scholarly journals Metabolism of ketone bodies in pregnant sheep

1982 ◽  
Vol 48 (3) ◽  
pp. 549-563 ◽  
Author(s):  
D. W. Pethick ◽  
D. B. Lindsay
Keyword(s):  
Skeletal Muscle ◽  
Hind Limb ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Maximum Velocity ◽  
Compartment Model ◽  
Entry Rate ◽  
Arterial Concentration ◽  
Pregnant Sheep ◽  
Ketone Body Metabolism

1. A combination of isotope-dilution and arteriovenous-difference techniques was used to determine the significance of ketones to energy homoeostasis in fasted pregnant ewes.2. There was incomplete interconversion of D(−) 3-hydroxybutyrate (3HB) and acetoacetate (AcAc) and therefore neither entry rate nor oxidation of total ketone bodies could be estimated by assuming circulating ketone bodies represent a single metabolic compartment. Total ketone body metabolism was satisfactorily summarized using a three-compartment model. In fasted pregnant ewes the mean entry rate of total ketones was 1 mmol/h per kg body-weight and of the ketones entering the circulation 87% were promptly oxidized to carbon dioxide accounting for 30% of the total COa production.3. Ketone bodies are readily utilized by hind-limb skeletal muscle such that if completely oxidized, 18±4 and 48±3% of the oxygen utilized could be accounted for in fed and fasted pregnant ewes respectively. For both 3HB and AcAc there was a hyperbolic relationship between utilization and arterial concentration. The apparent Michaelis constant (Km) values were 0·55 and 1–42 mM respectively and the maximum velocity (Vmax) 2·9 and 5·6 mmol/h per kg muscle. The arterial concentration of AcAc is always below the Km value and this limits the utilization rate. The D(−) 3HB concentration, however, may surpass that required for maximum utilization and ketoacidosis may be a consequence of this.4. A two-compartment model was used to analyse ketone body metabolism by hind-limb skeletal muscle. The results suggested substantial intercon version and production of AcAc and 3HB.5. The pregnant uterus utilized 3HB which if completely oxidized accounted for 12±2 (fed) and 25±4 (fasted) % of its O2 consumption. At least 64% of the net 3HB utilized was oxidized. AcAc was not utilized in significant quantities.

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 Non-esterified Long-chain Fatty Acid Metabolism in Fed Sheep at Rest and During Exercise

1987 ◽  
Vol 40 (2) ◽  
pp. 221 ◽  
Author(s):  
DW Pethick ◽  
N Harman ◽  
JK Chong
Keyword(s):  
Skeletal Muscle ◽  
Ketone Bodies ◽  
Long Chain Fatty Acids ◽  
Entry Rate ◽  
Long Chain Fatty Acid ◽  
Pregnant Sheep ◽  
Arteriovenous Difference ◽  
Long Chain ◽  
Sustained Increase

The role of circulating, non-esterified, long-chain fatty acids (NEFA) as a source of energy for the whole animal and skeletal muscle was investigated in fed non-pregnant sheep at rest and during exercise. Infusion of tracer quantities of [1-14C]oleic or [l-14C]stearic acid was combined with the use of arteriovenous difference studies on fed sheep at rest or during a 2 h period of exercise on a belt treadmill moving at 4� 5 km h -I. At rest all parameters of NEFA metabolism indicated a minimal role for oxidation. Thus the concentration in plasma (0'07 � 0�01 mmol I-I), entry rate (0'08 � 0�02 mmol h- I kg-I body wt), contribution to whole animal oxidation (1'2 � 0'3%) and utilization of NEFA by skeletal muscle (0'046 � 0�008 mmol h- I kg-I muscle) were all low. Exercise prompted a shift to lipolysis and accordingly the above parameters increased markedly some 13-24-fold. The circulating concentration of ketone bodies showed only a small increase during exercise and consequently the role of ketone bodies as an energy source during exercise was minimal. Glucose utilization by skeletal muscle was considerable in animals at rest and it represented the most significant potential fuel of skeletal muscle. Exercise resulted in a sustained increase of 3-4-fold in the utilization of glucose by skeletal muscle. Thus the traditional view that NEF A and not glucose is a predominant fuel of skeletal muscle of fed sheep should be appraised.

Ketone body metabolism in normal and diabetic human skeletal muscle

1985 ◽  
Vol 249 (2) ◽  
pp. E131-E136 ◽  
Author(s):  
R. Nosadini ◽  
A. Avogaro ◽  
L. Sacca ◽  
C. Vigorito ◽  
S. de Kreutzenberg ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Steady State ◽  
Human Skeletal Muscle ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Normal Subjects ◽  
Priming Dose ◽  
Tracer Concentration ◽  
Ketone Body Metabolism ◽  
Forearm Muscle

Although the liver is considered the major source of ketone bodies (KB) in humans, these compounds may also be formed by nonhepatic tissues. To study this aspect further, 3-[14C]hydroxybutyrate (BOH) or [3-14C]acetoacetate (AcAc) were constantly infused after a priming dose and contemporaneous arterial and venous samples were taken at splanchnic, heart, kidney, and leg sites in eight normal subjects (N) undergoing diagnostic catheterization and at the forearm site in five normal and six ketotic diabetic (D) subjects. After 70 min of infusion, tracer and tracee levels of AcAc and BOH reached a steady state in the artery and vein in both normal and diabetic subjects. The venous-arterial (V-A) difference at the forearm step for cold KB was negligible both in normal and diabetic subjects, whereas for labeled KB it was approximately 10-fold higher in diabetic subjects (V-A AcAc, -31 +/- 7 and -270 +/- 34 dpm/ml in N and D, respectively; V-A BOH, -38 +/- 6 and -344 +/- 126 dpm/ml in N and D, respectively). We assumed that the V-A difference in tracer concentration was consistent with dilution of the tracer by newly synthesized tracee inside the muscle and calculated that the forearm muscle produces KB at a rate of 16.2 +/- 3.3 mumol/min in D and 0.9 +/- 0.9 mumol/min in N. These findings can be accounted for by the hypothesis that the disappearance flux of KB from circulation was replaced by an equivalent flux of KB entering the vein at the muscle step in D but not in N. Moreover, in N KB were not only produced but also utilized by the splanchnic area (39 +/- 9 mumol/min).(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Hepatic ketone-body metabolism in developing sheep and pregnant ewes

1978 ◽  
Vol 40 (2) ◽  
pp. 359-367 ◽  
Author(s):  
G. Carole E. Varnam ◽  
Marjorie K. Jeacock ◽  
D. A. L. Shepherd
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Marked Change ◽  
Acetyl Coa ◽  
Adult Rats ◽  
Adult Sheep ◽  
Pregnant Sheep ◽  
Foetal Life ◽  
Ketone Body Metabolism

1. In order to establish whether or not there is a relationship between the blood ketone-body concentrations and the potential ability of the liver to synthesize ketone bodies in sheep on varying nutritional regimens, a study has been made of the concentrations of acetoacetate and 3-hydroxybutyrate in blood and the activities of enzymes concerned with ketogenesis in liver of developing sheep from mid-way through gestation to maturity, in pregnant ewes from mid-way through pregnancy and in starved pregnant and non-pregnant ewes.2. During development the most marked change in blood 3-hydroxybutyrate concentration occurred when the lambs were weaned. Blood acetoacetate concentrations did not change during development. When mature ewes were starved both 3-hydroxybutyrate and acetoacetate concentrations in blood were increased.3. Changes found in the activity of 3-hydroxybutyrate dehydrogenase (EC 1.1.1.30) in the liver were correlated with the changes in blood 3-hydroxybutyrate concentrations during development but no such relationship existed in pregnant or fasted ewes. No correlation was found between the ability of the liver to synthesize acetoacetate and blood ketone body concentrations in either developing or pregnant adult sheep. The rate of acetoacetate production expressed per g liver increased during foetal life but values observed in lambs 1 d after birth were similar to those found in suckling and mature sheep. During the last month of pregnancy and when non-pregnant sheep were starved the hepatic potential for ketogenesis was increased. During development the activity of acetyl-CoA acetyltransferase (EC 2.3.1.9) was correlated with the rate of hepatic acetoacetate production.4. These changes have been contrasted with those that occur in developing and starved adult rats.5. It is concluded that hepatic production of ketone bodies cannot be the only factor in the regulation of blood ketone body concentrations in developing and pregnant sheep.

scholarly journals Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats

1974 ◽  
Vol 138 (1) ◽  
pp. 1-10 ◽  
Author(s):  
Neil B. Ruderman ◽  
Peter S. Ross ◽  
Michael Berger ◽  
Michael N. Goodman
Keyword(s):  
Glucose Uptake ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Acetyl Coa ◽  
Total Blood ◽  
Diabetic Ketosis ◽  
Pyruvate Oxidation ◽  
Ketone Body Metabolism ◽  
Arteriovenous Difference ◽  
The Brain

1. The effects of starvation and diabetes on brain fuel metabolism were examined by measuring arteriovenous differences for glucose, lactate, acetoacetate and 3-hydroxybutyrate across the brains of anaesthetized fed, starved and diabetic rats. 2. In fed animals glucose represented the sole oxidative fuel of the brain. 3. After 48h of starvation, ketone-body concentrations were about 2mm and ketone-body uptake accounted for 25% of the calculated O2 consumption: the arteriovenous difference for glucose was not diminished, but lactate release was increased, suggesting inhibition of pyruvate oxidation. 4. In severe diabetic ketosis, induced by either streptozotocin or phlorrhizin (total blood ketone bodies >7mm), the uptake of ketone bodies was further increased and accounted for 45% of the brain 's oxidative metabolism, and the arteriovenous difference for glucose was decreased by one-third. The arteriovenous difference for lactate was increased significantly in the phlorrhizin-treated rats. 5. Infusion of 3-hydroxybutyrate into starved rats caused marked increases in the arteriovenous differences for lactate and both ketone bodies. 6. To study the mechanisms of these changes, steady-state concentrations of intermediates and co-factors of the glycolytic pathway were determined in freeze-blown brain. 7. Starved rats had increased concentrations of acetyl-CoA. 8. Rats with diabetic ketosis had increased concentrations of fructose 6-phosphate and decreased concentrations of fructose 1,6-diphosphate, indicating an inhibition of phosphofructokinase. 9. The concentrations of acetyl-CoA, glycogen and citrate, a potent inhibitor of phosphofructokinase, were increased in the streptozotocin-treated rats. 10. The data suggest that cerebral glucose uptake is decreased in diabetic ketoacidosis owing to inhibition of phosphofructokinase as a result of the increase in brain citrate. 11. The inhibition of brain pyruvate oxidation in starvation and diabetes can be related to the accelerated rate of ketone-body metabolism; however, we found no correlation between the decrease in glucose uptake in the diabetic state and the arteriovenous difference for ketone bodies. 12. The data also suggest that the rates of acetoacetate and 3-hydroxybutyrate utilization by brain are governed by their concentrations in plasma. 13. The finding of very low concentrations of acetoacetate and 3-hydroxybutyrate in brain compared with plasma suggests that diffusion across the blood –brain barrier may be the rate-limiting step in their metabolism.

scholarly journals Ketone body metabolism and cardiovascular disease

2013 ◽  
Vol 304 (8) ◽  
pp. H1060-H1076 ◽  
Author(s):  
David G. Cotter ◽  
Rebecca C. Schugar ◽  
Peter A. Crawford
Keyword(s):  
Cardiovascular Disease ◽  
Ketone Body ◽  
De Novo ◽  
Ketone Bodies ◽  
Tricarboxylic Acid Cycle ◽  
De Novo Lipogenesis ◽  
Short Supply ◽  
Nutritional Interventions ◽  
Diagnostic Strategies ◽  
Ketone Body Metabolism

Ketone bodies are metabolized through evolutionarily conserved pathways that support bioenergetic homeostasis, particularly in brain, heart, and skeletal muscle when carbohydrates are in short supply. The metabolism of ketone bodies interfaces with the tricarboxylic acid cycle, β-oxidation of fatty acids, de novo lipogenesis, sterol biosynthesis, glucose metabolism, the mitochondrial electron transport chain, hormonal signaling, intracellular signal transduction pathways, and the microbiome. Here we review the mechanisms through which ketone bodies are metabolized and how their signals are transmitted. We focus on the roles this metabolic pathway may play in cardiovascular disease states, the bioenergetic benefits of myocardial ketone body oxidation, and prospective interactions among ketone body metabolism, obesity, metabolic syndrome, and atherosclerosis. Ketone body metabolism is noninvasively quantifiable in humans and is responsive to nutritional interventions. Therefore, further investigation of this pathway in disease models and in humans may ultimately yield tailored diagnostic strategies and therapies for specific pathological states.

scholarly journals Ketone Body Metabolism in the Ischemic Heart

2021 ◽  
Vol 8 ◽  
Author(s):  
Stephen C. Kolwicz
Keyword(s):  
Ketone Body ◽  
Ketone Bodies ◽  
Ischemia Reperfusion ◽  
Ischemic Heart ◽  
Myocardial Infarctions ◽  
Ketogenic Diets ◽  
Health And Disease ◽  
Ketone Body Metabolism ◽  
Artery Disease ◽  
Fuel Source

Ketone bodies have been identified as an important, alternative fuel source in heart failure. In addition, the use of ketone bodies as a fuel source has been suggested to be a potential ergogenic aid for endurance exercise performance. These findings have certainly renewed interest in the use of ketogenic diets and exogenous supplementation in an effort to improve overall health and disease. However, given the prevalence of ischemic heart disease and myocardial infarctions, these strategies may not be ideal for individuals with coronary artery disease. Although research studies have clearly defined changes in fatty acid and glucose metabolism during ischemia and reperfusion, the role of ketone body metabolism in the ischemic and reperfused myocardium is less clear. This review will provide an overview of ketone body metabolism, including the induction of ketosis via physiological or nutritional strategies. In addition, the contribution of ketone body metabolism in healthy and diseased states, with a particular emphasis on ischemia-reperfusion (I-R) injury will be discussed.

KETONE BODY METABOLISM IN NUTRITIONAL MYOPATHY

1964 ◽  
Vol 42 (8) ◽  
pp. 1153-1160 ◽  
Author(s):  
K. J. Jenkins
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Oxidation ◽  
Ketone Body ◽  
Ketone Bodies ◽  
Pectoral Muscle ◽  
Acid Oxidation ◽  
Dystrophic Muscle ◽  
Liver Homogenates ◽  
Ketone Body Metabolism

A study was conducted on the metabolism of ketone bodies in tissue preparations from normal and dystrophic chicks. The data indicated that the production of ketone bodies in liver homogenates, as a result of fatty acid oxidation, was not markedly altered by development of the dystrophic condition. Whereas acetoacetate was oxidized by normal and degenerative pectoral muscle to approximately the same extent, utilization of β-hydroxybutyrate in dystrophic muscle was markedly poorer. In view of present concepts of the reactions involved in the metabolism of ketone bodies the results suggest that in the chick myopathy the conversion of β-hydroxybutyrate to acetoacetate may be impaired.

scholarly journals A high-MUFA diet alone does not affect ketone body metabolism, but reduces glycated hemoglobin when combined with exercise training in diabetic rats

2017 ◽  
Vol 9 (1) ◽  
pp. 31-40
Author(s):  
Juraiporn Somboonwong ◽  
Khunkhong Huchaiyaphum ◽  
Onanong Kulaputana ◽  
Phisit Prapunwattana
Keyword(s):  
Exercise Training ◽  
Ketone Body ◽  
Glycated Hemoglobin ◽  
Ketone Bodies ◽  
Transferase Activity ◽  
Nonesterified Fatty Acids ◽  
Regular Diet ◽  
Coa Transferase ◽  
Ketone Body Metabolism ◽  
Mufa Diet

Abstract Background Monounsaturated fat (MUFA) also has glucose-lowering action, but its effect on ketone bodies is unknown. Objectives To examine the effects of high-MUFA diet alone or in combination with exercise training, which can improve glucose and ketone body metabolism, in a rat model of diabetes. Methods Wistar rats were administered streptozotocin to induce diabetes and then randomly divided into five groups: sedentary rats fed a regular diet (1), a high-saturated-fat diet (2), a high-MUFA diet (3); and exercisetrained rats fed a regular diet (4), and a high-MUFA diet (5). Training was by a treadmill twice daily, 5 days/week. At 12 weeks, glucose, glycated hemoglobin (HbA1c), insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate levels were measured in cardiac blood. Activity of the overall ketone synthesis pathway was determined in liver and 3-ketoacyl-CoA transferase activity determined in gastrocnemius muscle. Results A high-MUFA diet tended to lower plasma glucose without affecting other biochemical variables. Training did not change glucose metabolism, but significantly reduced serum NEFA. Only the high-MUFA diet plus training significantly decreased HbA1c levels. Hepatic ketone synthesis was decreased and 3-ketoacyl-CoA transferase activity was increased by training alone or in combination with a high-MUFA diet. Changes in NEFA, β-hydroxybutyrate, and the enzymatic activities in response to training plus a high-MUFA diet were comparable to those caused by training alone. Conclusion A high-MUFA diet alone does not alter ketone body metabolism. Combination of a MUFA-rich diet and exercise training is more effective than either MUFA or exercise alone for lowering HbA1c.

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