scholarly journals Ketone-body utilization by adult and suckling rat brain in vivo

1971 ◽  
Vol 122 (1) ◽  
pp. 13-18 ◽  
Author(s):  
R. A. Hawkins ◽  
D. H. Williamson ◽  
H. A. Krebs
Keyword(s):  
Rat Brain ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Venous Blood ◽  
Adult Rats ◽  
Suckling Rats ◽  
Arterial Blood ◽  
The Brain ◽  
Body Concentration

1. Ketone-body utilization in fed and starved adult and suckling rats has been investigated by measuring arterio-venous differences across the brain. Venous blood was collected from the confluence of sinuses and arterial blood from the femoral artery in adult rats and by cardiac puncture in suckling rats. 2. During starvation the arterio-venous difference of ketone bodies increased in proportion to their concentrations in the blood and reached a value of 0.16mm at 48h. At a given concentration of the respective ketone bodies the arterio-venous differences of acetoacetate were about twice those of 3-hydroxybutyrate. 3. Fed rats in which the concentrations of ketone bodies were raised by intravenous infusion of sodium acetoacetate had the same arterio-venous differences as starved rats at corresponding ketone-body concentrations. Thus the ability of the rat brain to utilize ketone bodies is independent of the nutritional state. 4. The concentrations of glucose, acetoacetate and 3-hydroxybutyrate were much lower in the brain than in the arterial blood. The measured (blood concentration)/(brain concentration) ratio was 4.4 for glucose, 4.5 for acetoacetate and 8.1 for 3-hydroxybutyrate in 48h-starved rats. 5. The mean arterio-venous difference of glucose across the brain was 0.51mm in fed rats and 0.43mm in 96h-starved rats. 6. Conversion of glucose into lactate rose from negligible values in the fed state to 0.2mm after 48h starvation and decreased to zero after 96h starvation. 7. In 16–22-day-old suckling rats the arterio-venous differences of ketone bodies across the brain were also proportional to the ketone-body concentration, but they were about 3–4 times greater than in adult rats at the same blood ketone-body concentration. 8. Arterio-venous differences of glucose were about the same in adult and suckling rats. 9. The brain of fed suckling rats formed more lactate from glucose than fed adult rats. 10. The results indicate that ketone bodies are major metabolic fuels of the brain of the suckling rat under normal conditions.

scholarly journals Activities of enzymes of ketone-body utilization in brain and other tissues of suckling rats

1971 ◽  
Vol 121 (1) ◽  
pp. 49-53 ◽  
Author(s):  
M. Ann Page ◽  
H. A. Krebs ◽  
D. H. Williamson
Keyword(s):  
Rat Brain ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Rat Kidney ◽  
Adult Brain ◽  
Suckling Period ◽  
Suckling Rats ◽  
Adult Rat ◽  
Coa Transferase ◽  
High Concentrations

1. The activities of 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase in rat brain at birth were found to be about two-thirds of those of adult rat brain, expressed per g wet wt. The activities rose throughout the suckling period and at the time of weaning reached values about three times higher than those for adult brain. Later they gradually declined. 2. At birth the activity of acetoacetyl-CoA thiolase in rat brain was about 60% higher than in the adult. During the suckling period there was no significant change in activity. 3. In rat kidney the activities of the three enzymes at birth were less than one-third of those at maturity. They gradually rose and after 5 weeks approached the adult value. Similar results were obtained with rat heart. 4. The activity of glutamate dehydrogenase (a mitochondrial enzyme like 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase) also rose in brain and kidney during the suckling period, but at no stage did it exceed the adult value. 5. Throughout the suckling period the total ketone-body concentration in the blood was about six times higher than in adult fed rats, and the concentration of free fatty acids in the blood was three to four times higher. 6. It is concluded that the rate of ketone-body utilization in brains of suckling rats is determined by both the greater amounts of the key enzymes in the tissue and the high concentrations of ketone bodies in the blood. In addition, the low activities of the relevant enzymes in kidney and heart of suckling rats may make available more ketone bodies for the brain.

scholarly journals Activities of hexokinase, phosphofructokinase, 3-oxo acid coenzyme A-transferase and acetoacetyl-coenzyme A thiolase in nervous tissue from vertebrates and invertebrates

1973 ◽  
Vol 134 (1) ◽  
pp. 97-101 ◽  
Author(s):  
P. H. Sugden ◽  
E. A. Newsholme
Keyword(s):  
Nervous Tissue ◽  
Ketone Body ◽  
Glucose Utilization ◽  
Coenzyme A ◽  
Ketone Bodies ◽  
Animal Kingdom ◽  
Coa Transferase ◽  
Utilization Pathway ◽  
The Brain

1. The maximum activities of hexokinase and phosphofructokinase in nervous tissue from 18 different animals from different phyla range from 5.1 to 17.6 and from 24.0μmol/min per g fresh wt. respectively. In any one tissue the activities of these two enzymes are, in general, very similar. The rate of glucose utilization by the brain in vivo is much lower than the activities of hexokinase or phosphofructokinase. It is suggested that the high activities of these enzymes indicate a capacity for glycolysis which may be used by the brain during hypoxia or during conditions of extreme neuronal activity. 2. The activities of 3-oxo acid CoA-transferase and acetoacetyl-CoA thiolase in the nervous tissues range from 1.1 to 15.3 and from 0.7 to 4.5μmol/min per g fresh wt. respectively. Unfortunately the activities of these enzymes cannot be used to estimate maximal flux through the ketone-body-utilization pathway, since they may catalyse reactions that are close to equilibrium. Nonetheless, the presence of these enzymes in nervous tissue from a large variety of animals suggests that the importance of ketone bodies as a fuel for nervous tissue may be widespread in the animal kingdom.

scholarly journals Effect of phenylalanine metabolites on the activities of enzymes of ketone-body utilization in brain of suckling rats

1976 ◽  
Vol 160 (2) ◽  
pp. 217-222 ◽  
Author(s):  
J Benavides ◽  
C Gimenez ◽  
F Valdivieso ◽  
F Mayor
Keyword(s):  
Enzyme Activity ◽  
Mental Retardation ◽  
Rat Brain ◽  
Ketone Body ◽  
Lipid Synthesis ◽  
Developing Brain ◽  
Transferase Activity ◽  
Suckling Rats ◽  
Coa Transferase ◽  
The Brain

1. The effects of phenylalanine and its metabolites (phenylacetate, phenethylamine, phenyl-lactate, o-hydroxyphenylacetate and phenylpyruvate) on the activity of 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) 3-oxo acid CoA-transferase (EC 2.8.3.5) and acetoacetyl-CoA thiolase (EC 2.3.1.9) in brain of suckling rats were investigated. 2. The 3-hydroxybutyrate dehydrogenase from the brain of suckling rats had a Km for 3-hydroxybutyrate of 1.2 mM. Phenylpyruvate, phenylacetate and o-hydroxyphenylacetate inhibited the enzyme activity with Ki values of 0.5, 1.3 and 4.7 mM respectively. 3. The suckling-rat brain 3-oxo acid CoA-transferase activity had a Km for acetoacetate of 0.665 mM and for succinyl (3-carboxypropionyl)-CoA of 0.038 mM. The enzyme was inhibited with respect to acetoacetate by phenylpyruvate (Ki equals 1.3 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). The reaction in the direction of acetoacetate was also inhibited by phenylpyruvate (Ki equals 1.6 mM) and o-hydroxyphenylacetate (Ki equals 4.5 mM). 4. Phenylpyruvate inhibited with respect to acetoacetyl-CoA both the mitochondrial (Ki equals 3.2 mM) and cytoplasmic (Ki equals 5.2 mM) acetoacetyl-CoA thiolase activities. 5. The results suggest that inhibition of 3-hydroxybutyrate dehydrogenase and 3-oxo acid CoA-transferase activities may impair ketone-body utilization and hence lipid synthesis in the developing brain. This suggestion is discussed with reference to the pathogenesis of mental retardation in phenylketonuria.

Role of fat-derived substrates in the regulation of gluconeogenesis during fasting

1996 ◽  
Vol 270 (5) ◽  
pp. E822-E830 ◽  
Author(s):  
F. Fery ◽  
L. Plat ◽  
C. Melot ◽  
E. O. Balasse
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Glucose Turnover ◽  
Oxidation Rates ◽  
Relative Contribution ◽  
Beta Hydroxybutyrate ◽  
Hormonal Milieu ◽  
Body Concentration

To determine the role of fat-derived substrates in the regulation of glucose metabolism during fasting, glucose turnover, urea nitrogen production, alanine conversion to glucose, and substrate oxidation rates were measured in 34 normal 4-day-fasted volunteers treated with the antilipolytic drug acipimox or placebo for 8 h. The approximately 50% inhibition of lipolysis induced by acipimox increased glucose concentration and production, respectively, by approximately 35 and approximately 30%, whereas the protein breakdown and the amount of alanine converted to glucose were increased, respectively, by approximately 70 and approximately 85%. Insulin levels were reduced by approximately 40%, cortisol levels doubled, and growth hormone concentration increased sevenfold. The relative contribution of free fatty acid (FFA) and ketone body lowering to the observed response was evaluated in nine acipimox-treated subjects in whom ketone body concentration was clamped with an intravenous beta-hydroxybutyrate infusion. The results of these experiments suggest that, during fasting, both FFA and ketone bodies tend to suppress gluconceogenesis and to protect the protein stores. FFA seem to exert their effects mainly through their ability to modulate the hormonal milieu (especially insulin), whereas ketone bodies seem to act mainly by other mechanisms. Thus the widespread view according to which FFA exert a stimulatory role on gluconeogenesis does not apply to the fasting state in vivo.

scholarly journals Inhibition of sterol but not fatty acid synthesis by valproate in developing rat brain in vivo

1990 ◽  
Vol 272 (1) ◽  
pp. 251-253 ◽  
Author(s):  
J P Bolaños ◽  
J M Medina ◽  
D H Williamson
Keyword(s):  
Fatty Acid ◽  
Rat Brain ◽  
Fatty Acid Synthesis ◽  
Ketone Bodies ◽  
Acid Synthesis ◽  
Sterol Synthesis ◽  
Weanling Rats ◽  
Developing Rat ◽  
The Brain

The effect of administration of valproate on lipogenesis in the developing rat brain in vivo was studied. Valproate inhibited by 21-38% the rate of 3H2O incorporation into brain sterols, without significantly affecting fatty acid synthesis. Similarly, R-[2-14C]mevalonate incorporation into sterols was inhibited by 33-54%; the low rate of fatty acid synthesis under these conditions was not affected by valproate. Plasma ketone bodies decreased after treatment with valproate. Valproate inhibited (about 50%) both sterol and fatty acid synthesis in livers of weanling rats. It is concluded that valproate can specifically inhibit sterol synthesis in the brain during development, in part at a stage after mevalonate formation, and also by decreased exogenous precursor supply.

Metabolic Seizure Resistance via BAD and KATP Channels

2016 ◽  
Author(s):  
Juan Ramón Martínez-François ◽  
Nika N. Danial ◽  
Gary Yellen
Keyword(s):  
Glucose Metabolism ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Katp Channels ◽  
Anticonvulsant Effect ◽  
Metabolic Function ◽  
Genetic Ablation ◽  
Electrographic Seizures ◽  
The Brain

On a ketogenic diet, ketone bodies provide an alternative fuel, replacing much of the glucose used ordinarily by the brain. This switch is thought to underlie its anticonvulsant effects. Brain fuel utilization can also be modified by a nondietary approach: genetic alteration of the protein BAD, which has known roles in regulating both apoptosis and glucose metabolism. When the metabolic function of BAD is genetically altered in mice, it produces reduced glucose and increased ketone body metabolism in neurons and astrocytes. This effect is related to regulation of BAD by phosphorylation and is independent of its apoptotic function. Mice with BAD modifications that produce decreased glucose metabolism exhibit a marked increase in the activity of neuronal ATP-sensitive potassium (KATP) channels and strong resistance to behavioral and electrographic seizures in vivo. This seizure resistance is lost upon genetic ablation of KATP channels, suggesting that KATP channels mediate BAD’s anticonvulsant effect.

scholarly journals Incorporation of label from d-β-hydroxy-[14C]butyrate and [3-14C]acetoacetate into amino acids in rat brain in vivo

1971 ◽  
Vol 122 (2) ◽  
pp. 135-138 ◽  
Author(s):  
Jill E. Cremer
Keyword(s):  
Amino Acids ◽  
Rat Brain ◽  
Intravenous Injection ◽  
Ketone Bodies ◽  
Specific Radioactivity ◽  
Total Radioactivity ◽  
Soluble Material ◽  
The Brain

The metabolism of ketone bodies by rat brain was studied in vivo. Rats starved for 48h were given either d-β-hydroxy[3-14C]butyrate or [3-14C]acetoacetate by intravenous injection and killed after 3 or 10min. Total radioactivity in the acid-soluble material of the brain and the specific radioactivities of the brain amino acids glutamate, glutamine, aspartate and γ-aminobutyrate were determined. A group of fed animals were also given d-β-hydroxy[3-14C]butyrate. In the brains of all animals 14C was present in the acid-soluble material and the specific radioactivity of glutamate was greater than that of glutamine.

scholarly journals Supervised Machine Learning Methods and Hyperspectral Imaging Techniques Jointly Applied for Brain Cancer Classification

Sensors ◽  
2021 ◽  
Vol 21 (11) ◽  
pp. 3827
Author(s):  
Gemma Urbanos ◽  
Alberto Martín ◽  
Guillermo Vázquez ◽  
Marta Villanueva ◽  
Manuel Villa ◽  
...  
Keyword(s):  
Machine Learning ◽  
Blood Vessel ◽  
Hyperspectral Imaging ◽  
Imaging Techniques ◽  
Venous Blood ◽  
Healthy Tissue ◽  
Supervised Machine Learning ◽  
Support Vector ◽  
Arterial Blood

Hyperspectral imaging techniques (HSI) do not require contact with patients and are non-ionizing as well as non-invasive. As a consequence, they have been extensively applied in the medical field. HSI is being combined with machine learning (ML) processes to obtain models to assist in diagnosis. In particular, the combination of these techniques has proven to be a reliable aid in the differentiation of healthy and tumor tissue during brain tumor surgery. ML algorithms such as support vector machine (SVM), random forest (RF) and convolutional neural networks (CNN) are used to make predictions and provide in-vivo visualizations that may assist neurosurgeons in being more precise, hence reducing damages to healthy tissue. In this work, thirteen in-vivo hyperspectral images from twelve different patients with high-grade gliomas (grade III and IV) have been selected to train SVM, RF and CNN classifiers. Five different classes have been defined during the experiments: healthy tissue, tumor, venous blood vessel, arterial blood vessel and dura mater. Overall accuracy (OACC) results vary from 60% to 95% depending on the training conditions. Finally, as far as the contribution of each band to the OACC is concerned, the results obtained in this work are 3.81 times greater than those reported in the literature.

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.

In Vivo Analysis of Gas Transport in Arterial and Venous Blood of the Sea Lamprey Petromyzon Marinus

1992 ◽  
Vol 169 (1) ◽  
pp. 105-119
Author(s):  
B. L. TUFTS ◽  
B. BAGATTO ◽  
B. CAMERON
Keyword(s):  
Partial Pressure ◽  
Whole Blood ◽  
Venous Blood ◽  
Recovery Period ◽  
Co2 Concentration ◽  
Extracellular Acidosis ◽  
Arterial Blood ◽  
Sea Lampreys ◽  
In Vivo Analysis

Exercise in sea lampreys resulted in a significant decrease in the extracellular pH (pHe) in both arterial and venous blood. At rest, the erythrocyte pH (pHi) of venous blood was significantly greater than the pHi of arterial blood. Despite the considerable extracellular acidosis after exercise, both arterial and venous pHi were maintained throughout the recovery period. In the venous blood, there was a reversal of the pH gradient (ΔpH) across the erythrocyte membrane immediately after exercise. Exercise also resulted in significant reductions in the partial pressure of oxygen and hemoglobin oxygen-carriage and a significant increase in the partial pressure of CO2 in arterial and venous blood. Although the total CO2 concentration of the plasma decreased after exercise, erythrocyte total CO2 concentrations (CCOCO2,i) increased. In venous blood, the CCOCO2,i immediately after exercise was double the resting value. At rest, partitioning of the total CO2 content between plasma and erythrocytes indicated that 16 % and 22 % of the total CO2 could be attributed to the erythrocytes in arterial and venous whole blood, respectively. After exercise, these percentages increased to 25% (arterial) and 38% (venous). Changes in CCOCO2,i accounted for 62% of the arteriovenous difference in whole-blood total CO2 at rest. This increased to 78% immediately after exercise. Thus, unlike other vertebrates, CO2 transport in the lamprey in vivo is largely dependent on erythrocyte CO2-carriage.

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