Blood Β-hydroxybutyrate Concentrations Research Articles

Chronic ketosis and cerebral metabolism.

The effects of chronic ketosis on cerebral metabolism were determined in adult rats maintained on a high-fat diet for approximately three weeks and compared to a control group of animals. The fat-fed rats had statistically significantly lower blood glucose concentrations and higher blood beta-hydroxybutyrate and acetoacetate concentrations; higher brain concentrations of bound glucose, glucose 6-phosphate, pyruvate, lactate, beta-hydroxybutyrate, citrate, alpha-ketoglutarate, alanine, and adenosine triphosphate (ATP); lower brain concentrations of fructose 1,6-diphosphate, aspartate, adenosine diphosphate (ADP), creatine, cyclic nucleotides, succinyl coenzyme A (CoA), acid-insoluble CoA, and total CoA; and similar brain concentrations of glucose, malate, calculated oxaloacetate, glutamate, glutamine, adenosine monophosphate, phosphocreatine, reduced CoA, acetyl CoA, sodium, potassium, chloride, and water content. The metabolite data in the chronically ketotic rats demonstrate an increase in the cerebral energy reserve and energy charge. These data also suggest negative modification of the enzymes phosphofructokinase, pyruvic dehydrogenase, and alpha-ketoglutaric dehydrogenase; positive modification of glycogen synthase; and possible augmentation of the hexose transport system. There was no demonstrable difference in brain pH, water content, or electrolytes in the two groups of animals. We speculate that the increased brain ATP/ADP ratio is central to most, if not all, the observed metabolic perturbations and may account for the increased neuronal stability that accompanies chronic ketosis.

EVIDENCE OF A ROLE FOR GLUCAGON IN REGULATING GLUCOSE AND β-HYDROXYBUTYRATE METABOLISM IN SHEEP

To evaluate the effect of glucagon on glucose and β-hydroxybutyrate metabolism, glucagon deficiency was induced by infusion of somatostatin. Glucose production rate and glucose and β-hydroxybutyrate concentrations were determined before, during and after somatostatin infusion. In order to minimize changes in insulin concentrations during somatostatin infusion, insulin-treated alloxanized sheep were used. Lowered glucagon concentrations after somatostatin infusion were associated with reduced glucose production and decreased blood glucose and β-hydroxybutyrate concentrations. This suggests that glucagon participates in maintaining the basal rate of gluconeogenesis in sheep and can influence hepatic ketogenesis.

LABORATORY STUDIES IN PATIENTS WITH REYES SYNDROME

Fifteen patients with Reyes Syndrome were prospectively studied according to a protocol designed to describe the course of the illness biochemically. Therapy consisted of careful fluid, electrolyte, acid-base and respiratory management. All patients demonstrated an increase in blood FFA (m = 3.1 meq/L), blood lactate (m = 2.8 mM), blood β-hydroxybutyrate (m = 1.5mM) and a decrease in plasma triglycerides (m = 38 mg%). The magnitude of these changes in stages II or III did not differentiate between ultimate survivors and non-survivors. Hypoglycemia occurred in two patients and was easily corrected by the administration of 5% glucose. This metabolic pattern is compatible with the hypothesis that Reyes Syndrome is characterized by a deficiency of glucose oxidation. If this hypothesis is correct, then the other observed abnormal laboratory findings (eg. an increase in serum CPK, amylase, and OCT activities an elevation in blood NH3 concentration; abnormal EEG, ST and T wave changes on EKG) which are accepted features of the illness may reflect multiple organ system involvement by the same process. A decrease in blood β-hydroxybutyrate concentration, suggesting a failure of ketogenesis, occurred in 5/5 clinical stage IV patients who ultimately expired. Decreased glucose oxidation appears to play role in the pathogenesis of Reyes Syndrome.

Regulation of ketone body metabolism in skeletal muscle

ARTICLESRegulation of ketone body metabolism in skeletal muscleNB Ruderman, and MN GoodmanNB RudermanSearch for more papers by this author, and MN GoodmanSearch for more papers by this authorPublished Online:01 Jun 1973https://doi.org/10.1152/ajplegacy.1973.224.6.1391MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByIn vitro ketone‐supported mitochondrial respiration is minimal when other substrates are readily available in cardiac and skeletal muscle19 August 2020 | The Journal of Physiology, Vol. 598, No. 21Pimozide Alleviates Hyperglycemia in Diet-Induced Obesity by Inhibiting Skeletal Muscle Ketone OxidationCell Metabolism, Vol. 31, No. 5Invited review: Metabolic challenges and adaptation during different functional stages of the mammary gland in dairy cows: Perspectives for sustainable milk productionJournal of Dairy Science, Vol. 102, No. 4Elevation of blood β-hydroxybutyrate concentration affects glucose metabolism in dairy cows before and after parturitionJournal of Dairy Science, Vol. 100, No. 3Thermic Effect of Food, Macronutrient Oxidation Rate and Satiety of Medium-chain TriglycerideKorean Journal of Community Nutrition, Vol. 20, No. 6Effects of dietary medium-chain fatty acids on performance, carcass characteristics, and some serum parameters of broiler chickens15 October 2014 | British Poultry Science, Vol. 55, No. 5Long-term elevation of β-hydroxybutyrate in dairy cows through infusion: Effects on feed intake, milk production, and metabolismJournal of Dairy Science, Vol. 96, No. 5Effects of structured medium- and long-chain triacylglycerols in diets with various levels of fat on body fat accumulation in rats9 March 2007 | British Journal of Nutrition, Vol. 91, No. 2Effects of a liquid diet supplement containing structured medium- and long-chain triacylglycerols on bodyfat accumulation in healthy young subjectsAsia Pacific Journal of Clinical Nutrition, Vol. 10, No. 1Unreliable use of standard muscle hydration value in obesityG. Mingrone, A. Bertuzzi, E. Capristo, A. V. Greco, M. Manco, A. Pietrobelli, S. Salinari, and S. B. Heymsfield1 February 2001 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 280, No. 2Malonyl-CoA, fuel sensing, and insulin resistanceNeil B. Ruderman, Asish K. Saha, Demetrios Vavvas, and Lee A. Witters1 January 1999 | American Journal of Physiology-Endocrinology and Metabolism, Vol. 276, No. 1Oxidation of d(?)3-hydroxybutyrate administered to rats with extensive burnsSurgery Today, Vol. 26, No. 3Uptake of β-hydroxybutyrate in perfused hindquarter of starved and diabetic ratsMetabolism, Vol. 40, No. 12Metabolism of ketone bodies by skeletal muscle in starvation and uncontrolled diabetesMetabolism, Vol. 39, No. 10Hepatic Ketogenesis and Peripheral Ketone Body Utilization in the RuminantThe Journal of Nutrition, Vol. 117, No. 6Ketone bodies inhibit leucine degradation in chick skeletal muscleInternational Journal of Biochemistry, Vol. 19, No. 10Ketone body kinetics in humans: the effects of insulin-dependent diabetes, obesity, and starvation.Journal of Lipid Research, Vol. 25, No. 11Effect of elevated substrates on substrate oxidation in normal and diabetic aortaActa Physiologica Scandinavica, Vol. 119, No. 4Metabolism of ketone bodies in pregnant sheep9 March 2007 | British Journal of Nutrition, Vol. 48, No. 3LIPID METABOLISM IN LIVER AND SELECTED TISSUES AND IN THE WHOLE BODY OF RUMINANT ANIMALSEnergy Metabolism in Feasting and FastingInfluence of Acetate on the Metabolism of β-Hydroxybutyrate in the Perfused Hind-Quarter of the RatActa Physiologica Scandinavica, Vol. 99, No. 1Metabolism of branched-chain amino acids in altered nutritionMetabolism, Vol. 25, No. 11Blood D-3-hydroxybutyrate and the regulation of plasma concentrations of free fatty acids in the fasted ratMetabolism, Vol. 25, No. 6Rhabdomyolysis And Myoglobinuria in ChildhoodPediatric Clinics of North America, Vol. 23, No. 2Effects of Long Lasting Physical Exercise and Training on Lipid MetabolismRenal conservation of ketone bodies during starvationMetabolism, Vol. 24, No. 1Transport of Organic Acids across Cell MembraneNew England Journal of Medicine, Vol. 291, No. 11Enzymes Involved in Ketone Utilization in Different Types of Muscle: Adaptation to ExerciseEuropean Journal of Biochemistry, Vol. 47, No. 3 More from this issue > Volume 224Issue 6June 1973Pages 1391-1397 Copyright & PermissionsCopyright © 1973 by American Physiological Societyhttps://doi.org/10.1152/ajplegacy.1973.224.6.1391PubMed4712152History Published online 1 June 1973 Published in print 1 June 1973 Metrics

Effect of cobalt chloride on the content of lipid and glycolytic intermediates in rabbit liver and heart.

The effects of cobalt chloride on various parameters of lipid and carbohydrate metabolism were examined in rabbit heart and liver. Hyperglycemia induced by cobalt chloride acted to elevate the glucose content of the heart, and also elevated the glucose, G-6-P and F-6-P content of the liver in starved rabbits.Marked elevation of plasma triglyceride levels in cobalt treated rabbits was accompanied by the accumulation of triglyceride in the liver; the triglyceride content of the heart was increased but not significantly, so. Cobalt acted to reduce the elevated concentration of plasma FFA induced by starvation. Plasma FFA might be utilized similarly in both cobalt-treated and starved rabbits to elevate the triglyceride content of the liver and the blood β-hydroxybutyrate concentration.

Contribution of Acetate, Butyrate, Palmitate, Stearate and Oleate to Ketone Body Synthesis in Sheep

[14C]-Labelled palmitate, oleate and stearate were each infused intravenously into sheep for between 4 and 6 hr. in separate experiments, and samples of blood were taken at frequent intervals to estimate the concentrations and specific radioactivities of the fatty acid and β-hydroxybutyrate. [14C] Acetate or [14C] butyrate was infused intraruminally and rumen and blood samples were taken for analysis. Comparison of the specific radioactivities of blood or rumen fatty acids with blood β-hydroxybutyrate during the terminal period of an infusion, indicated the extent of conversion of each fatty acid to β-hydroxybutyrate. Entry rates of β-hydroxy-butyrate were estimated, using [3H] β-hydroxybutyrate in some experiments, but in the majority of experiments a relationship between blood β-hydroxybutyrate concentration and entry rate based on previously reported results was used to predict the entry rate of β-hydroxy-butyrate. Between 78 and 94% of the β-hydroxybutyrate arose from rumen butyrate, with only small contributions from cither acetate or FFA. In animals starved for 1 day the contribution of butyrate to β-hydroxybutyrate synthesis was much lower, and after 2 to 4 days of starvation the contribution of FFA increased, apparently, to almost 100%. Only 15% of the butyrate produced in the rumen was converted to ketone bodies in sheep. It is suggested that in sheep which are feeding, most of the ketone bodies are produced from butyrate, and on the basis of the previous work, this probably occurs in the rumen epithelium. In animals starved for a number of days the ketone bodies are produced from FFA probably in the liver. The proportion of FFA converted to ketone bodies is not constant, but varies between I 33%.

Effect of carnitine on acidosis and ketosis induced by lipid perfusions in dogs during starvation

The effects of a single oral dose of carnitine on fasting-induced ketosis was investigated in four normal individuals, five patients with muscular dystrophy, and one patient with a generalized cytochrome c oxidase deficiency. Plasma carnitine, free fatty acids, glucose, insulin, and glucagon were also measured. Normal individuals showed an average 0.09 mm increase in blood β-hydroxybutyrate concentration during a 12- to 18-hr period of fasting and carnitine administration did not affect this response (average: 0.12 mm). Muscular dystrophy patients showed a greater fasting-induced elevation in β-hydroxybutyrate (average 0.29 mm) and carnitine administration greatly enhanced this ketogenic response (average 0.84 mm). The cytochrome c oxidase deficient patient showed an even larger increase in β-hydroxybutyrate with fasting (1.67 mm) and carnitine further augmented this ketotic effect (3.78 mm). Plasma free fatty acids were also elevated in patients that showed enhanced ketosis. Plasma glucagon concentration did not change, but insulin levels decreased during the 12- to 18-hr period of fasting; no major differences were found between controls and patients. These results indicate that some patients with muscular dystrophy and cytochrome c oxidase deficiency are more prone to develop ketosis than normal individuals and that carnitine administration enhances this response. Since both muscular dystrophy patients and the patient with cytochrome c oxidase deficiency had similar ketogenic responses, the data suggest that ketone body utilization may be impaired in these patients. The ability of l-carnitine to be ketogenic should be considered in the treatment of these patients.