), P Conclusions Omegaven is the preferred lipid emulsion for insulin-resistant diabetic hearts.
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lipid emulsion containing high amounts of n3 fatty acids Omegaven as opposed to n6 fatty acids intralipid preserves insulin signaling and glucose uptake in perfused rat hearts
Anesthesia & Analgesia, 2020Co-Authors: Phinghow Lou, Eliana Lucchinetti, Martin Hersberger, Alexander S Clanachan, Michael ZauggAbstract:BACKGROUND:It is currently unknown whether acute exposure to n3 fatty acid–containing fish oil–based lipid emulsion Omegaven as opposed to the n6 fatty acid–containing soybean oil–based lipid emulsion Intralipid is more favorable in terms of insulin signaling and glucose uptake in the intact beating
Kathleen M Gura - One of the best experts on this subject based on the ideXlab platform.
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use of fish oil intravenous lipid emulsions as monotherapy in the pediatric intestinal failure patient beyond the package insert
Nutrition in Clinical Practice, 2020Co-Authors: Kathleen M Gura, Kara L Calkins, Mark PuderAbstract:In July 2018, an intravenous lipid emulsion (ILE) composed of 100% fish oil (Omegaven, Fresenius Kabi, Bad Homburg, Germany) received Food and Drug Administration (FDA) approval as a source of fatty acids and calories for infants and children with parenteral nutrition-associated cholestasis. This soy-free fat source is rich in omega-3 fatty acids and alpha-tocopherol and contains few phytosterols. In comparison to conventional soybean oil ILE, this emulsion appears to be less hepatotoxic. The purpose of this paper is to guide the practitioner on the use of this alternative fat source in clinical practice and augment the material contained in the current package insert. This paper addresses various topics including the identification of which patients would benefit from fish oil ILE, dosing, administration, monitoring, potential adverse effects, and management strategies for fish oil ILE.
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use of fish oil intravenous lipid emulsions as monotherapy in the pediatric intestinal failure patient beyond the package insert
Nutrition in Clinical Practice, 2020Co-Authors: Kathleen M Gura, Kara L Calkins, Mark PuderAbstract:: In July 2018, an intravenous lipid emulsion (ILE) composed of 100% fish oil (Omegaven, Fresenius Kabi, Bad Homburg, Germany) received Food and Drug Administration (FDA) approval as a source of fatty acids and calories for infants and children with parenteral nutrition-associated cholestasis. This soy-free fat source is rich in ω-3 fatty acids and α-tocopherol and contains few phytosterols. In comparison to conventional soybean oil ILE, this emulsion appears to be less hepatotoxic. The purpose of this paper is to guide the practitioner on the use of this alternative fat source in clinical practice and augment the material contained in the current package insert. This paper addresses various topics including the identification of which patients would benefit from fish oil ILE, dosing, administration, monitoring, potential adverse effects, and management strategies for fish oil ILE.
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pretreatment with intravenous fish oil reduces hepatic ischemia reperfusion injury in a murine model
Surgery, 2018Co-Authors: Meredith A Baker, Kathleen M Gura, Prathima Nandivada, Paul Mitchell, Gillian L Fell, Amy Pan, Lorenzo Anezbustillos, Duy T Dao, Vania Nose, Mark PuderAbstract:Abstract Background Ischemia reperfusion injury is a barrier to liver surgery and transplantation, particularly for steatotic livers. The purpose of this study was to determine if pretreatment with a single dose of intravenous fish oil decreases hepatic ischemia reperfusion injury and improves recovery of injured livers. Methods Sixty adult male C57BL/6 mice received 1 g/kg intravenous fish oil (Omegaven, Fresenius Kabi) or isovolumetric 0.9% NaCl (saline) via tail vein 1 hour before 30 minutes of 70% hepatic ischemia. Animals were killed 4, 8, or 24 hours postreperfusion, and livers were harvested for histologic analysis. Results Four hours postreperfusion, saline-treated livers demonstrated marked ischemia diffusely around the central veins, while intravenous fish oil–treated livers demonstrated only patchy necrosis with intervening normal parenchyma. Eight hours postreperfusion, all livers demonstrated pale areas of cell loss with surrounding regenerating hepatocytes. Ki67 staining confirmed 14.4/10 high-powered field (95% confidence interval, 3.2–25.6) more regenerating hepatocytes around areas of necrosis in intravenous fish oil–treated livers. Twenty-four hours postreperfusion, all livers demonstrated patchy areas of necrosis, with an 89% (95% confidence interval, 85–92) decrease in the area of necrosis in intravenous fish oil–treated livers. Conclusion Intravenous fish oil treatment prior to hepatic ischemia reperfusion injury decreased the area of hepatic necrosis and increased hepatocyte regeneration compared to saline treatment in a mouse model.
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parenteral fish oil monotherapy in the management of patients with parenteral nutrition associated liver disease
Archives of Surgery, 2010Co-Authors: Vincent E De Meijer, Kathleen M Gura, Jonathan A Meisel, Mark PuderAbstract:Objectives To update knowledge on the management of parenteral nutrition–associated liver disease (PNALD) and to review the clinical data on the use of parenteral fish oil for reversal of PNALD. Data Sources A literature review was conducted by searching the MEDLINE database (May 1, 2009) using the keywords parenteral nutrition–associated liver disease, fish oil, omega-3, Omegaven , and lipid emulsion . Study Selection All articles reporting clinical cases with the use of parenteral fish oil for management of PNALD. Data Extraction Three reviewers independently analyzed the epidemiological, clinical, and treatment data of the articles. Data Synthesis Six case reports (10 patients) and 2 cohort studies (12 and 18 patients) were analyzed. Conclusions Fish oil–derived emulsions have been demonstrated to reverse preexisting PNALD and to prevent and treat essential fatty acid deficiency. Its ability to prevent PNALD is currently under investigation. Although the mechanism has yet to be fully understood, the advantages of fish oil–based lipid emulsions over soybean oil–based lipid emulsions seen to date suggest that fish oil–based emulsions would be better suited for use in long-term parenteral nutrition.
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A metabolomic analysis of two intravenous lipid emulsions in a murine model.
Public Library of Science (PLoS), 2024Co-Authors: Brian T Kalish, Kathleen M Gura, Bruce R Bistrian, Mark PuderAbstract:Parenteral nutrition (PN), including intravenous lipid administration, is a life-saving therapy but can be complicated by cholestasis and liver disease. The administration of intravenous soy bean oil (SO) has been associated with the development of liver disease, while the administration of intravenous fish oil (FO) has been associated with the resolution of liver disease. The biochemical mechanism of this differential effect is unclear. This study compares SO and FO lipid emulsions in a murine model of hepatic steatosis, one of the first hits in PN-associated liver disease.We established a murine model of hepatic steatosis in which liver injury is induced by orally feeding mice a PN solution. C57BL/6J mice were randomized to receive PN alone (a high carbohydrate diet (HCD)), PN plus intravenous FO (Omegaven®; Fresenius Kabi AG, Bad Homburg VDH, Germany), PN plus intravenous SO (Intralipid®; Fresenius Kabi AG, Bad Homburg v.d.H., Germany, for Baxter Healthcare, Deerfield, IL), or a chow diet. After 19 days, liver tissue was harvested from all animals and subjected to metabolomic profiling.The administration of an oral HCD without lipid induced profound hepatic steatosis. SO was associated with macro- and microvesicular hepatic steatosis, while FO largely prevented the development of steatosis. 321 detectable compounds were identified in the metabolomic analysis. HCD induced de novo fatty acid synthesis and oxidative stress. Both FO and SO relieved some of the metabolic shift towards de novo lipogenesis, but FO offered additional advantages in terms of lipid peroxidation and the generation of inflammatory precursors.Improved lipid metabolism combined with reduced oxidative stress may explain the protective effect offered by intravenous FO in vivo
Michael Zaugg - One of the best experts on this subject based on the ideXlab platform.
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diabetic rat hearts show more favorable metabolic adaptation to Omegaven containing high amounts of n3 fatty acids than intralipid containing n6 fatty acids
Anesthesia & Analgesia, 2020Co-Authors: Eliana Lucchinetti, Phinghow Lou, Martin Hersberger, Alexander S Clanachan, Michael ZauggAbstract:Background While Omegaven, an omega-3 (n3) fatty acid-based lipid emulsion, fosters insulin signaling in healthy hearts, it is unknown whether beneficial metabolic effects occur in insulin-resistant diabetic hearts. Methods Diabetic hearts from fructose-fed Sprague-Dawley rats were perfused in the working mode for 90 minutes in the presence of 11 mM glucose and 1.2 mM palmitate bound to albumin, the first 30 minutes without insulin followed by 60 minutes with insulin (50 mU/L). Hearts were randomly allocated to Intralipid (25 and 100 µM), Omegaven (25 and 100 µM), or no emulsion (insulin alone) for 60 minutes. Glycolysis, glycogen synthesis, and glucose oxidation were measured with the radioactive tracers [5-H]glucose and [U-C]glucose. Central carbon metabolites, acyl-coenzyme A species (acyl-CoAs), ketoacids, purines, phosphocreatine, acylcarnitines, and acyl composition of phospholipids were measured with mass spectrometry. Results Diabetic hearts showed no response to insulin with regard to glycolytic flux, consistent with insulin resistance. Addition of either lipid emulsion did not alter this response but unexpectedly increased glucose oxidation (ratio of treatment/baseline, ie, fold change): no insulin 1.3 (0.3) [mean (standard deviation)], insulin alone 1.4 (0.4), insulin + 25 µM Intralipid 1.8 (0.5), insulin + 100 µM Intralipid 2.2 (0.4), P Conclusions Omegaven is the preferred lipid emulsion for insulin-resistant diabetic hearts.
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lipid emulsion containing high amounts of n3 fatty acids Omegaven as opposed to n6 fatty acids intralipid preserves insulin signaling and glucose uptake in perfused rat hearts
Anesthesia & Analgesia, 2020Co-Authors: Phinghow Lou, Eliana Lucchinetti, Martin Hersberger, Alexander S Clanachan, Michael ZauggAbstract:BACKGROUND:It is currently unknown whether acute exposure to n3 fatty acid–containing fish oil–based lipid emulsion Omegaven as opposed to the n6 fatty acid–containing soybean oil–based lipid emulsion Intralipid is more favorable in terms of insulin signaling and glucose uptake in the intact beating
Phinghow Lou - One of the best experts on this subject based on the ideXlab platform.
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choice of lipid emulsion determines inflammation of the gut liver axis incretin profile and insulin signaling in a murine model of total parenteral nutrition
Molecular Nutrition & Food Research, 2021Co-Authors: Phinghow Lou, Eliana Lucchinetti, Martin Hersberger, Paulina Wawrzyniak, Yasser Morsy, Marcin Wawrzyniak, Michael Scharl, Stefanie D Kramer, Gerhard RoglerAbstract:SCOPE: The aim of this study was to test whether the choice of the lipid emulsion in total parenteral nutrition (TPN), i.e. n-3 fatty acid-based Omegaven versus n-6 fatty acid-based Intralipid, determines inflammation in the liver, the incretin profile, and insulin resistance. METHODS AND RESULTS: Jugular vein catheters (JVC) were placed in C57BL/6 mice and used for TPN for seven days. Mice were randomized into a saline group (saline infusion with oral chow), an Intralipid group (IL-TPN, no chow), an Omegaven group (OV-TPN, no chow), or a chow only group (without JVC). Both TPN elicited higher abundance of lipopolysaccharide binding protein in the liver, but only IL-TPN increased interleukin-6 and interferon-I³, while OV-TPN reduced interleukin-4, monocyte chemoattractant protein-1, and interleukin-1E. Insulin plasma concentrations were higher in both TPN, while glucagon and GLP1 were higher in IL-TPN. Gluconeogenesis was increased in IL-TPN and the nuclear profile of key metabolic transcription factors showed a liver-protective phenotype in OV-TPN. OV-TPN increased insulin sensitivity in the liver and skeletal muscle. CONCLUSIONS: OV-TPN as opposed to IL-TPN mitigates inflammation in the liver and reduces the negative metabolic effects of hyperinsulinemia and hyperglucagonemia by "re-sensitizing" the liver and skeletal muscle to insulin. This article is protected by copyright. All rights reserved.
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diabetic rat hearts show more favorable metabolic adaptation to Omegaven containing high amounts of n3 fatty acids than intralipid containing n6 fatty acids
Anesthesia & Analgesia, 2020Co-Authors: Eliana Lucchinetti, Phinghow Lou, Martin Hersberger, Alexander S Clanachan, Michael ZauggAbstract:Background While Omegaven, an omega-3 (n3) fatty acid-based lipid emulsion, fosters insulin signaling in healthy hearts, it is unknown whether beneficial metabolic effects occur in insulin-resistant diabetic hearts. Methods Diabetic hearts from fructose-fed Sprague-Dawley rats were perfused in the working mode for 90 minutes in the presence of 11 mM glucose and 1.2 mM palmitate bound to albumin, the first 30 minutes without insulin followed by 60 minutes with insulin (50 mU/L). Hearts were randomly allocated to Intralipid (25 and 100 µM), Omegaven (25 and 100 µM), or no emulsion (insulin alone) for 60 minutes. Glycolysis, glycogen synthesis, and glucose oxidation were measured with the radioactive tracers [5-H]glucose and [U-C]glucose. Central carbon metabolites, acyl-coenzyme A species (acyl-CoAs), ketoacids, purines, phosphocreatine, acylcarnitines, and acyl composition of phospholipids were measured with mass spectrometry. Results Diabetic hearts showed no response to insulin with regard to glycolytic flux, consistent with insulin resistance. Addition of either lipid emulsion did not alter this response but unexpectedly increased glucose oxidation (ratio of treatment/baseline, ie, fold change): no insulin 1.3 (0.3) [mean (standard deviation)], insulin alone 1.4 (0.4), insulin + 25 µM Intralipid 1.8 (0.5), insulin + 100 µM Intralipid 2.2 (0.4), P Conclusions Omegaven is the preferred lipid emulsion for insulin-resistant diabetic hearts.
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lipid emulsion containing high amounts of n3 fatty acids Omegaven as opposed to n6 fatty acids intralipid preserves insulin signaling and glucose uptake in perfused rat hearts
Anesthesia & Analgesia, 2020Co-Authors: Phinghow Lou, Eliana Lucchinetti, Martin Hersberger, Alexander S Clanachan, Michael ZauggAbstract:BACKGROUND:It is currently unknown whether acute exposure to n3 fatty acid–containing fish oil–based lipid emulsion Omegaven as opposed to the n6 fatty acid–containing soybean oil–based lipid emulsion Intralipid is more favorable in terms of insulin signaling and glucose uptake in the intact beating
