Ketone-Body Concentrations in Liver and Blood after Limb Ischaemia in the Rat

1971 ◽  
Vol 40 (6) ◽  
pp. 463-477 ◽  
Author(s):  
R. N. Barton
Keyword(s):  
Fatty Acids ◽  
Hind Limb ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Regression Line ◽  
Early Response ◽  
Limb Ischaemia ◽  
Esterified Fatty Acids ◽  
Control Post ◽  
Body Concentration

1. The effect of a 4 h period of bilateral hind limb ischaemia on the concentrations of ketone bodies in blood and liver of post-absorptive and starved rats has been investigated. 2. The concentration of total ketone bodies in the blood did not change after injury in post-absorptive rats, but fell after injury in starved rats; the blood β-hydroxybutyrate/acetoacetate ratio fell after injury in both post-absorptive and starved rats. 3. Apart from a transient increase in fed rats, the hepatic β-hydroxybutyrate/acetoacetate ratio did not change after injury in post-absorptive or starved rats until the terminal stages, indicating adequate hepatic oxygenation during the early response to injury. 4. In control post-absorptive and starved rats the concentration of liver total ketone bodies was correlated with that of plasma non-esterified fatty acids; in post-absorptive rats the liver ketone body concentration rose after injury and was higher than would be predicted from the regression line for these controls, suggesting increased ketogenesis compatible with inhibition of complete oxidation of non-esterified fatty acids after injury. In contrast, in starved rats the liver total ketone-body concentration did not change after injury.

scholarly journals The metabolism of circulating non-esterified fatty acids by the whole animal, hind-limb muscle and uterus of pregnant ewes

1983 ◽  
Vol 49 (1) ◽  
pp. 129-143 ◽  
Author(s):  
D. W. Pethick ◽  
D. B. Lindsay ◽  
P. J. Barker ◽  
A. J. Northrop
Keyword(s):  
Fatty Acids ◽  
Hind Limb ◽  
Ketone Bodies ◽  
Gravid Uterus ◽  
Limb Muscle ◽  
Entry Rate ◽  
Esterified Fatty Acids ◽  
Arterial Concentration ◽  
Pregnant Sheep ◽  
Hind Limb Muscle

1. The over-all and regional metabolism of non-esterified fatty acids (NEFA) was studied using a combination of isotopic and arteriovenous-difference techniques.2. There was a common linear relationship, whether stearic, palmitic or oleic acids were used as tracer, between the arterial NEFA concentration and the rates of entry and oxidation.3. Assuming that the tracer used reflected the metabolism of all the NEFA, the total entry rate in fed and fasted pregnant ewes was (mean±SE) 0·44±0·02 and 0·55±0·07 mmol/h per kg body-weight respectively. Oxidation of NEFA contributed (mean±SE) 34±5 and 58±7% to the respiratory carbon dioxide in fed and fasted animals, this accounting for (mean±SE) 46±6 and 59±3% of the respective entry rates.4. Hind-limb muscle both utilized and produced NEFA. The mean gross fractional extraction (calculated from isotopic uptake) was (mean±SE) 9±1%. Gross utilization of any NEFA and appearance of 14CO2 across the muscle were linearly related to the arterial concentration of tracer fatty acid, irrespective of whether this was oleate or stearate. The amount of 14CO2 appearing was consistent with (mean±SE) 54±8% of the CO2 produced by the hind-limb being derived from NEFA oxidation.5. Infused NEFA were partly converted to ketone bodies. Uptake and oxidation in the hind-limb of ketones formed in the liver could account for approximately 20% of the 14CO2 apparently produced in muscle from NEFA. Correction for this reduces the proportion of CO2 derived from NEFA to 43%. There was some indication that ketones were also produced from NEFA in the hind-limb.6. NEFA were not a significant energy source for the gravid uterus.7. An over-all view of energy sources for the whole animal and for hind-limb muscle in normal and fasted pregnant sheep was presented.

scholarly journals Activities of enzymes of fat and ketone-body metabolism and effects of starvation on blood concentrations of glucose and fat fuels in teleost and elasmobranch fish

1979 ◽  
Vol 184 (2) ◽  
pp. 313-322 ◽  
Author(s):  
Victor A. Zammit ◽  
Eric A. Newsholme
Keyword(s):  
Fatty Acids ◽  
Ketone Body ◽  
Phosphoenolpyruvate Carboxykinase ◽  
Ketone Bodies ◽  
Carnitine Palmitoyltransferase ◽  
Blood Metabolites ◽  
Activity Data ◽  
Blood Concentrations ◽  
Esterified Fatty Acids ◽  
Coa Transferase

1. Activities of 3-oxo acid CoA-transferase and carnitine palmitoyltransferase together with tri- and di-acylglycerol lipase were present in red and heart muscles of the teleost fish. However, d-3-hydroxybutyrate dehydrogenase activity was not detectable. These results suggest that the heart and red muscles of the teleosts should be able to utilize the fat fuels triacylglycerol, fatty acids or acetoacetate, but not hydroxybutyrate. The muscles from the elasmobranchs differed in that d-3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities were present, but carnitine palmitoyltransferase activity was not detectable. This suggests that ketone bodies are the most important fat fuels in elasmobranchs. 2. The concentrations of acetoacetate, 3-hydroxybutyrate, glycerol, non-esterified fatty acids and triacylglycerols were measured in blood or plasma of several species of fish (teleosts and elasmobranchs) in the fed state. Teleosts have a 10-fold higher concentration of plasma non-esterified fatty acids, but a lower blood concentration of ketone bodies; both acetoacetate and 3-hydroxybutyrate are present in blood of elasmobranchs, whereas 3-hydroxybutyrate is absent from that of the teleosts. 3. The effects of starvation (up to 150 days) on the concentrations of blood metabolites were studied in a teleost (bass) and an elasmobranch (dogfish). In the bass there was a 60% decrease in blood glucose after 100 and 150 days starvation. In dogfish there was a large increase in the concentration of ketone bodies, whereas in bass the concentration of acetoacetate (the only ketone body present) remained low (<0.04mm) throughout the period of starvation. The concentration of plasma non-esterified fatty acids increased in bass, but decreased in dogfish. These changes are consistent with the predictions based on the enzyme-activity data. 4. Starvation did not change the activities of ketone-body-utilizing enzymes or that of phosphoenolpyruvate carboxykinase in heart and red skeletal muscles of both fish, but it decreased markedly the activity of phosphoenolpyruvate carboxykinase in white skeletal muscle of both fish. However, in the liver of the dogfish, starvation resulted in a twofold increase in the activities of 3-hydroxybutyrate dehydrogenase and acetoacetyl-CoA thiolase, whereas in bass liver it decreased the activity of acetoacetyl-CoA thiolase and increased that of 3-oxo acid CoA-transferase. The activity of phosphoenolpyruvate carboxykinase was increased twofold in the liver of bass, but was unchanged in that of the dogfish. 5. The difference in changes in concentrations of blood metabolites and enzyme activities in the two fish support the suggestion that, in starvation, ketone bodies, but not non-esterified fatty acids, are an important fuel for muscle in elasmobranchs, whereas non-esterified fatty acids, but not ketone bodies, are an important fuel in teleosts. The results are discussed in relation to the evolution of a discrete lipid-storing adipose tissue in teleosts and higher vertebrates.

Platelet-activating factor causes hypoketonaemia in starved rats

1992 ◽  
Vol 83 (4) ◽  
pp. 495-501
Author(s):  
Atsushi Hiraide ◽  
Rhys D. Evans ◽  
Dermot H. Williamson
Keyword(s):  
Fatty Acids ◽  
Blood Flow ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Acid Concentration ◽  
Intraperitoneal Injection ◽  
Ketone Body ◽  
Platelet Activating Factor ◽  
Esterified Fatty Acids ◽  
Body Concentration

1. The aim of this work was to examine whether platelet-activating factor could mimic the hypoketonaemia seen in septic and endotoxic experimental animals. Platelet-activating factor was administered either by the intraperitoneal (high dose) or intravenous (jugular vein, low dose) routes. 2. Intraperitoneal injection of platelet-activating factor (25 μg/kg body weight) decreased the blood ketone body concentration (acetoacetate plus 3-hydroxybutyrate) transiently (30 min after injection) in starved rats. Continuous intravenous infusion of platelet-activating factor (40 ng min−1 kg−1 for 5 h) caused comparable hypoketonaemia. 3. The hepatic acetoacetate concentration also decreased transiently after injection of platelet-activating factor and there was an increase in the 3-hydroxybutyrate/acetoacetate ratio. The hepatic ATP concentration decreased at 15 and 30 min after injection of platelet-activating factor. Infusion of platelet-activating factor caused a similar decrease in hepatic ketone body concentration, but no significant change in the 3-hydroxybutyrate/acetoacetate ratio or adenine nucleotide concentrations. 4. Platelet-activating factor administered by infusion, but not by injection, decreased the plasma non-esterified fatty acid concentration. The plasma glycerol concentration also decreased after infusion of platelet-activating factor, suggesting decreased lipolysis in adipose tissue. 5. Changes in plasma insulin concentration or white adipose tissue blood flow did not appear to contribute to the decrease in the plasma non-esterified fatty acid concentration after infusion of platelet-activating factor. However, there was a significant decrease in blood flow to interscapular brown adipose tissue in both the infused and injected groups. 6. These findings suggest that infusion of platelet-activating factor causes a decrease in ketone bodies by limiting the supply of non-esterified fatty acids to the liver, and that the transient hypoketonaemia seen with intraperitoneal injection may possibly be due to decreased oxidation of non-esterified fatty acids secondary to hepatic vasoconstriction.

scholarly journals Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

2016 ◽  
Vol 310 (2) ◽  
pp. E103-E115 ◽  
Author(s):  
Lionel Carneiro ◽  
Sarah Geller ◽  
Xavier Fioramonti ◽  
Audrey Hébert ◽  
Cendrine Repond ◽  
...  
Keyword(s):  
Food Intake ◽  
Ketone Body ◽  
Energy Homeostasis ◽  
Ketone Bodies ◽  
Glucose Production ◽  
Body Level ◽  
Homeostasis Regulation ◽  
The Impact ◽  
Body Concentration

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis.

scholarly journals Fatty acid metabolism in the perfused rat liver

1970 ◽  
Vol 119 (3) ◽  
pp. 525-533 ◽  
Author(s):  
H. A. Krebs ◽  
R. Hems
Keyword(s):  
Fatty Acids ◽  
Rat Liver ◽  
Ketone Body ◽  
Unsaturated Fatty Acids ◽  
Ketone Bodies ◽  
Saturated Fatty Acids ◽  
Perfused Rat Liver ◽  
Body Formation ◽  
Body Production ◽  
Chain Fatty Acids

1. The formation of acetoacetate, β-hydroxybutyrate and glucose was measured in the isolated perfused rat liver after addition of fatty acids. 2. The rates of ketone-body formation from ten fatty acids were approximately equal and independent of chain length (90–132μmol/h per g), with the exception of pentanoate, which reacted at one-third of this rate. The [β-hydroxybutyrate]/[acetoacetate] ratio in the perfusion medium was increased by long-chain fatty acids. 3. Glucose was formed from all odd-numbered fatty acids tested. 4. The rate of ketone-body formation in the livers of rats kept on a high-fat diet was up to 50% higher than in the livers of rats starved for 48h. In the livers of fat-fed rats almost all the O2 consumed was accounted for by the formation of ketone bodies. 5. The ketone-body concentration in the blood of fat-fed rats rose to 4–5mm and the [β-hydroxybutyrate]/[acetoacetate] ratio rose to 11.5. 6. When the activity of the microsomal mixed-function oxidase system, which can bring about ω-oxidation of fatty acids, was induced by treatment of the rat with phenobarbitone, there was no change in the ketone-body production from fatty acids, nor was there a production of glucose from even-numbered fatty acids. The latter would be expected if ω-oxidation occurred. Thus ω-oxidation did not play a significant role in the metabolism of fatty acids. 7. Arachidonate was almost quantitatively converted into ketone bodies and yielded no glucose, demonstrating that gluconeogenesis from poly-unsaturated fatty acids with an even number of carbon atoms does not occur. 8. The rates of ketogenesis from unsaturated fatty acids (sorbate, undecylenate, crotonate, vinylacetate) were similar to those from the corresponding saturated fatty acids. 9. Addition of oleate together with shorter-chain fatty acids gave only a slightly higher rate of ketone-body formation than oleate alone. 10. Glucose, lactate, fructose, glycerol and other known antiketogenic substances strongly inhibited endogenous ketogenesis but had no effects on the rate of ketone-body formation in the presence of 2mm-oleate. Thus the concentrations of free fatty acids and of other oxidizable substances in the liver are key factors determining the rate of ketogenesis.

scholarly journals Relationship between plasma and muscle concentrations of ketone bodies and free fatty acids in fed, starved and alloxan-diabetic states

1973 ◽  
Vol 134 (2) ◽  
pp. 499-506 ◽  
Author(s):  
Oliver E. Owen ◽  
Helene Markus ◽  
Stuart Sarshik ◽  
Maria Mozzoli
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Free Fatty Acids ◽  
Plasma Glucose ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Water Concentration ◽  
Diabetic Rats ◽  
Muscle Membrane

1. Concentrations of ketone bodies, free fatty acids and chloride in fed, 24–120h-starved and alloxan-diabetic rats were determined in plasma and striated muscle. Plasma glucose concentrations were also measured in these groups of animals. 2. Intracellular metabolite concentrations were calculated by using chloride as an endogenous marker of extracellular space. 3. The mean intracellular ketone-body concentrations (±s.e.m.) were 0.17±0.02, 0.76±0.11 and 2.82±0.50μmol/ml of water in fed, 48h-starved and alloxan-diabetic rats, respectively. Mean (intracellular water concentration)/(plasma water concentration) ratios were 0.47, 0.30 and 0.32 in fed, 48h-starved and alloxan-diabetic rats respectively. The relationship between ketone-body concentrations in the plasma and intracellular compartments appeared to follow an asymptotic pattern. 4. Only intracellular 3-hydroxybutyrate concentrations rose during starvation whereas concentrations of both 3-hydroxybutyrate and acetoacetate were elevated in the alloxan-diabetic state. 5. During starvation plasma glucose concentrations were lowest at 48h, and increased with further starvation. 6. There was no significant difference in the muscle intracellular free fatty acid concentrations of fed, starved and alloxan-diabetic rats. Mean free fatty acid intramuscular concentrations (±s.e.m.) were 0.81±0.08, 0.98±0.21 and 0.91±0.10μmol/ml in fed, 48h-starved and alloxan-diabetic states. 7. The intracellular ketosis of starvation and the stability of free fatty acid intracellular concentrations suggests that neither muscle membrane permeability nor concentrations of free fatty acids per se are major factors in limiting ketone-body oxidation in these states.

scholarly journals Young women partition fatty acids towards ketone body production rather than VLDL-TAG synthesis, compared with young men

2011 ◽  
Vol 105 (6) ◽  
pp. 857-865 ◽  
Author(s):  
Kyriakoula Marinou ◽  
Martin Adiels ◽  
Leanne Hodson ◽  
Keith N. Frayn ◽  
Fredrik Karpe ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Young Women ◽  
Metabolic Profile ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Young Men ◽  
Isotopic Enrichment ◽  
Plasma Nefa ◽  
Lower Plasma Glucose ◽  
Body Production

Before the menopause, women are relatively protected against CVD compared with men. The reasons for this sex difference are not completely understood, but hepatic fatty acid metabolism may play a role. The present study aimed to investigate the utilisation of plasma NEFA by the liver and to determine whether they are partitioned differently into ketone bodies and VLDL-TAG in healthy, lean young men and women. Volunteers were studied during a prolonged overnight fast (12–19 h) using an intravenous infusion of [U-13C]palmitate. After 12 h fasting, the women had a more advantageous metabolic profile with lower plasma glucose (P < 0·05) and TAG (P < 0·05) but higher plasma NEFA (P < 0·05) concentrations. Plasma 3-hydroxybutyrate (3-OHB) concentrations rose more in women than in men, and the transfer of13C from [U-13C]palmitate to plasma [13C]3-OHB reached a plateau 6–7 h after the start of the infusion in women but was still increasing at 6 h in men. This implies a slower 3-OHB production rate and/or dilution by other precursor pools in men. In women, the high isotopic enrichment of plasma 3-OHB suggested that systemic plasma fatty acids were the major source of 3-OHB production. However, in men, this was not observed during the course of the study (P < 0·01). There were no sex differences for the incorporation of13C into VLDL1- or VLDL2-TAG. The ability of young women to partition fatty acids towards ketone body production rather than VLDL-TAG may contribute to their more advantageous metabolic profile compared with young men.

Exchange of Metabolites in the Leg of Exercising Juvenile Diabetic Subjects

1978 ◽  
Vol 55 (1) ◽  
pp. 73-80 ◽  
Author(s):  
J. Lyngsøe ◽  
J. P. Clausen ◽  
J. Trap-Jensen ◽  
L. Sestoft ◽  
O. Schaffalitzky de Muckadell ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Glucose Uptake ◽  
Ketone Bodies ◽  
Normal Subjects ◽  
Close Correlation ◽  
Juvenile Diabetes ◽  
Control Subjects ◽  
Arterial Blood ◽  
Esterified Fatty Acids ◽  
And Control

1. Exchange of metabolic substrates was studied across the leg at rest and during a bicycle exercise demanding 50% of the maximal oxygen uptake in seven patients with juvenile diabetes and six control subjects. The leg blood flow and the femoral arterial and venous substrate concentrations were measured in the fasting state and, in the diabetic subjects, 24 h after the last administration of insulin. 2. At rest a close correlation was seen in the control subjects between the leg glucose uptake and the arterial insulin concentration. The diabetic subjects, including three patients in whom it could be shown that the insulin concentrations were extremely low, had a resting glucose uptake in the same order of magnitude as the control subjects. The glucose uptake was inversely related to the arterial concentrations of non-esterified fatty acids in both groups. 3. During exercise the glucose uptake increased in both patients and control subjects, but the increase was not related to arterial concentrations of insulin or non-esterified fatty acids. 4. The release of lactate, pyruvate, alanine and glycerol from the leg was not different in diabetic and control subjects neither at rest nor during exercise. 5. The ketonaemia was increased in the diabetic subjects, but the uptake of total ketone bodies was not different in the two groups. No increase in the uptake of total ketone bodies in control and diabetic subjects was found during exercise. The leg uptake of acetoacetate was a function of the substrate load and tended to be higher in diabetic subjects during exercise, when no net uptake of β-hydroxybutyrate was found. 6. The above results suggest that the glucose uptake in human skeletal muscle at rest depends on the concentration of insulin and possibly also of non-esterified fatty acids in arterial blood. In contrast the glucose uptake during exercise is not related to the concentration of insulin or non-esterified fatty acids, which may explain why no differences in this aspect are seen between the leg metabolism of diabetic and normal subjects.

scholarly journals Turnover rates of ketone bodies in normal, starved and alloxan-diabetic rats

1968 ◽  
Vol 110 (4) ◽  
pp. 655-661 ◽  
Author(s):  
Margaret W. Bates ◽  
H. A. Krebs ◽  
D. H. Williamson
Keyword(s):  
Ketone Body ◽  
Alloxan Diabetes ◽  
Ketone Bodies ◽  
Diabetic Rats ◽  
Turnover Rates ◽  
Blood Concentrations ◽  
Order Of Magnitude ◽  
The Mean ◽  
Body Production ◽  
Body Concentration

1. Rates of appearance and disappearance of total ketone bodies were determined in normal, starved and alloxan-diabetic rats by measuring specific radioactivities and concentrations of blood acetoacetate and 3-hydroxybutyrate at different times after injection of 3-hydroxy[14C]butyrate. 2. The mean rates of appearance were 1·7, 4·2 and 10·9μmoles/min./100g. body wt. respectively for normal, starved and alloxan-diabetic rats. The rates of disappearance were of the same order of magnitude as the rates of appearance. 3. There was a direct correlation between the rates of appearance and disappearance and the blood concentrations of the ketone bodies. 4. The results indicate that in the rat increased ketone-body production is paralleled by increased ketone-body utilization and that the raised ketone-body concentration in the blood in starvation and alloxan-diabetes is due to a slight imbalance between the rates of production and utilization. 5. The findings are discussed in relation to the concept that ketone bodies can serve as fuels of respiration when the supply of carbohydrate is limited.

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