scholarly journals Treatment with Nitrate, but Not Nitrite, Lowers the Oxygen Cost of Exercise and Decreases Glycolytic Intermediates While Increasing Fatty Acid Metabolites in Exercised Zebrafish

2019 ◽  
Vol 149 (12) ◽  
pp. 2120-2132 ◽  
Author(s):  
Elizabeth R Axton ◽  
Laura M Beaver ◽  
Lindsey St. Mary ◽  
Lisa Truong ◽  
Christiana R Logan ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Mitochondrial Function ◽  
Energy Production ◽  
Ketone Bodies ◽  
Oxygen Cost ◽  
Nitrate Treatment ◽  
Glycolytic Intermediates ◽  
Treated Fish ◽  
Nitrate And Nitrite

ABSTRACT Background Dietary nitrate improves exercise performance by reducing the oxygen cost of exercise, although the mechanisms responsible are not fully understood. Objectives We tested the hypothesis that nitrate and nitrite treatment would lower the oxygen cost of exercise by improving mitochondrial function and stimulating changes in the availability of metabolic fuels for energy production. Methods We treated 9-mo-old zebrafish with nitrate (sodium nitrate, 606.9 mg/L), nitrite (sodium nitrite, 19.5 mg/L), or control (no treatment) water for 21 d. We measured oxygen consumption during a 2-h, strenuous exercise test; assessed the respiration of skeletal muscle mitochondria; and performed untargeted metabolomics on treated fish, with and without exercise. Results Nitrate and nitrite treatment increased blood nitrate and nitrite levels. Nitrate treatment significantly lowered the oxygen cost of exercise, as compared with pretreatment values. In contrast, nitrite treatment significantly increased oxygen consumption with exercise. Nitrate and nitrite treatments did not change mitochondrial function measured ex vivo, but significantly increased the abundances of ATP, ADP, lactate, glycolytic intermediates (e.g., fructose 1,6-bisphosphate), tricarboxylic acid (TCA) cycle intermediates (e.g., succinate), and ketone bodies (e.g., β-hydroxybutyrate) by 1.8- to 3.8-fold, relative to controls. Exercise significantly depleted glycolytic and TCA intermediates in nitrate- and nitrite-treated fish, as compared with their rested counterparts, while exercise did not change, or increased, these metabolites in control fish. There was a significant net depletion of fatty acids, acyl carnitines, and ketone bodies in exercised, nitrite-treated fish (2- to 4-fold), while exercise increased net fatty acids and acyl carnitines in nitrate-treated fish (1.5- to 12-fold), relative to their treated and rested counterparts. Conclusions Nitrate and nitrite treatment increased the availability of metabolic fuels (ATP, glycolytic and TCA intermediates, lactate, and ketone bodies) in rested zebrafish. Nitrate treatment may improve exercise performance, in part, by stimulating the preferential use of fuels that require less oxygen for energy production.

scholarly journals Rates of utilization and fates of glucose, glutamine, pyruvate, fatty acids and ketone bodies by mouse macrophages

1987 ◽  
Vol 242 (3) ◽  
pp. 631-636 ◽  
Author(s):  
P Newsholme ◽  
S Gordon ◽  
E A Newsholme
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Ketone Bodies ◽  
Energy Requirement ◽  
Peritoneal Macrophages ◽  
Secretory Proteins ◽  
Short Period ◽  
Resting Lymphocytes ◽  
Almost All

The concentrations of ATP and the ATP/AMP concentration ratios were maintained in thioglycollate-elicited mouse peritoneal macrophages incubated in vitro for 90 min in the presence or absence of added substrate: rates of glycolysis, lactate formation and glutamine utilization were approximately linear with time for at least 60 min of incubation. The rate of oxygen consumption by macrophages was only increased above the basal rate (i.e. that in the absence of added substrate) by addition of succinate or pyruvate, or by addition of the uncoupling agent carboxyl cyanide m-chlorophenylhydrazone (‘CCCP’); it was decreased by 75% by the addition of KCN. These findings suggest that metabolism of endogenous substrate can provide most, if not all, of the energy requirement of these cells, at least for a short period. The rates of glucose and glutamine utilization by incubated macrophages were approx. 300 and 100 nmol/min per mg of protein respectively. A large proportion of the glutamine that is utilized is converted into glutamate and aspartate, and very little (perhaps less than 10%) is oxidized. Similarly almost all of the glucose that is utilized is converted into lactate and very little is oxidized. This characteristic is similar to that of resting lymphocytes and rapidly dividing cells; in non-proliferating macrophages it may be a mechanism to provide precision in control of the rate of biosynthetic processes that utilize intermediates of these pathways, e.g. purines and pyrimidines for mRNA for the synthesis of secretory proteins and glycerol 3-phosphate for phospholipid synthesis for membrane recycling. No utilization of acetoacetate or 3-hydroxybutyrate by macrophages was detected. In contrast, both butyrate and oleate were oxidized. The rate of [14C]oleate conversion into 14CO2 (1.3 nmol/h per mg of protein) could account for most of the oxygen consumption by incubated macrophages, suggesting that long-chain fatty acids might provide an important fuel in situ. This may be one explanation for the secretion of lipoprotein lipase by these cells, to provide fatty acids for oxidation from the degradation of local triacylglycerol.

Impact of altered substrate utilization on cardiac function in isolated hearts from Zucker diabetic fatty rats

2005 ◽  
Vol 288 (5) ◽  
pp. H2102-H2110 ◽  
Author(s):  
Peipei Wang ◽  
Steven G. Lloyd ◽  
Huadong Zeng ◽  
Arend Bonen ◽  
John C. Chatham
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Cardiac Function ◽  
Energy Production ◽  
Cardiac Metabolism ◽  
Low Flow ◽  
Control Group ◽  
Atp Production ◽  
Oxidation Rates ◽  
Zucker Diabetic Fatty Rats

The goal of this study was to determine whether changes in cardiac metabolism in Type 2 diabetes are associated with contractile dysfunction or impaired response to ischemia. Hearts from Zucker diabetic fatty (ZDF) and lean control rats were isolated and perfused with glucose, lactate, pyruvate, and palmitate. The rates of glucose, lactate, pyruvate, and palmitate oxidation rates and glycolysis were determined during baseline perfusion and low-flow ischemia (LFI; 0.3 ml/min for 30 min) and after LFI and reperfusion. Under all conditions, ATP synthesis from palmitate was increased and synthesis from lactate was decreased in the ZDF group, whereas the contribution from glucose was unchanged. During baseline perfusion, the rate of glycolysis was lower in the ZDF group; however, during LFI and reperfusion, there were no differences between groups. Despite these metabolic shifts, there were no differences in oxygen consumption or ATP production rates between the groups under any perfusion conditions. Cardiac function was slightly depressed before LFI in the ZDF group, but during reperfusion, function was improved relative to the control group despite the increased dependence on fatty acids for energy production. These data suggest that in this model of diabetes, the shift from carbohydrates to fatty acids for oxidative energy production did not increase myocardial oxygen consumption and was not associated with impaired response to ischemia and reperfusion.

Role of ketone bodies in perinatal myocardial energy metabolism

2001 ◽  
Vol 29 (2) ◽  
pp. 325-330 ◽  
Author(s):  
B. Bartelds ◽  
F. R. van der Leij ◽  
J. R. G. Kuipers
Keyword(s):  
Oxygen Consumption ◽  
Energy Production ◽  
Ketone Body ◽  
Myocardial Metabolism ◽  
Ketone Bodies ◽  
Left Ventricular ◽  
Energy Utilization ◽  
Long Chain Fatty Acids ◽  
Near Term

Metabolic changes at around the time of birth are crucial for life. Here we review the energy utilization in the myocardium, emphasizing ketone body metabolism. Before birth, glucose and lactate are the major energy substrates for the myocardium. Long-chain fatty acids (LCFA) are normally not available as an energy substrate for the fetal heart; however, when LCFA are supplied artificially in near-term fetal lambs, they are readily oxidized. Hence the myocardium has no limitation to its ability to use LCFA before birth. After birth, lactate remains an important energy source for the myocardium, whereas the contribution of glucose to myocardial energy production decreases despite an increase in the supply of glucose. The oxidation of ketone bodies increases after birth in relation to an increase in supply. However, ketone bodies account for only 7% of left ventricular oxygen consumption. The supply and contribution of LCFA to the myocardium increases after birth; the oxidation of LCFA accounts for most of the left ventricular oxygen consumption. Hence the role of ketone bodies in myocardial metabolism is limited. However, there are interesting observations on interference between the uptake of different substrates and the release of ketone bodies, which might have consequences for our interpretation of ketone body utilization.

The Vyredox and Nitredox Methods of in situ Treatment of Groundwater

1988 ◽  
Vol 20 (3) ◽  
pp. 149-163 ◽  
Author(s):  
Carol Braester ◽  
Rudolf Martinell
Keyword(s):  
Water Treatment ◽  
Surface Water ◽  
Traditional Method ◽  
Treatment Method ◽  
Nitrate Treatment ◽  
The Past ◽  
The World ◽  
Nitrate And Nitrite ◽  
Iron And Manganese

Nearly one fifth of all water used in the world is obtained from groundwater. The protection of water has become a high priority goal. During the last decades pollution of water has become more and more severe. Today groundwater is more and more used in comparison with surface water. Recently we have seen accidents, which can pollute nearly all surface water very quickly. Generally the groundwater is easier to protect, as well as cheaper to purify, and above all it is of better quality than the surface water. During the past two decades, alternatives to the traditional method of treating the water in filters have been developed, that is in situ water treatment i.e. the VYREDOX and NITREDOX methods. The most common problem regarding groundwater is too high content of iron and manganese, which can be reduced with the VYREDOX method. In some areas today there are severe problems with pollution by hydrocarbons and nitrate as well, and with modification of the VYREDOX treatment method it is used for hydrocarbon and nitrate treatment as well. The method to reduce the nitrate and nitrite is known as the NITREDOX method.

Effect of heparin-induced elevation of free fatty acids on myocardial oxygen consumption in man

1976 ◽  
Vol 37 (1) ◽  
pp. 167 ◽  
Author(s):  
William J. Rogers ◽  
Richard O. Russell ◽  
Roger E. Moraski ◽  
Huey G. McDaniel ◽  
Charles E. Rackley
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Free Fatty Acids ◽  
Myocardial Oxygen Consumption

Interconversion of pyruvate dehydrogenase in rat heart muscle upon perfusion with fatty acids or ketone bodies

FEBS Letters ◽  
1971 ◽  
Vol 15 (4) ◽  
pp. 295-298 ◽  
Author(s):  
O. Wieland ◽  
H.v. Funcke ◽  
G. Löffler
Keyword(s):  
Fatty Acids ◽  
Pyruvate Dehydrogenase ◽  
Heart Muscle ◽  
Rat Heart ◽  
Ketone Bodies

The energy requirement for sodium extrusion from a frog muscle

1954 ◽  
Vol 142 (908) ◽  
pp. 383-392 ◽  
Keyword(s):  
Oxygen Consumption ◽  
Energy Production ◽  
Energy Requirement ◽  
Metabolic Inhibitors ◽  
Sodium Efflux ◽  
External Potassium ◽  
Radioactive Sodium ◽  
Sodium Extrusion ◽  
Frog Sartorius ◽  
Made In

Parallel measurements have been made of the oxygen consumption and efflux of radioactive sodium in pairs of frog sartorius muscles. Calculation of the amount of secretory work necessary for an active extrusion of sodium at the observed rate showed that it would involve the utilization of about one-tenth of the energy available from resting metabolism.This figure may reasonably be regarded as a lower limit to the efficiency of the secretory mechanism. Some of the measurements were made in a potassium-free Ringer’s solution, and others with an external potassium concentration of 10mM. In the potassium-rich medium, both the sodium efflux and the oxygen consumption were increased, the proportion of the energy production required for sodium extrusion remaining roughly constant. The action of dinitrophenol and other metabolic inhibitors on the sodium efflux in sartorius muscles was examined, but there were no very obvious effects.

scholarly journals Effects of 3-hydroxybutyrate and free fatty acids on muscle protein kinetics and signaling during LPS-induced inflammation in humans: anticatabolic impact of ketone bodies

2018 ◽  
Vol 108 (4) ◽  
pp. 857-867 ◽  
Author(s):  
Henrik H Thomsen ◽  
Nikolaj Rittig ◽  
Mogens Johannsen ◽  
Andreas B Møller ◽  
Jens Otto Jørgensen ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Free Fatty Acids ◽  
Acute Inflammation ◽  
Ketone Bodies ◽  
Muscle Protein ◽  
Initiation Factor ◽  
Whole Body ◽  
Protein Breakdown ◽  
Protein Kinetics ◽  
Nonesterified Fatty Acids

Abstract Background Acute inflammation, and subsequent release of bacterial products (e.g. LPS), inflammatory cytokines, and stress hormones, is catabolic, and the loss of lean body mass predicts morbidity and mortality. Lipid intermediates may reduce protein loss, but the roles of free fatty acids (FFAs) and ketone bodies during acute inflammation are unclear. Objective We aimed to test whether infusions of 3-hydroxybutyrate (3OHB), FFAs, and saline reduce protein catabolism during exposure to LPS and Acipimox (to restrict and control endogenous lipolysis). Design A total of 10 healthy male subjects were randomly tested 3 times, with: 1) LPS, Acipimox (Olbetam) and saline, 2) LPS, Acipimox, and nonesterified fatty acids (Intralipid), and 3) LPS, Acipimox, and 3OHB, during a 5-h basal period and a 2-h hyperinsulinemic, euglycemic clamp. Labeled phenylalanine, tyrosine, and urea tracers were used to estimate protein kinetics, and muscle biopsies were taken for Western blot analysis of protein metabolic signaling. Results 3OHB infusion increased 3OHB concentrations (P < 0.0005) to 3.5 mM and decreased whole-body phenylalanine-to-tyrosine degradation. Basal and insulin-stimulated net forearm phenylalanine release decreased by >70% (P < 0.005), with both appearance and phenylalanine disappearance being profoundly decreased. Phosphorylation of eukaryotic initiation factor 2α at Ser51 was increased in skeletal muscle, and S6 kinase phosphorylation at Ser235/236 tended (P = 0.074) to be decreased with 3OHB infusion (suggesting inhibition of protein synthesis), whereas no detectable effects were seen on markers of protein breakdown. Lipid infusion did not affect phenylalanine kinetics, and insulin sensitivity was unaffected by interventions. Conclusion During acute inflammation, 3OHB has potent anticatabolic actions in muscle and at the whole-body level; in muscle, reduction of protein breakdown overrides inhibition of synthesis. This trial was registered at clinicaltrials.gov as NCT01752348.

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