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.

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 Role of Omega-3 Polyunsaturated Fatty Acids in the Production of Prostaglandin E2and Nitric Oxide during Experimental Murine Paracoccidioidomycosis

2013 ◽  
Vol 2013 ◽  
pp. 1-6 ◽  
Author(s):  
S. C. Sargi ◽  
M. M. O. Dalalio ◽  
A. G. Moraes ◽  
J. E. L. Visentainer ◽  
D. R. Morais ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Polyunsaturated Fatty Acids ◽  
Peritoneal Macrophages ◽  
Omega 3 Fatty Acids ◽  
Omega 3 ◽  
Potential Health ◽  
Macrophage Activity ◽  
Experimental Paracoccidioidomycosis

There has recently been increased interest in the potential health effects of omega-3 polyunsaturated fatty acids on the immune system. Paracoccidioidomycosis is the most important endemic mycosis in Latin America. Macrophages have a fundamental role and act as first line of organism defense. The purpose of this study was to analyze the effect of n-3 fatty acids on the production of PGE2and NO by mice infected with Pb18 and fed a diet enriched with LNA for 8 weeks. To study the effect of omega-3 fatty acids on macrophage activity during experimental paracoccidioidomycosis, mice were infected with Pb18 and fed a diet supplemented with LNA. PGE2in the serum of animals was analyzed and NO in the supernatants of macrophages cultured and challengedin vitrowith Pb18 was measured. Omega-3 fatty acids seemed to decrease the production of PGE2in vivoin the infected group fed an LNA-supplemented diet during the 4th and 8th weeks of the experiment. At the same time, we observed an increase in synthesis of NO by peritoneal macrophages in this group. Omega-3 fatty acids thus appear to have an immunomodulatory effect in paracoccidioidomycosis.

2,5-anhydro-D-mannitol: a fructose analogue that increases food intake in rats

1988 ◽  
Vol 254 (1) ◽  
pp. R150-R153 ◽  
Author(s):  
M. G. Tordoff ◽  
R. Rafka ◽  
M. J. DiNovi ◽  
M. I. Friedman
Keyword(s):  
Fatty Acids ◽  
Food Intake ◽  
Free Fatty Acids ◽  
Plasma Glucose ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Substrate Analogues ◽  
Increase Food Intake ◽  
Related Increase

We examined the effects on food intake and plasma fuels of 2,5-anhydro-D-mannitol (2,5-AM; 2-deoxy-D-fructose), a fructose analogue that inhibits hepatocyte gluconeogenesis and glycogenolysis in vitro. 2,5-AM (50-800 mg/kg po) given to rats during the diurnal fast produced a dose-related increase in food intake during the 2 h after administration. A 200-mg/kg dose of 2,5-AM decreased plasma glucose, increased plasma ketone bodies, free fatty acids, and glycerol, and had no effect on triglycerides. Normal and diabetic rats given 2,5-AM (200 mg/kg ip) increased food intake to the same extent. These results suggest that, unlike other substrate analogues that increase food intake, 2,5-AM increases feeding by creating a metabolic state that resembles fasting.

scholarly journals Metabolism of glucose, glutamine, long-chain fatty acids and ketone bodies by murine macrophages

1986 ◽  
Vol 239 (1) ◽  
pp. 121-125 ◽  
Author(s):  
P Newsholme ◽  
R Curi ◽  
S Gordon ◽  
E A Newsholme
Keyword(s):  
Fatty Acids ◽  
Citrate Synthase ◽  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
Tricarboxylic Acid ◽  
The Body ◽  
Acid Cycle ◽  
Coa Transferase ◽  
Very High

Maximum activities of some key enzymes of metabolism were studied in elicited (inflammatory) macrophages of the mouse and lymph-node lymphocytes of the rat. The activity of hexokinase in the macrophage is very high, as high as that in any other major tissue of the body, and higher than that of phosphorylase or 6-phosphofructokinase, suggesting that glucose is a more important fuel than glycogen and that the pentose phosphate pathway is also important in these cells. The latter suggestion is supported by the high activities of both glucose-6-phosphate dehydrogenase and 6-phosphogluconate dehydrogenase. However, the rate of glucose utilization by ‘resting’ macrophages incubated in vitro is less than the 10% of the activity of 6-phosphofructokinase: this suggests that the rate of glycolysis is increased dramatically during phagocytosis or increased secretory activity. The macrophages possess higher activities of citrate synthase and oxoglutarate dehydrogenase than do lymphocytes, suggesting that the tricarboxylic acid cycle may be important in energy generation in these cells. The activity of 3-oxoacid CoA-transferase is higher in the macrophage, but that of 3-hydroxybutyrate dehydrogenase is very much lower than those in the lymphocytes. The activity of carnitine palmitoyltransferase is higher in macrophages, suggesting that fatty acids as well as acetoacetate could provide acetyl-CoA as substrate for the tricarboxylic acid cycle. No detectable rate of acetoacetate or 3-hydroxybutyrate utilization was observed during incubation of resting macrophages, but that of oleate was 1.0 nmol/h per mg of protein or about 2.2% of the activity of palmitoyltransferase. The activity of glutaminase is about 4-fold higher in macrophages than in lymphocytes, which suggests that the rate of glutamine utilization could be very high. The rate of utilization of glutamine by resting incubated macrophages was similar to that reported for rat lymphocytes, but was considerably lower than the activity of glutaminase.

scholarly journals The peroxisomal transporter ABCD3 plays a major role in dicarboxylic fatty acid metabolism

2021 ◽  
Author(s):  
Pablo Ranea-Robles ◽  
Hongjie Chen ◽  
Brandon Stauffer ◽  
Chunli Yu ◽  
Dipankar Bhattacharya ◽  
...  
Keyword(s):  
Fatty Acids ◽  
De Novo ◽  
Ketone Bodies ◽  
De Novo Lipogenesis ◽  
Lipid Homeostasis ◽  
Hepatic Cholesterol Synthesis ◽  
Specific Subset

Peroxisomes metabolize a specific subset of fatty acids, which include dicarboxylic fatty acids (DCAs) generated by ω-oxidation. Data obtained in vitro suggest that the peroxisomal transporter ABCD3 (also known as PMP70) mediates the transport of DCAs into the peroxisome, but in vivo evidence to support this role is lacking. In this study, we studied an Abcd3 KO mouse model generated by CRISPR-Cas9 technology using targeted and untargeted metabolomics, histology, immunoblotting, and stable isotope tracing technology. We show that ABCD3 functions in DCA metabolism and uncover a novel role for this peroxisomal transporter in lipid metabolic homeostasis. The Abcd3 KO mouse presents with lipodystrophy, increased circulating free fatty acids, decreased ketone bodies, enhanced hepatic cholesterol synthesis and decreased hepatic de novo lipogenesis. Moreover, our study suggests that DCAs are metabolized by mitochondrial β-oxidation when ABCD3 is not functional, reflecting the importance of the metabolic compartmentalization and communication between peroxisomes and mitochondria. In summary, this study provides data on the role of the peroxisomal transporter ABCD3 in hepatic lipid homeostasis and DCA metabolism, and the consequences of peroxisomal dysfunction for the liver.

Effect of postburn serum on in vitro respiration of normal myocardium

1963 ◽  
Vol 18 (4) ◽  
pp. 821-823 ◽  
Author(s):  
Arthur A. Spector
Keyword(s):  
Fatty Acids ◽  
Oxygen Consumption ◽  
Technical Assistance ◽  
Ventricular Myocardium ◽  
Left Ventricular ◽  
Left Ventricular Myocardium ◽  
Burn Shock ◽  
Cardiac Defect ◽  
Electrophoretic Patterns

An in vitro respiratory system using normal guinea pig left ventricular myocardium is described. QO2 values are given for this preparation incubated with representative substrates. A larger elevation in oxygen consumption is seen with linoleic acid as compared to other unesterified fatty acids tested. Serum obtained from dogs before and 15 min after flash burn was incubated with this heart slice system. No differences in oxygen uptake are noted between addition of control and postburn serum. No major serum enzymatic or chemical alterations are found at 15 min postburn. Plasma protein electrophoretic patterns remain unchanged at 15 and 40 min after injury. These results do not support the concept that the cardiac defect in early burn shock is caused by a circulating substance that either inhibits oxidation or uncouples oxidative phosphorylation by the myocardium. Note: (With the Technical Assistance of Ralph A. Abreo and Raburn Jackson) Submitted on November 15, 1962

Renal substrate utilization in normal and acidotic rats

1987 ◽  
Vol 253 (2) ◽  
pp. F351-F357 ◽  
Author(s):  
L. Goldstein
Keyword(s):  
Fatty Acids ◽  
Urinary Excretion ◽  
Free Fatty Acids ◽  
Whole Blood ◽  
Ketone Bodies ◽  
Lactate Concentration ◽  
Arterial Lactate ◽  
Blood Flows ◽  
Cortical Slices

Renal arteriovenous (A-V) concentration differences of the major potential respiratory substrates were measured in whole blood of control, NH4Cl-acidotic and diabetic ketoacidotic (DKA) rats. Net renal substrate extractions were calculated from A-V differences and renal blood flows. In fed control rats lactate accounted for 78% of the total substrate extracted. Small amounts (10-12%) of citrate and the ketone bodies 3-hydroxybutyrate and acetoacetate were also extracted. There was no significant extraction of either free fatty acids, glucose, glutamine, or pyruvate. In NH4Cl-acidotic rats lactate extraction was lower (40%) than in controls, but glutamine extraction increased (28%). The amount of extra glutamine extracted approximated the fall in lactate extraction. In DKA rats, ketone bodies accounted for the major portion of the extracted substrates (56%) but a significant part of the net extraction was due to urinary excretion of these compounds. Glutamine extraction represented 23% of the total. Lactate extraction was low (14%) in DKA rats, probably as a result of the low arterial lactate concentration. In vitro studies done on renal cortical slices suggest that each of the three major substrates extracted by the kidneys of normal, NH4Cl, and DKA rats could serve as major respiratory fuels.

Glycogen metabolism in dog inner medullary collecting ducts

1994 ◽  
Vol 266 (3) ◽  
pp. F375-F383
Author(s):  
L. Meury ◽  
J. Senecal ◽  
J. Noel ◽  
P. Vinay
Keyword(s):  
Alternative Energy ◽  
Energy Requirement ◽  
Glycogen Synthesis ◽  
Glycogen Metabolism ◽  
Atp Turnover ◽  
Exogenous Glucose ◽  
Short Period ◽  
Collecting Ducts ◽  
Glycogen Breakdown

The regulation of glycogen degradation and synthesis in canine inner medullary collecting ducts (IMCD) was investigated using IMCD tubules suspensions prepared from dog papilla. A small but significant amount of glycogen was found in dog IMCD. Under aerobic condition and especially when no exogenous substrate is available, glycogen breakdown can support IMCD glycolysis for a short period of time. Increasing concentration of exogenous glucose but not lactate was able to reduce and even to suppress (20 mM glucose) the glycogen breakdown. A net synthesis of glycogen was observed only when the endogenous glycogen pool was previously partially or totally depleted. Under anaerobic condition, glycogenolysis was stimulated. The addition of up to 20 mM glucose now reduced but never suppressed this process. Glycogen metabolism responded to variation in the cells energy needs, since the net glycogen breakdown was diminished and glycogen synthesis increased when the cellular ATP turnover was reduced. The reverse effects were observed when the ATP turnover was increased. At all times, glycogen metabolism correlated well with changes in tissue glucose 6-phosphate concentration. The energy requirement of IMCD cells and the availability of alternative energy sources (active mitochondria, exogenous glucose) are therefore capable of eliciting an integrated and appropriate response of glycogen phosphorylase and synthase in IMCD tubules in suspension studied in vitro.

The Respiratory Exchange of the Desert Locust (Schistocerca Gregaria) before, During and After Flight

1951 ◽  
Vol 28 (3) ◽  
pp. 344-357 ◽  
Author(s):  
AUGUST KROGH ◽  
TORKEL WEIS-FOGH
Keyword(s):  
Oxygen Consumption ◽  
Schistocerca Gregaria ◽  
Ketone Bodies ◽  
Relative Rate ◽  
Unexpected Result ◽  
Desert Locust ◽  
Average Value ◽  
Short Period ◽  
Before And After ◽  
Small Container

The respiratory exchange of mature males of the Desert Locust Schistocerca gregaria (Forskål) has been studied during tethered flight in a small container and compared with the exchange before and after flights of varying duration. All determinations were based on gas analyses, and so the CO2 output and the O2 uptake were determined simultaneously. The accuracy of the analytical procedure has been discussed and the determinations of the R.Q. before and during flight found to be valid. The figures of the oxygen consumption are reduced to N.T.P. 1. During rest at 27-30°C the oxygen consumption amounted to 0.63 l. O2/kg./hr., which means that an average male of 1.8 g. consumed 18 cu.mm. O2 per min. During flight, however, the consumption increased fifteen to fifty times, the corresponding figures being 10-30 l. O2/kg./hr. or 300-900 cu.mm. O2 per min. in an average male. 2. After even a short period (10 min.) of flight in a roundabout or in front of a wind tunnel a distinct ‘oxygen debt’ was demonstrated. After prolonged flight (90-195 min.) the ‘debt’ was nearly doubled. It corresponded to 0.3-0.7 l. O2/kg. or to the oxygen consumption during only 0.5-1.5 min. of flight, so that anaerobic processes could not amount to much. It was characteristic that the recovery lasted at least 1 hr. 3. The R.Q. in resting animals averaged 0.82, and during the first 30 min. of flight the same value was obtained, but during the following 60 min. a statistically significant decrease of the R.Q. could be demonstrated, the average value in this period being 0.75. This unexpected result strongly indicates that, unlike other insects investigated so far, locusts utilize mainly fat as a source of energy during sustained flight. 4. It is suggested that a surplus of ketone bodies caused by the intensive breakdown of fats might explain the prolonged recovery of 1-2 hr. duration in Schistocerca, the recovery after flight in Drosophila which fly on carbohydrate lasting only 2 min. or less in spite of the same relative rate of combustion.

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