scholarly journals Differential and shared effects of eicosapentaenoic acid and docosahexaenoic acid on serum metabolome in subjects with chronic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Wan-Chi Chang ◽  
Jisun So ◽  
Stefania Lamon-Fava
Keyword(s):  
Metabolic Syndrome ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Chronic Inflammation ◽  
Cell Function ◽  
Tca Cycle ◽  
Differential Effects ◽  
Epa And Dha ◽  
The Tca Cycle ◽  
Tca Cycle Intermediates

AbstractThe omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) affect cell function and metabolism, but the differential effects of EPA and DHA are not known. In a randomized, controlled, double-blind, crossover study, we assessed the effects of 10-week supplementation with EPA-only and DHA-only (3 g/d), relative to a 4-week lead-in phase of high oleic acid sunflower oil (3 g/day, defined as baseline), on fasting serum metabolites in 21 subjects (9 men and 12 post-menopausal women) with chronic inflammation and some characteristics of metabolic syndrome. Relative to baseline, EPA significantly lowered the tricarboxylic acid (TCA) cycle intermediates fumarate and α-ketoglutarate and increased glucuronate, UDP-glucuronate, and non-esterified DHA. DHA significantly lowered the TCA cycle intermediates pyruvate, citrate, isocitrate, fumarate, α-ketoglutarate, and malate, and increased succinate and glucuronate. Pathway analysis showed that both EPA and DHA significantly affected the TCA cycle, the interconversion of pentose and glucuronate, and alanine, and aspartate and glutamate pathways (FDR < 0.05) and that DHA had a significantly greater effect on the TCA cycle than EPA. Our results indicate that EPA and DHA exhibit both common and differential effects on cell metabolism in subjects with chronic inflammation and some key aspects of metabolic syndrome.

scholarly journals Differential Effects of Eicosapentaenoic Acid and Docosahexaenoic Acid on Serum Metabolome

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 302-302
Author(s):  
Wan Chi Chang ◽  
Jisun So ◽  
Stefania Lamon-Fava
Keyword(s):  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Mixed Model ◽  
Linear Mixed Model ◽  
Glucuronic Acid ◽  
Tca Cycle ◽  
Gas Chromatography Mass Spectrometry ◽  
Differential Effects ◽  
Epa And Dha ◽  
The Tca Cycle

Abstract Objectives The omega-3 fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been shown to have shared and independent effects on inflammation and on lipid and glucose metabolism. However, the differential effects of EPA and DHA on serum metabolome remain elusive in humans. Methods Twenty-one subjects (9 men and 12 women, 50–75 y) with chronic inflammation (C reactive protein &gt; 2 μg/mL) were enrolled in a randomized, controlled crossover trial consisting of a 4-week lead-in phase (high oleic sunflower oil, 3 g/d; baseline) followed by randomization to two sequential 10-week supplementation phases with pure EPA and DHA (3 g/d each) separated by a 10-week washout. Primary metabolites (n = 129) were measured in fasting serum samples by gas chromatography-mass spectrometry. Linear-mixed model was created to compare changes in metabolites by EPA and DHA relative to baseline. Pathway analysis (MetaboAnalyst 4.0, https://www.metaboanalyst.ca) was performed to identify the biological pathways associated with affected metabolites. Results DHA altered a greater number of metabolites than EPA (19 vs 11). Both EPA and DHA significantly lowered constitutive metabolites of the TCA cycle and the alanine, aspartate and glutamate metabolism pathway, with DHA showing a greater reduction than EPA. EPA significantly increased UDP-glucuronic acid and glucuronic acid, and DHA increased only glucuronic acid, thus affecting pathways where these metabolites play key roles (ascorbate and aldarate metabolism; pentose and glucuronate interconversions). Conclusions DHA affected more metabolites than EPA. The greater impact of DHA on the TCA cycle and the larger effect of EPA on the glucose-derived glucuronic acid-related pathways suggest their differential ability to modulate metabolic pathways. Funding Sources Grant number: 2015–67,017-23,142 from the National Institute of Food and Agriculture, U.S. Department Of Agriculture.

scholarly journals Microalgae n-3 PUFAs Production and Use in Food and Feed Industries

Marine Drugs ◽  
2021 ◽  
Vol 19 (2) ◽  
pp. 113
Author(s):  
Marine Remize ◽  
Yves Brunel ◽  
Joana L. Silva ◽  
Jean-Yves Berthon ◽  
Edith Filaire
Keyword(s):  
Fatty Acids ◽  
Global Warming ◽  
Docosahexaenoic Acid ◽  
Polyunsaturated Fatty Acids ◽  
Eicosapentaenoic Acid ◽  
Human Health ◽  
Current Knowledge ◽  
Epa And Dha ◽  
Anti Cancer ◽  
Food And Feed

N-3 polyunsaturated fatty acids (n-3 PUFAs), and especially eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), are essential compounds for human health. They have been proven to act positively on a panel of diseases and have interesting anti-oxidative, anti-inflammatory or anti-cancer properties. For these reasons, they are receiving more and more attention in recent years, especially future food or feed development. EPA and DHA come mainly from marine sources like fish or seaweed. Unfortunately, due to global warming, these compounds are becoming scarce for humans because of overfishing and stock reduction. Although increasing in recent years, aquaculture appears insufficient to meet the increasing requirements of these healthy molecules for humans. One alternative resides in the cultivation of microalgae, the initial producers of EPA and DHA. They are also rich in biochemicals with interesting properties. After defining macro and microalgae, this review synthesizes the current knowledge on n-3 PUFAs regarding health benefits and the challenges surrounding their supply within the environmental context. Microalgae n-3 PUFA production is examined and its synthesis pathways are discussed. Finally, the use of EPA and DHA in food and feed is investigated. This work aims to define better the issues surrounding n-3 PUFA production and supply and the potential of microalgae as a sustainable source of compounds to enhance the food and feed of the future.

scholarly journals STUDY ON THE THERMAL STABILITY OF EPA AND DHA IN MUJAHIR (Oreochromis mossambicus) FISH OIL

2010 ◽  
Vol 5 (2) ◽  
pp. 152-155 ◽  
Author(s):  
Ngatidjo Hadipranoto
Keyword(s):  
Gas Chromatography ◽  
Fatty Acid ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Fish Oil ◽  
Oreochromis Mossambicus ◽  
Heating Process ◽  
Fresh Water Fish ◽  
Epa And Dha ◽  
Indirect Heating

EPA (Eicosapentaenoic acid) and DHA (Docosahexaenoic acid) content in common fresh water fish : mujahir (Oreochromis mossambicus) after indirect heating were analysed. The aims of this study were to determine the effect of indirect heating process and α-tocopherol additions on both fatty acid stability.Lipids content in the mujahir fillets were extracted by Folch method using chloroform-metanol (2:1) mixture. Fatty acids in fish oil were converted to fatty acid methyl esters and then injected into gas chromatography to determine the EPA and DHA concentration. Operating condition of gas chromatography were programmed as follows: injection port temperature at 270 oC, detector at 280 oC, initial column temperature at 200 oC, and the final at 280 oC, the carrier gas was helium with flow rate of 10 ml per minute and temperature of column was increased gradually at 10 oC per minute. The effect of α-tocopherol addition on the stability of EPA and DHA was studied by adding α-tocopherol at 50 to 200 mg per kilogram sample before indirect heating process was carried out.The analysis of mujahir fish oil showed that the content of EPA and DHA in 100 grams fresh sample was 105 and 406,5 mg respectivelly. Indirect heating caused the EPA and DHA content decreased significantly. The addition of α-tocopherol results in a positive corelation between α-tocopherol concentration added and the decrease of EPA and DHA content during the heating process.   Keywords: fatty acid, eicosapentaenoic acid, docosahexaenoic acid

Glutamate availability is important in intramuscular amino acid metabolism and TCA cycle intermediates but does not affect peak oxidative metabolism

2008 ◽  
Vol 105 (2) ◽  
pp. 547-554 ◽  
Author(s):  
M. Mourtzakis ◽  
T. E. Graham ◽  
J. González-Alonso ◽  
B. Saltin
Keyword(s):  
Oxidative Metabolism ◽  
Acid Metabolism ◽  
Glutamate Uptake ◽  
Knee Extensor ◽  
Tca Cycle ◽  
Peak Oxygen Consumption ◽  
Peak Exercise ◽  
Early Exercise ◽  
The Tca Cycle ◽  
Tca Cycle Intermediates

Muscle glutamate is central to reactions producing 2-oxoglutarate, a tricarboxylic acid (TCA) cycle intermediate that essentially expands the TCA cycle intermediate pool during exercise. Paradoxically, muscle glutamate drops ∼40–80% with the onset of exercise and 2-oxoglutarate declines in early exercise. To investigate the physiological relationship between glutamate, oxidative metabolism, and TCA cycle intermediates (i.e., fumarate, malate, 2-oxoglutarate), healthy subjects trained (T) the quadriceps of one thigh on the single-legged knee extensor ergometer (1 h/day at 70% maximum workload for 5 days/wk), while their contralateral quadriceps remained untrained (UT). After 5 wk of training, peak oxygen consumption (V̇o2peak) in the T thigh was greater than that in the UT thigh ( P < 0.05); V̇o2peak was not different between the T and UT thighs with glutamate infusion. Peak exercise under control conditions revealed a greater glutamate uptake in the T thigh compared with rest (7.3 ± 3.7 vs. 1.0 ± 0.1 μmol·min−1·kg wet wt−1, P < 0.05) without increase in TCA cycle intermediates. In the UT thigh, peak exercise (vs. rest) induced an increase in fumarate (0.33 ± 0.07 vs. 0.02 ± 0.01 mmol/kg dry wt (dw), P < 0.05) and malate (2.2 ± 0.4 vs. 0.5 ± 0.03 mmol/kg dw, P < 0.05) and a decrease in 2-oxoglutarate (12.2 ± 1.6 vs. 32.4 ± 6.8 μmol/kg dw, P < 0.05). Overall, glutamate infusion increased arterial glutamate ( P < 0.05) and maintained this increase. Glutamate infusion coincided with elevated fumarate and malate ( P < 0.05) and decreased 2-oxoglutarate ( P < 0.05) at peak exercise relative to rest in the T thigh; there were no further changes in the UT thigh. Although glutamate may have a role in the expansion of the TCA cycle, glutamate and TCA cycle intermediates do not directly affect V̇o2peak in either trained or untrained muscle.

scholarly journals Ammonia inhibits energy metabolism in astrocytes in a rapid and glutamate dehydrogenase 2-dependent manner

2020 ◽  
Vol 13 (10) ◽  
pp. dmm047134
Author(s):  
Leonie Drews ◽  
Marcel Zimmermann ◽  
Philipp Westhoff ◽  
Dominik Brilhaus ◽  
Rebecca E. Poss ◽  
...  
Keyword(s):  
Amino Acids ◽  
Energy Metabolism ◽  
Glutamate Dehydrogenase ◽  
Mitochondrial Respiration ◽  
Tca Cycle ◽  
Dependent Manner ◽  
Independent Manner ◽  
The Tca Cycle ◽  
Branched Chain ◽  
Tca Cycle Intermediates

ABSTRACTAstrocyte dysfunction is a primary factor in hepatic encephalopathy (HE) impairing neuronal activity under hyperammonemia. In particular, the early events causing ammonia-induced toxicity to astrocytes are not well understood. Using established cellular HE models, we show that mitochondria rapidly undergo fragmentation in a reversible manner upon hyperammonemia. Further, in our analyses, within a timescale of minutes, mitochondrial respiration and glycolysis were hampered, which occurred in a pH-independent manner. Using metabolomics, an accumulation of glucose and numerous amino acids, including branched chain amino acids, was observed. Metabolomic tracking of 15N-labeled ammonia showed rapid incorporation of 15N into glutamate and glutamate-derived amino acids. Downregulating human GLUD2 [encoding mitochondrial glutamate dehydrogenase 2 (GDH2)], inhibiting GDH2 activity by SIRT4 overexpression, and supplementing cells with glutamate or glutamine alleviated ammonia-induced inhibition of mitochondrial respiration. Metabolomic tracking of 13C-glutamine showed that hyperammonemia can inhibit anaplerosis of tricarboxylic acid (TCA) cycle intermediates. Contrary to its classical anaplerotic role, we show that, under hyperammonemia, GDH2 catalyzes the removal of ammonia by reductive amination of α-ketoglutarate, which efficiently and rapidly inhibits the TCA cycle. Overall, we propose a critical GDH2-dependent mechanism in HE models that helps to remove ammonia, but also impairs energy metabolism in mitochondria rapidly.

Relationship between fish oil intake by dairy cows and the yield of eicosapentaenoic acid and docosahexaenoic acid in their milk

2001 ◽  
Vol 2001 ◽  
pp. 199-199 ◽  
Author(s):  
C. Rymer ◽  
C. Dyer ◽  
D.I. Givens ◽  
R. Allison
Keyword(s):  
Fatty Acids ◽  
Docosahexaenoic Acid ◽  
Eicosapentaenoic Acid ◽  
Fish Oil ◽  
Dairy Cows ◽  
Fish Consumption ◽  
Essential Fatty Acids ◽  
Epa And Dha ◽  
The Uk

The dietary essential fatty acids eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) are predominantly found in fish oil, but fish consumption in the UK is low. Increasing the yield of EPA and DHA in cows’ milk would increase human intakes of EPA and DHA, and this can be achieved by including fish oil in cows’ diets. However, because EPA and DHA are susceptible to rumen biohydrogenation, their transfer efficiency into milk is low.In vitroobservations by Gulatiet al. (1999) suggested that if the concentration of fish oil in the rumen exceeded 1 mg/ml, EPA and DHA were not hydrogenated. The objectives of this study were therefore to determine the relationships between fish oil intake by dairy cows, and the probable concentrations of fish oil in the cows’ rumen, with the yield of EPA and DHA in their milk.

scholarly journals Detrimental actions of metabolic syndrome risk factor, homocysteine, on pancreatic β-cell glucose metabolism and insulin secretion

2006 ◽  
Vol 189 (2) ◽  
pp. 301-310 ◽  
Author(s):  
S Patterson ◽  
P R Flatt ◽  
L Brennan ◽  
P Newsholme ◽  
N H McClenaghan
Keyword(s):  
Metabolic Syndrome ◽  
Insulin Secretion ◽  
Glucose Metabolism ◽  
Insulin Release ◽  
Cell Function ◽  
Tca Cycle ◽  
Gastric Inhibitory Polypeptide ◽  
Β Cell ◽  
The Metabolic Syndrome ◽  
Cell Glucose

Elevated plasma homocysteine has been reported in individuals with diseases of the metabolic syndrome including vascular disease and insulin resistance. As homocysteine exerts detrimental effects on endothelial and neuronal cells, this study investigated effects of acute homocysteine exposure on β-cell function and insulin secretion using clonal BRIN-BD11 β-cells. Acute insulin release studies in the presence of various test reagents were performed using monolayers of BRIN-BD11 cells and samples assayed by insulin radioimmunoassay. Cellular glucose metabolism was assessed by nuclear magnetic resonance (NMR) analysis following 60-min exposure of BRIN-BD11 cell monolayers to glucose in either the absence or presence of homocysteine. Homocysteine dose-dependently inhibited insulin release at moderate and stimulatory glucose concentrations. This inhibitory effect was reversible at all but the highest concentration of homocysteine. 13C-glucose NMR demonstrated decreased labelling of glutamate from glucose at positions C2, C3 and C4, indicating that the tricarboxylic acid (TCA) cycle-dependent glucose metabolism was reduced in the presence of homocysteine. Homocysteine also dose-dependently inhibited insulinotropic responses to a range of glucose-dependent secretagogues including nutrients (alanine, arginine, 2-ketoisocaproate), hormones (glucagon-like peptide-1 (7–36)amide, gastric inhibitory polypeptide and cholecystokinin-8), neurotransmitter (carbachol), drug (tolbutamide) as well as a depolarising concentration of KCl or elevated Ca2+. Insulin secretion induced by activation of adenylate cyclase and protein kinase C pathways with forskolin and phorbol 12-myristate 13-acetate were also inhibited by homocysteine. These effects were not associated with any adverse action on cellular insulin content or cell viability, and there was no increase in apoptosis/necrosis following exposure to homocysteine. These data indicate that homocysteine impairs insulin secretion through alterations in β-cell glucose metabolism and generation of key stimulus-secretion coupling factors. The participation of homocysteine in possible β-cell demise merits further investigation.

scholarly journals Evidence for reverse flux through pyruvate kinase in skeletal muscle

2009 ◽  
Vol 296 (4) ◽  
pp. E748-E757 ◽  
Author(s):  
Eunsook S. Jin ◽  
A. Dean Sherry ◽  
Craig R. Malloy
Keyword(s):  
Skeletal Muscle ◽  
Glucose Production ◽  
Tca Cycle ◽  
Hepatic Glycogen ◽  
Direct Transfer ◽  
The Tca Cycle ◽  
Tca Cycle Intermediates ◽  
Minced Muscle ◽  
Labeling Pattern

Conversion of lactate to glucose was examined in myotubes, minced muscle tissue, and rats exposed to 2H2O or 13C-enriched substrates. Myotubes or minced skeletal muscle incubated with [U-13C3]lactate released small amounts of [1,2,3-13C3]- or [4,5,6-13C3]glucose. This labeling pattern is consistent with direct transfer from lactate to glucose without randomization in the tricarboxylic acid (TCA) cycle. After exposure of incubated muscle to 2H2O, [U-13C3]lactate, glucose, and glutamine, there was minimal release of synthesized glucose to the medium based on a low level of 2H enrichment in medium glucose but 50- to 100-fold greater 2H enrichment in glucosyl units from glycogen. The 13C enrichment pattern in glycogen from incubated skeletal muscle was consistent only with direct transfer of lactate to glucose without exchange in TCA cycle intermediates. 13C nuclear magnetic resonance (NMR) spectra of glutamate from the same tissue showed flux from lactate through pyruvate dehydrogenase but not flux through pyruvate carboxylase into the TCA cycle. Carbon from an alternative substrate for glucose production that requires metabolism through the TCA cycle, propionate, did not enter glycogen, suggesting that TCA cycle intermediates do not exchange with phospho enolpyruvate. In vivo, the 13C labeling patterns in hepatic glycogen and plasma glucose after administration of [U-13C3]lactate did not differ significantly. However, skeletal muscle glycogen was substantially enriched in [1,2,3-13C3]- and [4,5,6-13C3]glucose units that could only occur through skeletal muscle glyconeogenesis rather than glycogenesis. Lactate serves as a substrate for glyconeogenesis in vivo without exchange into symmetric intermediates of the TCA cycle.

scholarly journals Tricarboxylic Acid (TCA) Cycle Intermediates: Regulators of Immune Responses

2020 ◽  
Author(s):  
Inseok Choi ◽  
Hyewon Son ◽  
Jea-Hyun Baek
Keyword(s):  
Immune Responses ◽  
Molecular Mechanisms ◽  
Tricarboxylic Acid Cycle ◽  
Tca Cycle ◽  
Tricarboxylic Acid ◽  
Cell Stress ◽  
Danger Signals ◽  
Cellular Processes ◽  
The Tca Cycle ◽  
Tca Cycle Intermediates

Tricarboxylic acid cycle (TCA) is a series of chemical reactions in aerobic organisms used to generate energy via the oxidation of acetyl-CoA derived from carbohydrates, fatty acids, and proteins. In the eukaryotic system, the TCA cycle completely occurs in mitochondria, while the intermediates of the TCA cycle are retained in mitochondria due to their polarity and hydrophilicity. Under conditions of cell stress, mitochondria become disrupted and release their contents, which act as danger signals in the cytosol. Of note, the TCA cycle intermediates may also leak from dysfunctioning mitochondria and regulate cellular processes. Increasing evidence shows that the metabolites of the TCA cycle are substantially involved in the regulation of immune responses. In this review, we aimed to provide a comprehensive systematic overview of the molecular mechanisms of each TCA cycle intermediate that may play key roles in regulating cellular immunity in cell stress and discuss their implications for immune activation and suppression.

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