ketone bodies

Summary

Summary: The substances beta-hydroxybutyric acid, acetoacetic acid, and acetone, which are produced by fatty acid and carbohydrate metabolism in the liver in approximately a 78:20:2 ratio. Acetoacetate is produced from acetyl-CoA. Most is enzymatically converted to beta-ketobutyrate, but a small amount is spontaneously decarboxylated to acetone. The ketone bodies can be used as fuels by muscle and brain tissue. In starvation and uncontrolled diabetes mellitus, large quantities are produced, causing metabolic acidosis and elevated blood and urine levels of all three ketone bodies. (Dorland, 28th ed)

Top Publications

  1. ncbi Ketone bodies, potential therapeutic uses
    R L Veech
    Unit on Metabolic Control, LMMB/NIAAA, Rockville, Maryland, USA
    IUBMB Life 51:241-7. 2001
  2. ncbi Cerebral ketone body metabolism
    A A M Morris
    Willink Biochemical Genetics Unit, Royal Manchester Children s Hospital, Hospital Road, Pendlebury, Manchester, M27 4HA, UK
    J Inherit Metab Dis 28:109-21. 2005
  3. pmc The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies
    Marwan Maalouf
    Department of Neurobiology, David Geffen School of Medicine, University of California, 63 323 CH5, Box 951763, Los Angeles, CA 90095 1763, USA
    Brain Res Rev 59:293-315. 2009
  4. ncbi Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes
    L Laffel
    Harvard Medical School, Joslin Clinic, One Joslin Place, Boston, MA 02215, USA
    Diabetes Metab Res Rev 15:412-26. 1999
  5. pmc Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy
    Gabriele D Maurer
    Dr Senckenberg Institute of Neurooncology, Goethe University Hospital, Schleusenweg 2 16, 60528 Frankfurt, Germany
    BMC Cancer 11:315. 2011
  6. pmc Ketone bodies and two-compartment tumor metabolism: stromal ketone production fuels mitochondrial biogenesis in epithelial cancer cells
    Ubaldo E Martinez-Outschoorn
    The Jefferson Stem Cell Biology and Regenerative Medicine Center, Department of Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA
    Cell Cycle 11:3956-63. 2012
  7. pmc Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells
    Ubaldo E Martinez-Outschoorn
    The Jefferson Stem Cell Biology and Regenerative Medicine Center, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
    Cancer Biol Ther 12:924-38. 2011
  8. doi Ketone bodies inhibit the viability of human neuroblastoma cells
    Robert Skinner
    Department of Surgery, University of Florida, Gainesville, 32608, USA
    J Pediatr Surg 44:212-6; discussion 216. 2009
  9. pmc Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet
    Shireesh Srivastava
    Laboratory of Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA
    FASEB J 26:2351-62. 2012
  10. ncbi Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes
    Amélie Pelletier
    Montreal Diabetes Research Centre, Centre Hospitalier de l Universite de Montreal, Montreal, Quebec, Canada
    Am J Physiol Endocrinol Metab 292:E1325-32. 2007

Detail Information

Publications224 found, 100 shown here

  1. ncbi Ketone bodies, potential therapeutic uses
    R L Veech
    Unit on Metabolic Control, LMMB/NIAAA, Rockville, Maryland, USA
    IUBMB Life 51:241-7. 2001
    ..This technical strategy will be critical to the characterization of polygenic disorders by enhancing the knowledge gained from gene analysis and from the subsequent steps and modifications of the protein products themselves...
  2. ncbi Cerebral ketone body metabolism
    A A M Morris
    Willink Biochemical Genetics Unit, Royal Manchester Children s Hospital, Hospital Road, Pendlebury, Manchester, M27 4HA, UK
    J Inherit Metab Dis 28:109-21. 2005
    b>Ketone bodies (KBs) are an important source of energy for the brain. During the neonatal period, they are also precursors for the synthesis of lipids (especially cholesterol) and amino acids...
  3. pmc The neuroprotective properties of calorie restriction, the ketogenic diet, and ketone bodies
    Marwan Maalouf
    Department of Neurobiology, David Geffen School of Medicine, University of California, 63 323 CH5, Box 951763, Los Angeles, CA 90095 1763, USA
    Brain Res Rev 59:293-315. 2009
    ..partially, the neuroprotective effects of the diets with less demanding changes to food intake suggests that ketone bodies might represent an appropriate candidate...
  4. ncbi Ketone bodies: a review of physiology, pathophysiology and application of monitoring to diabetes
    L Laffel
    Harvard Medical School, Joslin Clinic, One Joslin Place, Boston, MA 02215, USA
    Diabetes Metab Res Rev 15:412-26. 1999
    b>Ketone bodies are produced by the liver and used peripherally as an energy source when glucose is not readily available...
  5. pmc Differential utilization of ketone bodies by neurons and glioma cell lines: a rationale for ketogenic diet as experimental glioma therapy
    Gabriele D Maurer
    Dr Senckenberg Institute of Neurooncology, Goethe University Hospital, Schleusenweg 2 16, 60528 Frankfurt, Germany
    BMC Cancer 11:315. 2011
    ..Under these conditions, ketone bodies are generated serving as an important energy source at least for non-transformed cells.
  6. pmc Ketone bodies and two-compartment tumor metabolism: stromal ketone production fuels mitochondrial biogenesis in epithelial cancer cells
    Ubaldo E Martinez-Outschoorn
    The Jefferson Stem Cell Biology and Regenerative Medicine Center, Department of Stem Cell Biology and Regenerative Medicine, Thomas Jefferson University, Philadelphia, PA, USA
    Cell Cycle 11:3956-63. 2012
    ..In addition, treatment with ketone bodies (such as 3-hydroxy-butyrate, and/or butanediol) is sufficient to drive mitochondrial biogenesis in human ..
  7. pmc Anti-estrogen resistance in breast cancer is induced by the tumor microenvironment and can be overcome by inhibiting mitochondrial function in epithelial cancer cells
    Ubaldo E Martinez-Outschoorn
    The Jefferson Stem Cell Biology and Regenerative Medicine Center, Kimmel Cancer Center, Thomas Jefferson University, Philadelphia, PA, USA
    Cancer Biol Ther 12:924-38. 2011
    ..Treatment of MCF7 cells cultured alone with high-energy mitochondrial "fuels" (L-lactate or ketone bodies) is sufficient to confer tamoxifen resistance, mimicking the effects of coculture with fibroblasts...
  8. doi Ketone bodies inhibit the viability of human neuroblastoma cells
    Robert Skinner
    Department of Surgery, University of Florida, Gainesville, 32608, USA
    J Pediatr Surg 44:212-6; discussion 216. 2009
    ..tumor cells, unlike normal brain cells, are largely dependent upon glucose for energy and are not able to use ketone bodies as a primary energy source...
  9. pmc Mitochondrial biogenesis and increased uncoupling protein 1 in brown adipose tissue of mice fed a ketone ester diet
    Shireesh Srivastava
    Laboratory of Metabolic Control, National Institute on Alcohol Abuse and Alcoholism, National Institutes of Health, Rockville, Maryland 20852, USA
    FASEB J 26:2351-62. 2012
    ..The quantitative insulin-sensitivity check index was 73% higher in the KE group. These results identify KE as a potential antiobesity supplement...
  10. ncbi Ketone bodies alter dinitrophenol-induced glucose uptake through AMPK inhibition and oxidative stress generation in adult cardiomyocytes
    Amélie Pelletier
    Montreal Diabetes Research Centre, Centre Hospitalier de l Universite de Montreal, Montreal, Quebec, Canada
    Am J Physiol Endocrinol Metab 292:E1325-32. 2007
    ..Thus abnormal regulation of glucose uptake may contribute to the development of cardiac disease in diabetics. Ketone bodies are often elevated in poorly controlled diabetics and are associated with increased cellular oxidative stress...
  11. pmc Ketone bodies in epilepsy
    Melanie A McNally
    Johns Hopkins University School of Medicine, Baltimore, MD, USA
    J Neurochem 121:28-35. 2012
    ..The diet received its name based on the observation that patients consuming this diet produce ketone bodies (e.g., acetoacetate, β-hydroxybutyrate, and acetone)...
  12. pmc 2-Deoxy-D-glucose treatment induces ketogenesis, sustains mitochondrial function, and reduces pathology in female mouse model of Alzheimer's disease
    Jia Yao
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, United States of America
    PLoS ONE 6:e21788. 2011
    ..Collectively, these data provide preclinical evidence for dietary 2-DG as a disease-modifying intervention to delay progression of bioenergetic deficits in brain and associated β-amyloid burden...
  13. ncbi Ketone bodies stimulate chaperone-mediated autophagy
    Patrick F Finn
    Department of Molecular and Cellular Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111, USA
    J Biol Chem 280:25864-70. 2005
    ..b>Ketone bodies are comprised of three compounds (beta-hydroxybutyrate, acetoacetate, and acetone) that circulate during ..
  14. pmc Identification and characterization of an extramitochondrial human 3-hydroxy-3-methylglutaryl-CoA lyase
    Christa Montgomery
    Division of Molecular Biology and Biochemistry, University of Missouri, Kansas City, Missouri 64110, USA
    J Biol Chem 287:33227-36. 2012
    ..The available results for COS1 cell expression, as well as endogenous expression in U87 cells, indicate that HMGCLL1 is an extramitochondrial hydroxymethylglutaryl-CoA lyase...
  15. ncbi Breath acetone predicts plasma ketone bodies in children with epilepsy on a ketogenic diet
    Kathy Musa-Veloso
    Department of Nutritional Sciences, University of Toronto, Toronto, Ontario, Canada
    Nutrition 22:1-8. 2006
    ....
  16. ncbi The anticonvulsant activity of acetone, the major ketone body in the ketogenic diet, is not dependent on its metabolites acetol, 1,2-propanediol, methylglyoxal, or pyruvic acid
    Maciej Gasior
    Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 3702, USA
    Epilepsia 48:793-800. 2007
    Acetone, one of the principal ketone bodies elevated during treatment with the ketogenic diet, exhibits anticonvulsant properties that may contribute to the seizure protection conferred by the diet...
  17. ncbi Is there an astrocyte-neuron ketone body shuttle?
    M Guzman
    Dept Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain
    Trends Endocrinol Metab 12:169-73. 2001
    b>Ketone bodies can replace glucose as the major source of brain energy when glucose becomes scarce...
  18. doi Central infusion of ketone bodies modulates body weight and hepatic insulin sensitivity by modifying hypothalamic leptin and insulin signaling pathways in type 2 diabetic rats
    Sunmin Park
    Dept of Food and Nutrition, Obesity Diabetes Center, College of Natural Science, Hoseo University, Asan Si, Republic of Korea
    Brain Res 1401:95-103. 2011
    ..In conclusion, mild ketosis by central infusion of ketones improves energy and glucose metabolism through the potentiation of leptin and insulin signaling in the hypothalamus of diabetic rats...
  19. pmc Ketone bodies, glycolysis, and KATP channels in the mechanism of the ketogenic diet
    Gary Yellen
    Department of Neurobiology, Harvard Medical School, Boston, Massachusetts 02115, USA gary
    Epilepsia 49:80-2. 2008
    ..Several hypotheses focus on ketone bodies, fuel molecules that circulate at millimolar concentrations in the blood of patients on a KD, as causative ..
  20. ncbi Inhibition of fructose 1,6-bisphosphatase reduces excessive endogenous glucose production and attenuates hyperglycemia in Zucker diabetic fatty rats
    Paul D van Poelje
    Department of Biochemistry, Metabasis Therapeutics, 11119 North Torrey Pines Rd, La Jolla, CA 92037, USA
    Diabetes 55:1747-54. 2006
    ..The studies confirm that excessive gluconeogenesis plays an integral role in the pathophysiology of type 2 diabetes and suggest that FBPase inhibitors may provide a future treatment option...
  21. ncbi Anesthetic properties of the ketone bodies beta-hydroxybutyric acid and acetone
    Liya Yang
    Department of Anesthesia and Perioperative Care, University of California, San Francisco, California 94143 0464, USA
    Anesth Analg 105:673-9. 2007
    ..We tested the hypothesis that two metabolites that are elevated in ketosis (beta-hydroxybutyric acid, and acetone) modulate ion channels in a manner similar to anesthetics and produce anesthesia in animals...
  22. doi High-performance liquid chromatography determination of ketone bodies in human plasma by precolumn derivatization with p-nitrobenzene diazonium fluoroborate
    Susumu Yamato
    Department of Bioanalytical Chemistry, Faculty of Pharmaceutical Sciences, Niigata University of Pharmacy and Applied Life Sciences, Niigata, Niigata 956 8603, Japan
    Anal Biochem 384:145-50. 2009
    ..and convenient high-performance liquid chromatography (HPLC) method for the specific determination of ketone bodies (acetoacetate and D-3-hydroxybutyrate) in human plasma...
  23. ncbi Metabolic response to a ketogenic breakfast in the healthy elderly
    E Freemantle
    Research Center on Aging, Health, and Social Services Center, Sherbrooke University Geriatrics Institute, 1036 Belvédère S, Sherbrooke, QC, Canada
    J Nutr Health Aging 13:293-8. 2009
    ..To determine whether the metabolism of glucose or ketones differs in the healthy elderly compared to young or middle-aged adults during mild, short-term ketosis induced by a ketogenic breakfast...
  24. ncbi Enzyme activities support the use of liver lipid-derived ketone bodies as aerobic fuels in muscle tissues of active sharks
    R R Watson
    Department of Biological Science, California State University-Fullerton, Fullerton, CA 92834, USA
    Physiol Biochem Zool 74:273-82. 2001
    Few data exist to test the hypothesis that elasmobranchs utilize ketone bodies rather than fatty acids for aerobic metabolism in muscle, especially in continuously swimming, pelagic sharks, which are expected to be more reliant on lipid ..
  25. pmc Oxidative impairment of hippocampal long-term potentiation involves activation of protein phosphatase 2A and is prevented by ketone bodies
    Marwan Maalouf
    Division of Neurology, Cedars Sinai Medical Center, Los Angeles, California, USA
    J Neurosci Res 86:3322-30. 2008
    Previous studies have shown that ketone bodies (KB) exert antioxidant effects in experimental models of neurological disease...
  26. doi Simultaneous clinical monitoring of lactic acid, pyruvic acid and ketone bodies in plasma as methoxime/tert-butyldimethylsilyl derivatives by gas chromatography-mass spectrometry in selected ion monitoring mode
    Man Jeong Paik
    Metabolomic Analysis Laboratory, Institute for Neuroregeneration and Stem Cell Research, Ajou University, Wonchon dong, Yeongtong Gu, Suwon 443 721, South Korea
    Biomed Chromatogr 22:450-3. 2008
    ..2-7.6), with detection limits of 0.05-1.7 ng/mL. This rapid, accurate and selective method using minimal plasma samples (20 microL) is useful in the clinical monitoring of lactic acidosis and ketone body formation in plasma...
  27. pmc The depolarizing action of GABA in cultured hippocampal neurons is not due to the absence of ketone bodies
    Jaylyn Waddell
    Department of Physiology, University of Maryland School of Medicine, Baltimore, Maryland, United States of America
    PLoS ONE 6:e23020. 2011
    ..The authors argue that this does not mimic the physiological environment because the suckling rats use ketone bodies and pyruvate as major sources of metabolic energy...
  28. pmc Cerebral metabolic adaptation and ketone metabolism after brain injury
    Mayumi L Prins
    1UCLA Division of Neurosurgery, Los Angeles, California 90095, USA
    J Cereb Blood Flow Metab 28:1-16. 2008
    The developing central nervous system has the capacity to metabolize ketone bodies. It was once accepted that on weaning, the 'post-weaned/adult' brain was limited solely to glucose metabolism...
  29. doi The biochemistry of ketogenesis and its role in weight management, neurological disease and oxidative stress
    Peter Andrew C McPherson
    Belfast Metropolitan College, Titanic Quarter Campus, School of Applied Science Chemistry, Belfast, Northern Ireland BT3 9DT, UK
    J Physiol Biochem 68:141-51. 2012
    Ketogenesis is the branch of mammalian metabolism concerned with the synthesis of ketone bodies. In this process, the small, water-soluble compounds acetoacetate, D-3-β-hydroxybutyrate and propanone are produced by the liver in response ..
  30. pmc A monocarboxylate transporter required for hepatocyte secretion of ketone bodies during fasting
    Sarah E Hugo
    University of Utah Molecular Medicine U2M2 Program, Division of Endocrinology, Metabolism, and Diabetes, University of Utah, Salt Lake City, Utah 84112, USA
    Genes Dev 26:282-93. 2012
    ..Since β-hydroxybutyrate is both a major fuel and a signaling molecule in fasting, the discovery of this transporter provides a new direction for modulating circulating levels of ketone bodies in metabolic diseases.
  31. pmc A ketogenic diet as a potential novel therapeutic intervention in amyotrophic lateral sclerosis
    Zhong Zhao
    Neuroinflammation Research Laboratories, Department of Psychiatry, USA
    BMC Neurosci 7:29. 2006
    ..The cause of neuronal death in amyotrophic lateral sclerosis (ALS) is uncertain but mitochondrial dysfunction may play an important role. Ketones promote mitochondrial energy production and membrane stabilization...
  32. doi Chronic in vitro ketosis is neuroprotective but not anti-convulsant
    Marina Samoilova
    Division of Fundamental Neurobiology, Toronto Western Research Institute, Toronto, Ontario, Canada
    J Neurochem 113:826-35. 2010
    ..Yet, a direct role for ketone bodies in limiting seizure and neuronal damage remains poorly understood...
  33. ncbi Developmental switch in brain nutrient transporter expression in the rat
    Susan J Vannucci
    Department of Pediatrics, University, New York, New York 10032, USA
    Am J Physiol Endocrinol Metab 285:E1127-34. 2003
    ..of both human and rat brain is associated with a switch in metabolic fuel from a combination of glucose and ketone bodies in the immature brain to a nearly total reliance on glucose in the adult...
  34. ncbi Effects of beta-hydroxybutyrate on cognition in memory-impaired adults
    Mark A Reger
    Accera, Inc, Aurora, CO 80010, USA
    Neurobiol Aging 25:311-4. 2004
    ..Neurobiological evidence suggests that ketone bodies are an effective alternative energy substrate for the brain...
  35. pmc Decline in mitochondrial bioenergetics and shift to ketogenic profile in brain during reproductive senescence
    Jia Yao
    Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, CA 90033, USA
    Biochim Biophys Acta 1800:1121-6. 2010
    ..Herein, we sought to determine the impact of reproductive senescence on mitochondrial function in the normal non-transgenic (nonTg) and 3xTgAD female mouse model of AD...
  36. ncbi Pathways and control of ketone body metabolism: on the fringe of lipid biochemistry
    Toshiyuki Fukao
    Department of Pediatrics, Gifu University School of Medicine, Gifu 500, Japan
    Prostaglandins Leukot Essent Fatty Acids 70:243-51. 2004
    b>Ketone bodies become major body fuels during fasting and consumption of a high-fat, low-carbohydrate (ketogenic) diet. Hyperketonemia is associated with potential health benefits...
  37. doi Fibroblast growth factor 21 regulates lipolysis in white adipose tissue but is not required for ketogenesis and triglyceride clearance in liver
    Yuhei Hotta
    Department of Genetic Biochemistry, Kyoto University Graduate School of Pharmaceutical Sciences, Sakyo, Kyoto 606 8501, Japan
    Endocrinology 150:4625-33. 2009
    ..The present results indicate that Fgf21 regulates lipolysis in adipocytes in response to the metabolic state but is not required for ketogenesis and triglyceride clearance in the liver...
  38. ncbi The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism
    Richard L Veech
    Laboratory of Membrane Biochemistry and Biophysics, National Institutes of Alcoholism and Alcohol Abuse, 12501 Washington Ave, Rockville, MD 20850, USA
    Prostaglandins Leukot Essent Fatty Acids 70:309-19. 2004
    ..New diets comprised of ketone bodies themselves or their esters may obviate this present difficulty.
  39. ncbi A review of low-carbohydrate ketogenic diets
    Eric C Westman
    Department of Medicine, Duke University Medical Center, Box 50, Suite 200 B Wing, 2200 West Main Street, Durham, NC 27705, USA
    Curr Atheroscler Rep 5:476-83. 2003
    ..This review summarizes the physiology and recent clinical studies regarding this type of diet...
  40. ncbi Chronic exposure to beta-hydroxybutyrate impairs insulin action in primary cultures of adult cardiomyocytes
    A Tardif
    Department of Medicine, Research Center, , University of Montreal, Montreal H2W 1T8, Canada
    Am J Physiol Endocrinol Metab 281:E1205-12. 2001
    Type 1 and type 2 diabetic patients often show elevated plasma ketone body concentrations. Because ketone bodies compete with other energetic substrates and reduce their utilization, they could participate in the development of insulin ..
  41. ncbi Ketone body synthesis in the brain: possible neuroprotective effects
    Manuel Guzman
    Department of Biochemistry and Molecular Biology I, School of Biology, Complutense University, 28040 Madrid, Spain
    Prostaglandins Leukot Essent Fatty Acids 70:287-92. 2004
    b>Ketone bodies make an important contribution to brain energy production and biosynthetic processes when glucose becomes scarce...
  42. doi Energy substrate availability as a determinant of neuronal resting potential, GABA signaling and spontaneous network activity in the neonatal cortex in vitro
    Carl D Holmgren
    INMED INSERM U901, Universite de la Mediterranee, Marseille, France
    J Neurochem 112:900-12. 2010
    ..Complementing glucose with ketone bodies, pyruvate or lactate resulted in a significant hyperpolarization of both E(m) and E(GABA), and induced a ..
  43. doi Depolarizing actions of GABA in immature neurons depend neither on ketone bodies nor on pyruvate
    Roman Tyzio
    INSERM, Unité 901 Institut de Neurobiologie de Méditerranée, 13273 Marseille, France
    J Neurosci 31:34-45. 2011
    ..There is no need to alter conventional glucose enriched artificial CSF to investigate GABA signals in the developing brain...
  44. doi Effects of insulin on ketogenesis following fasting in lean and obese men
    Maarten R Soeters
    Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands
    Obesity (Silver Spring) 17:1326-31. 2009
    The ketone bodies (KBs) D-3-hydroxybutyrate (D-3HB) and acetoacetate (AcAc) play a role in starvation and have been associated with insulin resistance...
  45. doi GABA depolarizes immature neocortical neurons in the presence of the ketone body ß-hydroxybutyrate
    Knut Kirmse
    Experimentelle Neurologie, Hans Berger Klinik für Neurologie, Universitatsklinikum Jena, 07747 Jena, Germany
    J Neurosci 30:16002-7. 2010
    ..Our data thereby support the general concept of an excitatory-to-inhibitory switch of GABA action during early development...
  46. doi GABA action in immature neocortical neurons directly depends on the availability of ketone bodies
    Sylvain Rheims
    INMED INSERM U901, Universite de la Mediterranee, Marseille, France
    J Neurochem 110:1330-8. 2009
    ..rodent brain relies to a large extent on metabolic pathways alternate to glucose such as the utilization of ketone bodies (KBs). However, how KBs affect neuronal excitability is not known...
  47. ncbi Ketogenic diet, amino acid metabolism, and seizure control
    M Yudkoff
    Division of Child Development and Rehabilitation, Children s Hospital of Philadelphia, 34th St and Civic Center Blvd, Philadelphia, PA 19104, USA
    J Neurosci Res 66:931-40. 2001
    ..of amino acid metabolism occur as the system evolves from a glucose-based fuel economy to one that utilizes ketone bodies as metabolic substrates. We consider mechanisms by which such changes might lead to the antiepileptic effect.
  48. doi Ketone bodies as a therapeutic for Alzheimer's disease
    Samuel T Henderson
    Accera, Inc, Broomfield, Colorado 80021, USA
    Neurotherapeutics 5:470-80. 2008
    ..One promising approach is to supplement the normal glucose supply of the brain with ketone bodies (KB), which include acetoacetate, beta-hydroxybutyrate, and acetone...
  49. ncbi Brain uptake and metabolism of ketone bodies in animal models
    Astrid Nehlig
    INSERM U 405, Faculty of Medicine, 11, rue Humann, 67085 Strasbourg Cedex, France
    Prostaglandins Leukot Essent Fatty Acids 70:265-75. 2004
    ..During the period of lactation, the rate of uptake and metabolism of the two ketone bodies, beta-hydroxybutyrate and acetoacetate is high...
  50. ncbi Ketone bodies are protective against oxidative stress in neocortical neurons
    Do Young Kim
    Barrow Neurological Institute and St Joseph s Hospital and Medical Center, Phoenix, Arizona 85013, USA
    J Neurochem 101:1316-26. 2007
    b>Ketone bodies (KB) have been shown to prevent neurodegeneration in models of Parkinson's and Alzheimer's diseases, but the mechanisms underlying these effects remain unclear. One possibility is that KB may exert antioxidant activity...
  51. pmc Neuroprotective and disease-modifying effects of the ketogenic diet
    Maciej Gasior
    Epilepsy Research Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland 20892 3702, USA
    Behav Pharmacol 17:431-9. 2006
    ..These observations are supported by studies in animal models and isolated cells that show that ketone bodies, especially beta-hydroxybutyrate, confer neuroprotection against diverse types of cellular injury...
  52. pmc beta-Hydroxybutyrate fuels synaptic function during development. Histological and physiological evidence in rat hippocampal slices
    Y Izumi
    Department of Psychiatry, Washington University School of Medicine, St Louis, Missouri 63110, USA
    J Clin Invest 101:1121-32. 1998
    To determine whether ketone bodies sustain neuronal function as energy substrates, we examined the effects of beta-hydroxybutyrate (betaHB) on synaptic transmission and morphological integrity during glucose deprivation in rat ..
  53. ncbi Changes in insulin, glucose and ketone bodies, but not leptin or body fat content precede restoration of luteinising hormone secretion in ewes
    L A Szymanski
    Lehigh University, Bethlehem, PA, USA
    J Neuroendocrinol 19:449-60. 2007
    ..Prior to the initial LH pulses seen in Re-Fed ewes, plasma ketone bodies first fell and then rose to levels significantly above those in Restricted ewes...
  54. ncbi Blood ketone bodies in patients with recent-onset type 1 diabetes (a multicenter study)
    Francesco Prisco
    Department of Pediatrics, Second University of Naples, Naples, Italy
    Pediatr Diabetes 7:223-8. 2006
    Insulin deficiency with glucagon excess leads to the release of ketone bodies (KBs) by the liver and excretion in the urine. So far, only KB monitoring in urine has been used during assessment of children with diabetes...
  55. ncbi Measurement of beta-hydroxybutyrate in acute hyperketonemia in human brain
    J W Pan
    Department of Neurology, Albert Einstein College of Medicine, Bronx, New York 10461, USA
    J Neurochem 79:539-44. 2001
    ..The concentrations of BHB and lactate were both considerably lower in comparison with previous data acquired in fasted adult subjects. This suggests that up-regulation of the monocarboxylic acid transporter occurs with fasting...
  56. ncbi The protective effect of a ketogenic diet on kainic acid-induced hippocampal cell death in the male ICR mice
    Hae Sook Noh
    Department of Anatomy, College of Medicine, Gyeongsang National University, 92 Chilam dong, Chinju, 660 751, Kyungnam, South Korea
    Epilepsy Res 53:119-28. 2003
    ..These findings indicate that KD has an antiepileptic effect via a neuroprotective action that involves the inhibition of caspase-3-mediated apoptosis of hippocampal neurons...
  57. pmc Neuroprotection in diet-induced ketotic rat brain after focal ischemia
    Michelle A Puchowicz
    Department of Anatomy, School of Medicine, Case Western Reserve University, Cleveland, Ohio 44106 4930, USA
    J Cereb Blood Flow Metab 28:1907-16. 2008
    ....
  58. pmc Role of glucose and ketone bodies in the metabolic control of experimental brain cancer
    T N Seyfried
    Biology Department, Boston College, Chestnut Hill, MA 02467, USA
    Br J Cancer 89:1375-82. 2003
    ..This contrasts with normal brain tissue that can derive energy from both glucose and ketone bodies. We examined for the first time the potential efficacy of dietary therapies that reduce plasma glucose and ..
  59. pmc Ketoacids? Good medicine?
    George F Cahill
    Trans Am Clin Climatol Assoc 114:149-61; discussion 162-3. 2003
    ..Efforts are underway to prepare esters of beta-hydroxybutyrate which can be taken orally or parenterally to study its potential therapeutic applications...
  60. ncbi KTX 0101: a potential metabolic approach to cytoprotection in major surgery and neurological disorders
    Sharon L Smith
    RenaSci Consultancy Ltd, BioCity, Nottingham, NG1 1GF, UK
    CNS Drug Rev 11:113-40. 2005
    ..These issues are being addressed by designing and synthesizing orally bioavailable multimers of betaOHB with improved pharmacokinetics...
  61. ncbi Effect of acute hyperketonemia on the cerebral uptake of ketone bodies in nondiabetic subjects and IDDM patients
    G Blomqvist
    Uppsala University PET Centre, University Hospital Uppsala, S 75185 Uppsala, Sweden
    Am J Physiol Endocrinol Metab 283:E20-8. 2002
    ..For both groups, the utilization rate of ketone bodies was found to increase nearly proportionally with the plasma concentration of ketone bodies (1.0 +/- 0...
  62. doi Targeting energy metabolism in brain cancer with calorically restricted ketogenic diets
    Thomas N Seyfried
    Department of Biology, Boston College, Chestnut Hill, Massachusetts 02467, USA
    Epilepsia 49:114-6. 2008
    ..In contrast to normal neurons and glia, which evolved to metabolize ketone bodies as an alternative fuel to glucose under energy-restricted conditions, brain tumor cells are largely glycolytic ..
  63. ncbi Transport of ketone bodies and lactate in the sheep ruminal epithelium by monocarboxylate transporter 1
    Frank Muller
    Veterinär Physiologisches Institut, Universitat Leipzig, D 04103 Leipzig, Germany
    Am J Physiol Gastrointest Liver Physiol 283:G1139-46. 2002
    ..In conclusion, our data indicate that MCT1 is expressed in the stratum basale of the ruminal epithelium and may function as a main mechanism for removing ketone bodies and lactate together with H+ from the cytosol into the blood.
  64. ncbi Anticonvulsant mechanisms of the ketogenic diet
    Kristopher J Bough
    Center for Drug Evaluation and Research, Food and Drug Administration, Rockville, Maryland 20855, USA
    Epilepsia 48:43-58. 2007
    ..gleaned from experimental and clinical studies of the KD, and focus particular attention on the role that ketone bodies, fatty acids, and limited glucose may play in seizure control...
  65. ncbi Fatty acid oxidation and ketogenesis by astrocytes in primary culture
    N Auestad
    Division of Nutritional Sciences, UCLA School of Public Health
    J Neurochem 56:1376-86. 1991
    The oxidation of the fatty acids octanoate and palmitate to CO2 and the ketone bodies acetoacetate and D-(-)-3-hydroxybutyrate was examined in astrocytes that were prepared from cortex of 2-day-old rat brain and grown in primary culture ..
  66. pmc Hypometabolism as a therapeutic target in Alzheimer's disease
    Lauren C Costantini
    Accera Inc, Interlocken Crescent, Broomfield, CO 80021, USA
    BMC Neurosci 9:S16. 2008
    ..b>Ketone bodies are an efficient alternative fuel for cells that are unable to metabolize glucose or are 'starved' of glucose...
  67. ncbi D-beta-hydroxybutyrate protects dopaminergic SH-SY5Y cells in a rotenone model of Parkinson's disease
    Keiko Imamura
    Department of Neurology, Institute of Neurological Sciences, Faculty of Medicine, Tottori University, Yonago, Japan
    J Neurosci Res 84:1376-84. 2006
    ..b>Ketone bodies, the alternative energy source in the mammalian brain, appear to have therapeutic potential in PD.
  68. doi Antioxidant capacity contributes to protection of ketone bodies against oxidative damage induced during hypoglycemic conditions
    María L Haces
    Departamento de Neurociencias, Instituto de Fisiologia Celular, Universidad Nacional Autonoma de Mexico UNAM, Mexico D F, Mexico
    Exp Neurol 211:85-96. 2008
    b>Ketone bodies play a key role in mammalian energy metabolism during the suckling period...
  69. ncbi Beta-hydroxybutyrate levels in peripheral blood and ketone bodies supplemented in culture media affect the in vitro chemotaxis of bovine leukocytes
    W Suriyasathaporn
    Department of Herd Health and Reproduction, Faculty of Veterinary Medicine, Utrecht University, The Netherlands
    Vet Immunol Immunopathol 68:177-86. 1999
    The role of ketone bodies on chemotactic capacities of leukocytes was characterized in two experiments...
  70. ncbi Ketone body utilization for lipogenesis in the perfused liver of the obese Zucker rat
    M J Azain
    Cardiovascular Biology, Oklahoma Medical Research Foundation, Oklahoma City
    Horm Metab Res 22:561-5. 1990
    The purpose of these studies was to determine if the utilization of ketone bodies as a carbon source for lipogenesis could account for the decreased ketone body production by livers of obese Zucker rats, as well as contribute to the ..
  71. ncbi Perspectives on the metabolic management of epilepsy through dietary reduction of glucose and elevation of ketone bodies
    Amanda E Greene
    Boston College Biology Department, Chestnut Hill, Massachusetts, USA
    J Neurochem 86:529-37. 2003
    Brain cells are metabolically flexible because they can derive energy from both glucose and ketone bodies (acetoacetate and beta-hydroxybutyrate)...
  72. ncbi Free fatty acids, but not ketone bodies, protect diabetic rat hearts during low-flow ischemia
    L M King
    Department of Biochemistry, University of Oxford, Oxford OX1 3QU, United Kingdom
    Am J Physiol Heart Circ Physiol 280:H1173-81. 2001
    ..2 mM palmitate or the ketone bodies, 4 mM beta-hydroxybutyrate plus 1 mM acetoacetate, were subjected to 32 min of low-flow (0...
  73. ncbi Gender differences in postprandial ketone bodies in normolipidemic subjects and in untreated patients with familial combined hyperlipidemia
    C J M Halkes
    Department of Vascular Medicine, University Medical Center Utrecht, The Netherlands
    Arterioscler Thromb Vasc Biol 23:1875-80. 2003
    ..Postprandial ketone bodies reflect FFA oxidation in the liver, but the postprandial changes in male and female patients separately have ..
  74. ncbi Acetoacetate and beta-hydroxybutyrate in combination with other metabolites release insulin from INS-1 cells and provide clues about pathways in insulin secretion
    Michael J MacDonald
    Children Diabetes Center, Univesity of Wisconsin School of Medicine and Public Health, Madison, WI, USA
    Am J Physiol Cell Physiol 294:C442-50. 2008
    ..The pathways of their metabolism suggest that, in addition to producing ATP, the ketone bodies and KIC supply the acetate component and MMS supplies the oxaloacetate component of citrate...
  75. ncbi [Abnormal metabolism of fatty acids and ketone bodies in Duchenne muscular dystrophy, and the effect of biotin on these abnormalities]
    K Honke
    Department of Pediatrics, National Sanatorium Io Hospital, Ishikawa
    No To Hattatsu 29:13-8. 1997
    It has been reported that serum levels of ketone bodies often elevate in patients with Duchenne muscular dystrophy (DMD). The cause of this abnormal metabolism, however, has not been elucidated...
  76. ncbi Identity of SMCT1 (SLC5A8) as a neuron-specific Na+-coupled transporter for active uptake of L-lactate and ketone bodies in the brain
    Pamela M Martin
    Department of Biochemistry and Molecular Biology, Medical College of Georgia, Augusta, Georgia, USA
    J Neurochem 98:279-88. 2006
    ..Here, we show that the ketone bodies, beta-d-hydroxybutyrate and acetoacetate, and the branched-chain ketoacid, alpha-ketoisocaproate, are also ..
  77. ncbi Ketone bodies metabolism during ischemic and reperfusion brain injuries following bilateral occlusion of common carotid arteries in rats
    Mário Henrique Girão Faria
    Department of Physiology and Pharmacology, Federal University of Ceara Medical School, Brazil
    Acta Cir Bras 22:125-9. 2007
    To evaluate the in vivo alterations on ketone bodies metabolism after cerebral ischemia/reperfusion through an experimental model of brain ischemia induced by simple occlusion of common carotid arteries (CCAs) in Wistar rats.
  78. ncbi Real-time assessment of hepatic function is related to clinical outcome in critically ill patients after polytrauma
    Klaus Dresing
    Department of Trauma Surgery, Plastic and Reconstructive Surgery, University Medicine Goettingen, Georg August University, Robert Koch Strasse 40, D 37075 Gottingen, Germany
    Clin Biochem 40:1194-200. 2007
    ..The aim was to investigate the outcome MODS/MOF in critically ill patients with regard to early hepatic dysfunction...
  79. ncbi Effects of dietary soybean peptides on hepatic production of ketone bodies and secretion of triglyceride by perfused rat liver
    Shizuka Tamaru
    Department of Biochemistry and Applied Biosciences, Faculty of Agriculture, University of Miyazaki, Japan
    Biosci Biotechnol Biochem 71:2451-7. 2007
    ..There is a possibility that soybean peptides modulate triglyceride metabolism by changes in the hepatic contribution...
  80. ncbi Ketone bodies affect the enzymatic activity of macrophage migration inhibitory factor
    Janos Garai
    Department of Pathophysiology, University of Pecs, Medical School, Pecs, H 7624 Pecs, Szigeti u 12, Hungary
    Life Sci 77:1375-80. 2005
    ..Ketones of physiological importance - ketone bodies - also feature acidic CH groups and have been reported to exert certain anti-inflammatory effects...
  81. ncbi Neuronal-glial interactions in rats fed a ketogenic diet
    Torun Margareta Melø
    Department of Neuroscience, Norwegian University of Science and Technology, NTNU, N 7489 Trondheim, Norway
    Neurochem Int 48:498-507. 2006
    ..However, during periods of fasting and consumption of a high fat, low carbohydrate (ketogenic) diet, ketone bodies become major brain fuels...
  82. ncbi Effect of weight loss and ketosis on postprandial cholecystokinin and free fatty acid concentrations
    Supornpim Chearskul
    Department of Physiology, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand
    Am J Clin Nutr 87:1238-46. 2008
    ..Weight regain after weight loss may not be due primarily to voluntary return to social habits but may be explained by changes in peripheral hormonal signals activating hunger and encouraging feeding behavior...
  83. ncbi Role of ketone bodies in perinatal myocardial energy metabolism
    B Bartelds
    Department of Pediatrics, University of Groningen, Beatrix Children s Hospital and Groningen University Institute for Drug Exploration, P O Box 30001, NL 9700 RB Groningen, The Netherlands
    Biochem Soc Trans 29:325-30. 2001
    ..The oxidation of ketone bodies increases after birth in relation to an increase in supply...
  84. doi Excitatory action of GABA on immature neurons is not due to absence of ketone bodies metabolites or other energy substrates
    Yehezkel Ben-Ari
    INMED, INSERM U901, Marseille, France
    Epilepsia 52:1544-58. 2011
    ..that γ-aminobutyric acid (GABA) excites neonatal neurons in conventional glucose-perfused slices but not when ketone bodies metabolites, pyruvate, and/or lactate are added, suggesting that the excitatory actions of GABA are due to ..
  85. ncbi Chronic exposure to ketone bodies impairs glucose uptake in adult cardiomyocytes in response to insulin but not vanadate: the role of PI3-K
    Amélie Pelletier
    Montreal Diabetes Research Centre, Centre hospitalier de l Université de Montréal CHUM Hôtel Dieu, 3850 St Urbain, Montreal, Que, Canada, H2W 1T7
    Mol Cell Biochem 296:97-108. 2007
    ..In conclusion, ketone bodies promote insulin resistance probably through decreased activation of the PI3-K/PKB signaling cascade...
  86. ncbi Utilization of ketone bodies by the rat liver, brain and heart in chronic alcohol intoxication
    - Lukivskaya OYa
    Institute of Biochemistry, Byelorussian Academy of Sciences, Grodno
    Alcohol Alcohol 28:431-6. 1993
    ..The data obtained indicate both disturbed ketone body utilization and increased importance of acetate produced from ethanol as an energy source in the heart during long-term ethanol treatment...
  87. ncbi Safe and effective use of the ketogenic diet in children with epilepsy and mitochondrial respiratory chain complex defects
    Hoon Chul Kang
    Department of Pediatrics and Epilepsy Center, Sanggye Paik Hospital, Inje University College of Medicine, Seoul, Korea
    Epilepsia 48:82-8. 2007
    ..To evaluate the clinical efficacy and safety of the ketogenic diet (KD) for patients with intractable childhood epilepsy and mitochondrial respiratory chain (RC) complex defects...
  88. ncbi Gestational diabetes exhibits lack of carnitine deficiency despite relatively low carnitine levels and alterations in ketogenesis
    Kalliopi I Pappa
    Department of Obstetrics and Gynecology, University of Crete School of Medicine, Heraklion, Greece
    J Matern Fetal Neonatal Med 17:63-8. 2005
    ..The objective of this paper was to delineate more systematically the role of the carnitine shuttle system in normal pregnancy and in gestational diabetes...
  89. ncbi Distinct effects of ketone bodies on down-regulation of cell surface insulin receptor and insulin receptor substrate-1 phosphorylation in adrenal chromaffin cells
    Hiroki Yokoo
    Department of Pharmacology, Miyazaki Medical College, Miyazaki, Japan
    J Pharmacol Exp Ther 304:994-1002. 2003
    ..These results suggest that chronic treatment with acetoacetate selectively down-regulated the density of cell surface functional IR via lowering IR mRNA levels and IR synthesis, thereby retarding insulin-induced activation of IRS-1...
  90. ncbi Oral beta-hydroxybutyrate supplementation in two patients with hyperinsulinemic hypoglycemia: monitoring of beta-hydroxybutyrate levels in blood and cerebrospinal fluid, and in the brain by in vivo magnetic resonance spectroscopy
    Barbara Plecko
    Division of Metabolism and Pediatric Neurology, Department of Pediatrics, University Hospital of Graz, Austria
    Pediatr Res 52:301-6. 2002
    ..The neuroprotective effect of endogenous ketone bodies is evidenced by animal and human studies, but knowledge about exogenous supply is limited...
  91. ncbi Effects of beta-hydroxybutyric acid on bovine milk leukocytes function in vitro
    S I Cerone
    Departamento de Fisiopatologia, Facultad de Cs Veterinarias, UNCPBA, Tandil, Buenos Aires, Argentina
    Gen Physiol Biophys 26:14-9. 2007
    ..particulate agents decreased significantly in 33 and 26%, respectively, compared with cells incubated without ketone bodies. This result suggests a possible fault in the microbicidal oxidative activity...
  92. ncbi Point of care blood ketone testing of diabetic patients in the emergency department
    Firat Bektas
    Department of Emergency Medicine, School of Medicine, University of Akdeniz, Antalya, Turkey
    Endocr Res 30:395-402. 2004
    ..This device can be used as a reliable diagnostic test to detect emergency metabolic problems in diabetic patients, such as diabetic ketosis or ketoacidosis...
  93. ncbi The ketogenic diet
    Eileen P G Vining
    Adv Exp Med Biol 497:225-31. 2002
    ..One of the most significant trends in therapy has been the renewed popularity of the ketogenic diet. Dr. Vining discusses the history of the diet, its possible mechanisms of action and its clinical efficacy...
  94. ncbi Is a fast necessary when initiating the ketogenic diet?
    Elaine C Wirrell
    Division of Neurology, University of Calgary, Alberta Children s Hospital, Calgary, AB
    J Child Neurol 17:179-82. 2002
    ..The ketogenic diet can be effectively initiated without a fast in children with epilepsy. Time to ketosis and diet efficacy are similar to protocols that use a fast...
  95. ncbi Clinical aspects of the ketogenic diet
    Adam L Hartman
    The John M Freeman Pediatric Epilepsy Center, Johns Hopkins Medical Institutions, Baltimore, Maryland 21287, USA
    Epilepsia 48:31-42. 2007
    ..Ketogenic diets now are being used for diseases other than epilepsy. This critical analysis of the diet should provide the impetus for further clinical and basic research into the diet's application and mechanisms of action...
  96. ncbi Basal ganglia injury as a complication of the ketogenic diet
    Jay C Erickson
    Department of Neurology, Walter Reed Army Medical Center, Washington DC 20307, USA
    Mov Disord 18:448-51. 2003
    ..Basal ganglia injury and extrapyramidal movement abnormalities are potential complications of the ketogenic diet. Concomitant use of valproate or a latent inborn error of metabolism may be risk factors for these rare complications...
  97. ncbi Influence of the ketogenic diet on 24-hour electroencephalogram in children with epilepsy
    Sten Remahl
    Department of Neurophysiology, Neuroscience Institution, Karolinska Hospital, Stockholm, Sweden
    Pediatr Neurol 38:38-43. 2008
    ..This improvement was seen in both seizure-reduction responders and nonresponders, and was not predictive of response to treatment...
  98. ncbi Hypocalcemia reduces endogenous glucose production in hyperketonemic sheep
    C Schlumbohm
    Department of Physiology, School of Veterinary Medicine, Bischofsholer Damm 15 102, 30173 Hannover, Germany
    J Dairy Sci 86:1953-62. 2003
    ..We concluded that hypocalcemia does not promote the onset of pregnancy toxemia per se but will facilitate the development of the disease when it is present in combination with hyperketonemia...
  99. ncbi Hyperketonemia impairs glucose metabolism in pregnant and nonpregnant ewes
    C Schlumbohm
    Department of Physiology, School of Veterinary Medicine, Bischofsholer Damm 15 102, 30173 Hannover, Germany
    J Dairy Sci 87:350-8. 2004
    ..This effect of hyperketonemia may invoke sustained hypoglycemia and may render the ewe into a vicious cycle that probably makes the animal refractory to treatment in most cases...
  100. ncbi The influence of small doses of paracetamol on rabbit liver
    Izabela Maciejewska-Paszek
    Department of Food and Nutrition, Medical University of Silesia, 41 200 Sosnowiec, Jagiellońska 4 Street, Katowice, Poland
    Exp Toxicol Pathol 59:139-41. 2007
    ..It was determined by measuring the concentration of ketone bodies and arterial ketone body ratio (AKBR) value...
  101. doi Ketogenic diets cause opposing changes in synaptic morphology in CA1 hippocampus and dentate gyrus of late-adult rats
    Marta Balietti
    Neurobiology of Aging Laboratory, INRCA Research Department, Ancona, Italy
    Rejuvenation Res 11:631-40. 2008
    ..different susceptibility to aging processes: OML DG is less vulnerable than SM CA1, and the reactivation of ketone bodies uptake and catabolism might occur more efficiently in this region, allowing the exploitation of their peculiar ..

Research Grants69

  1. Pyruvate Dehydrogenase kinase as Therapeutic Target for Hepatic Steatosis, Obesit
    Robert A Harris; Fiscal Year: 2012
    ..sensitivity, hepatic steatosis, adiposity, branched chain amino acids (BCAAs), free fatty acids (FFAs), ketone bodies, triacylglcyerols (TAG), cholesterol, blood pH, and markers of inflammation and oxidative stress in mice fed a ..
  2. Energy Balance During Ketosis in Rat Brain
    JOSEPH CHARLES LAMANNA; Fiscal Year: 2010
    DESCRIPTION (provided by applicant): The uptake and metabolism of ketone bodies in brain have been of interest to researchers and clinicians for decades but how they affect the coupling of blood flow and glucose metabolism, especially ..
  3. Glutamate-Glutamine Metabolism in Primary Human Brain Tumors
    Anne Williamson; Fiscal Year: 2010
    ..In Specific Aim 2, we propose that changing the fuel balance to one favoring fatty acids and ketone bodies with reduced glucose/glycogen availability will reduce extracellular glutamate release by increasing glutamate ..
  4. Epigenomic regulation of metabolism in muscle by circadian clock and environment
    Zheng Sun; Fiscal Year: 2013
    ..I will characterize mitochondrial function and trace metabolic fluxes through lipid, ketone bodies, and amino acids catabolism, including the anaplerotic purine nucleotide cycle, in exercising animals as well ..
  5. Regulation of Carbohydrate Metabolism and Lipogenesis
    Kosaku Uyeda; Fiscal Year: 2013
    ..We have identified the metabolites as ketone bodies. To characterize the metabolites further we propose to (1) determine the biochemical mechanism by which they ..
  6. Angiogenic Response to Hypoxia and Ketosis in Rat Brain
    JOSEPH CHARLES LAMANNA; Fiscal Year: 2012
    ..We intend to determine if similar responses can be elicited in the ketotic, aged rat brain. Ketone bodies are alternate energy substrates to glucose and are signaling molecules that stabilize glucose metabolism by ..
  7. Imaging cellular energy metabolism in brain slices using fluorescent biosensors
    REBECCA ANNE MONGEON; Fiscal Year: 2013
    ..It is generally believed that ketone bodies, abundant in the blood of dieting patients, replace glucose as the primary substrate for brain metabolism, and ..
  8. The Role of Adenosine in Ketogenic Diet Therapy
    Susan A Masino; Fiscal Year: 2013
    ..and neurochemical techniques will quantify changes in energy molecules, adenosine, adenosine receptors, and ketone bodies (Aim 1)...
  9. Metabolic requirements of adult neural stem cells
    Philip J Horner; Fiscal Year: 2012
    ..We hypothesize that adult neural stem cells are dependent upon metabolism of fatty acids or ketone bodies for metabolic and mitotic activity...
  10. Metabolic Mechanisms of Functional Neuroprotection in Epileptic Brain
    Do Young Kim; Fiscal Year: 2013
    ..b>Ketone bodies have recently been shown to exert neuroprotective activity in several models of neurological disease...
  11. Cellular mechanisms of dietary therapy for epilepsy
    GARY I YELLEN; Fiscal Year: 2013
    ..We observed that KATP channels in neurons could be activated synergistically by neuronal activity and by ketone bodies (which are an alternative fuel used by the brain on the ketogenic diet)...
  12. Metabolic control of neuronal activity by fuel substrate switching
    GARY I YELLEN; Fiscal Year: 2013
    ..BAD's metabolic function can lead to reduced mitochondrial oxidation of glucose and enhanced oxidation of ketone bodies, in both neurons and astrocytes...
  13. Adaptations of Brain Energy Metabolism to Hypoglycemia
    RAIMUND INGO HERZOG; Fiscal Year: 2013
    ..One group of fuels that fulfill these criteria are ketone bodies and medium chain fatty acids...
  14. Brain Acetate and Ethanol Metabolism in Alcohol Dependence and Abuse
    Graeme F Mason; Fiscal Year: 2013
    ..primary fuel for brain energy metabolism, so in hypoglycemia the brain relies increasingly on blood lactate, ketone bodies, and acetate, all of which cross the blood-brain barrier by the same monocarboxylic acid transporter...
  15. Role of Acetate in Heavy Drinking
    Graeme F Mason; Fiscal Year: 2010
    ..primary fuel for brain energy metabolism, so in hypoglycemia the brain relies increasingly on blood lactate, ketone bodies, and acetate, all of which cross the blood-brain barrier by the same monocarboxylic acid transporter...
  16. Reprogramming Neural Energy Metabolism for Control of Excitability and Seizures
    GARY I YELLEN; Fiscal Year: 2011
    ..dependent mechanism that enables metabolism of glucose as compared with other carbon substrates such as ketone bodies and fatty acids...
  17. KETONE BODY METABOLISM AND INTEGRATED METABOLIC HOMEOSTASIS
    Peter A Crawford; Fiscal Year: 2013
    DESCRIPTION (provided by applicant): Ketone bodies are an avidly oxidized cellular fuel source, produced in abundance during the neonatal period, starvation, decompensated diabetes, and by adherence to low-carbohydrate (e.g...
  18. Metabolic and KATP channel regulation of the cortical slow oscillation
    Andrew Lutas; Fiscal Year: 2013
    ..of cellular metabolism to the regulation of the oscillation by providing different energy fuels, particularly ketone bodies that may alter K{ATP} channel activity...
  19. ENERGY REQUIREMENT OF NEURONS AFTER BRAIN INJURY
    Stefan Lee; Fiscal Year: 2009
    ..g., pyruvate, lactate, glutamine, ketone bodies or Krebs cycle intermediates? Does this come at the expense of more free radical production? iv) What is the ..
  20. Acetone metabolism in Helicobacter pylori
    Timothy Hoover; Fiscal Year: 2004
    ..Acetone is produced in the body upon the spontaneous decarboxylation of acetoacetate, one of the ketone bodies produced by the liver and used as an energy source when glucose is not readily available...
  21. MITOCHONDRIAL SHORT CHAIN 3-OH-ACYL-COA DEHYDROGENASES
    Arnold Strauss; Fiscal Year: 2003
    ..of energy in highly oxidative mammalian tissues and is essential for intermediary metabolism and production of ketone bodies in liver...
  22. Fatty Liver Disease and Hepatic Energy Homostatis in SH*
    Jeanne Clark; Fiscal Year: 2005
    ..and collect additional data including liver enzymes (0, 6, 12 mo.), MRI Spectroscopy (0, 12 mo.), and ketone bodies, insulin levels, and proinflammatory cytokines (0, 12 mo...
  23. CNS DELIVERY OF ALKANOATE ANTIEPILEPTICS
    Danny Shen; Fiscal Year: 1999
    ..the brain capillary endothelium by the monocarboxylic acid (MCA) transporter, which mediates the exchange of ketone bodies and lactate between blood and brain...
  24. DEVELOPING BRAIN: EFFECTS OF NUTRITIONAL IMBALANCES
    GOVIND DHOPESHWARKAR; Fiscal Year: 1980
    ..of radioactive precursors such as glucose, acetate, amino acids (such as leucine and isoleucine) and ketone bodies such as B hydroxybutyrate to gain information on lipogenesis...
  25. Human Brain Metabolism in Ketosis
    Jullie Pan; Fiscal Year: 2004
    It is well known that the brain can switch from its primary fuel of glucose to ketone bodies under states of fasting, vigorous exercise, specific diets as well as a number of clinical disorders...
  26. CALORIC RESTRICTION IN TUMOR PROMOTION: MECHANISMS
    David Kritchevsky; Fiscal Year: 1991
    ..proline, octanoate, and beta hydroxybutyrate (as representatives of carbohydrate, protein, fat and ketone bodies, respectively)...
  27. REGULATING MYOCARDIAL FATTY ACID OXIDATION IN DIABETES
    GEORGE COOK; Fiscal Year: 2003
    ..preferentially uses fatty acids as an energy source for muscle contraction, although it can utilize glucose, ketone bodies and lactate...
  28. MODULATION OF MONOCARBOXYLIC ACID TRANSPORTERS IN BRAIN
    LESTER DREWES; Fiscal Year: 2004
    ..and early development (newborn or suckling neonates), monocarboxylates such as lactate, pyruvate and ketone bodies may be extracted from the blood and used by the brain as fuels...
  29. ESTROGEN-GLUCAGON INTERACTIONS IN HEPATIC METABOLISM
    IRA WEINSTEIN; Fiscal Year: 1980
    ..of cAMP in the liver and serum, and the serum concentrations of glucose, free fatty acids, triglyceride, ketone bodies and insulin...
  30. METABOLISM IN THE NONHUMAN PRIMATE AND OVINE FETUS
    Lynne Levitsky; Fiscal Year: 1991
    ..Total lipogenesis and lipogenesis from ketone bodies will be measured in the baboon fetus...
  31. MRI OF BODY FAT, OVULATION AND ESTROGEN METABOLISM
    ROSE FRISCH; Fiscal Year: 1990
    ..body temperature; 4) The extent of 2-hydroxylation of 17 beta-Estradiol by radiometric analysis; 5) fasting ketone bodies and free fatty acids...
  32. EFFECTS OF INSULIN ON THE CATABOLIC RESPONSE TO TRAUMA
    Palmer Bessey; Fiscal Year: 1991
    ..intracellular skeletal muscle amino acid concentration; concentration of free fatty acids and ketone bodies; and hormone concentration...
  33. PATHWAYS OF ENERGY METABOLISM IN MALIGNANCY IN VIVO
    LEONARD SAUER; Fiscal Year: 1991
    ..or diabetes increased arterial blood concentrations of glycerol, free fatty acids, triglycerides and ketone bodies, increased tumor utilization of these nutrients and increased the rate of tumor DNA synthesis and growth 2 to ..
  34. CHARACTERIZATION & THERAPY OF NEW FAT OXIDATION DEFECTS
    Charles Roe; Fiscal Year: 1991
    ..Since these disorders will share an inability to produce ketone bodies normally, treatment strategies involving restoration of this fuel source will be attempted with RS-1, 3-..
  35. HYPOTHALAMIC REGULATION OF FOOD INTAKE
    ALBERT DEBONS; Fiscal Year: 1980
    ..thioglucose-induced neural changes in the ventromedial hypothalamus on blood levels of glucagon, insulin and ketone bodies. We have also found that hypothalamic hyperphagia is dependent on the presence of the adrenal glands; ..
  36. Cellular mechanisms of ketogenic diet epilepsy treatment
    JAMES BERG; Fiscal Year: 2006
    ..that is currently being explored in Gary Yellen's lab is that the diet works via an effect of circulating ketone bodies on neuronal excitability...
  37. GABAergic Inhibition and the Ketogenic Diet
    JONG RHO; Fiscal Year: 2007
    ..The hallmark feature of the KD is the production of the ketone bodies by the liver...
  38. In vivo Substrate Utilization in the Newborn Rat Brain
    Raghavendra Rao; Fiscal Year: 2006
    ..An in vivo evaluation of substrate preference and utilization, specifically those of glucose, ketone bodies, and brain glycogen, during hypoglycemia is essential to optimize therapeutic interventions for neonatal ..
  39. THE ROLE OF GLUT4 IN THE PATHO OF DIABETIC CARDIOMYOPA
    EVAN ABEL; Fiscal Year: 1999
    ..body glucose tolerance and insulin sensitivity, and cardiac metabolic fuels of lactate, free fatty acids, ketone bodies, and amino acids differ from the wild type...
  40. HMG-COA CYCLE CONTROL IN NORMAL AND DIABETIC LIVER
    HENRY MIZIORKO; Fiscal Year: 1999
    ..Finally, the enzyme that activates ketone bodies for use in biosynthesis, acetoacetyl-CoA synthetase, is poorly characterized...
  41. Fatty acid metabolism and DGAT1 deficiency
    CLAUDIO VILLANUEVA; Fiscal Year: 2006
    ..oxidation by measuring the formation of [1-14C] CO2 from [1-1"C] palmitate and measuring the serum levels of ketone bodies. Aim 2.2: Determine if there is increased expression of genes implicated in fatty acid oxidation. Aim 2...
  42. KETOGENIC DIET AND BRAIN AMINO ACID METABOLISM
    Marc Yudkoff; Fiscal Year: 2002
    ..The PI hypothesizes, based on their preliminary data, that one reason the ketone bodies (3-OH-butyrate and acetoacetate) are so effective in controlling seizures is that they increase the brain ..
  43. GLYCOSPHINGOLIPIDS IN MURINE NEURODEGENERATIVE DISEASES
    THOMAS SEYFRIED; Fiscal Year: 2004
    ..Since there are no effective treatments for human ganglioside storages disease, the proposed research could offer a novel therapy for the early intervention of these neurodegenerative disorders. ..
  44. Glycosphingolipid Effects on Brain Tumor Angiogenesis
    THOMAS SEYFRIED; Fiscal Year: 2006
    ..The proposed research will better define the relationship between gangliosides and tumor angiogenesis and can lead to new experimental strategies for managing brain tumors. ..
  45. GLYCOSPHINGOLIPIDS IN MURINE NEURODEGENERATIVE DISEASES
    THOMAS SEYFRIED; Fiscal Year: 2009
    ..The proposed studies will provide essential information on combinatorial therapies for the ganglioside storage diseases and will have translational benefit to the clinic. ..
  46. Career Development in Diabetes for Pediatric Endocrinolo
    Lori Laffel; Fiscal Year: 2007
    ..abstract_text> ..
  47. Training Grant in Diabetes for Pediatric Endocrinologis*
    Lori Laffel; Fiscal Year: 2006
    ..We have demonstrated the ability to attract highly qualified candidates to our training program and look forward to meeting the challenge of training and developing successful pediatric endocrinologists in diabetes research. ..
  48. Hershey Conference on Developmental Brain Injury
    SUSAN VANNUCCI; Fiscal Year: 2008
    ..abstract_text> ..
  49. OPTIMIZING ADHERENCE AND GLYCEMIA IN YOUTH WITH NEW IDDM
    Lori Laffel; Fiscal Year: 2001
    ....
  50. Age-Dependent Ketone Metabolism After Brain Injury
    Mayumi Prins; Fiscal Year: 2007
    While glucose remains the primary cerebral metabolic substrate under normal conditions, shifting to ketone bodies is a common form of metabolic adaptation demonstrated under conditions of increased energy demands or decreased glucose ..
  51. Hypoglycemia and the Developing Brain
    SUSAN VANNUCCI; Fiscal Year: 2005
    ....
  52. Ketosis, Vascular Inflammation and Its Therapy in Type 1 Diabetic Patients
    Sushil K Jain; Fiscal Year: 2010
    ..The long-term goal is to understand the role of ketosis in CVD and to discover a relatively low-cost dietary supplement that could be used as an adjuvant therapy for CVD prevention in type 1 diabetes. ..
  53. Adjuvant Therapy for Vascular Inflammation in Diabetes
    Sushil Jain; Fiscal Year: 2006
    ..abstract_text> ..
  54. REGULATION OF CEREBRAL BLOOD FLOW BY ATP
    Damir Janigro; Fiscal Year: 2003
    ..2) To elucidate the mechanisms of potassium-mediated dilations in vivo. These studies will allow better understanding on neuronal-vascular interactions and will open new perspectives for the treatment of neurological diseases. ..
  55. Clinical Performance Measures & Outcomes in Adolescents
    Susan Furth; Fiscal Year: 2005
    ..abstract_text> ..
  56. Walnuts vs. Walnut-Oil, Glucose Homeostasis, PCOS
    Sidika Kasim Karakas; Fiscal Year: 2007
    ..unreadable] [unreadable]..
  57. STRUCTURE AND SPECIFICITY OF LIPOGENIC ENZYMES
    Stuart Smith; Fiscal Year: 2008
    ..abstract_text> ..
  58. NITROGEN HETEROCYCLES: METABOLIC EFFECTS AND TOXICITY
    Raymond F Novak; Fiscal Year: 2010
    ....
  59. ANTIDEPRESSANT THERAPY AND HYPOGLYCEMIA
    Dianne Lattemann; Fiscal Year: 2006
    ..non-diabetic rats. The results of these studies will provide new knowledge that ultimately may assist primary physicians in determining the most advantageous treatment for their diabetic patients with depression. ..
  60. Human mitochondrial fatty acid synthase
    Stuart Smith; Fiscal Year: 2009
    ..Elucidation of the role of the mitFAS system in mitochondrial function may aid in understanding the etiology of these disorders. ..
  61. CNS Stress Pathways and the Development of Acute HAAF
    Dianne Lattemann; Fiscal Year: 2003
    ..abstract_text> ..
  62. Epileptogenicity in the Developing Brain
    Raman Sankar; Fiscal Year: 2007
    ..Our findings will provide the basis for future neuroprotective interventions targeting the developing brain at different stages of status epilepticus in order to interrupt the course of the epileptogenic process. ..
  63. The modulation of adenosine by temperature, oxygen and glucose
    SUSAN MASINO; Fiscal Year: 2008
    ..unreadable] [unreadable]..
  64. CONTROL OF FEEDING BEHAVIOR--HEPATIC AFFERENT SIGNALING
    CHARLES HORN; Fiscal Year: 2002
    ..Results from this project may contribute to a better understanding of metabolic stimuli that are sensed by the nervous system, and may elucidate neural controls that are involved in obesity, anorexia, and diabetes. ..
  65. Nutritional Treatment of Fat Oxidation Defect in Mice
    Henri Brunengraber; Fiscal Year: 2009
    ..We hypothesize that heptanoate, and the C5-ketone bodies derived from its initial hepatic metabolism, exert their beneficial effects by (i) providing propionyI-CoA, an ..
  66. Xenobiotics and Breast Epithelial Cell-ECM Signaling
    Raymond Novak; Fiscal Year: 2005
    ..The results of this proposal will provide novel information regarding chemical-mediated effects in breast epithelial cells and seminal data on fundamental cellular changes in human proliferative breast disease. ..
  67. Molecular and Cellular Toxicology
    Melissa Runge Morris; Fiscal Year: 2008
    ....