The contribution of ketone bodies to basal and activity-dependent neuronal oxidation in vivo

Journal of Cerebral Blood Flow and Metabolism

Volumn 34, Issue 7, 2014, Pages 1233-1242

  Chowdhury, Golam M I ^a   Jiang, Lihong ^a   Rothman, Douglas L ^a   Behar, Kevin L ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

13C isotopes; glucose utilization; glutamate glutamine cycle; ketone body utilization; neuroenergetics; nuclear magnetic resonance spectroscopy

Indexed keywords

3 HYDROXYBUTYRIC ACID; ACETYL COENZYME A; CARBON 13; GLUCOSE; HALOTHANE; KETONE BODY; PENTOBARBITAL; PYRUVIC ACID; TRICARBOXYLIC ACID;

AMINO ACID BRAIN LEVEL; ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CONTROLLED STUDY; EX VIVO STUDY; IN VIVO STUDY; MALE; NERVE CELL; NEUROTRANSMISSION; NONHUMAN; OXIDATION; PRIORITY JOURNAL; RAT;

ANIMALS; BRAIN; KETONE BODIES; MAGNETIC RESONANCE SPECTROSCOPY; MALE; NEURONS; OXIDATION-REDUCTION; OXIDATIVE PHOSPHORYLATION; RATS; RATS, SPRAGUE-DAWLEY;

EID: 84903759041     PISSN: 0271678X     EISSN: 15597016     Source Type: Journal    
DOI: 10.1038/jcbfm.2014.77     Document Type: Article

References (40)

1. Lopes-Cardozo M, Larsson OM, Schousboe A. Acetoacetate and glucose as lipid precursors and energy substrates in primary cultures of astrocytes and neurons from mouse cerebral cortex. J Neurochem 1986; 46: 773-778
2. Künnecke B, Cerdan S, Seelig J. Cerebral metabolism of [1, 2-13C2]glucose and [U-13C4]3-hydroxybutyrate in rat brain as detected by 13C NMR spectroscopy. NMR Biomed 1993; 6: 264-277
3. Pan JW, de Graaf RA, Petersen KF, Shulman GI, Hetherington HP, Rothman DL. [2, 4-13 C2]b-Hydroxybutyrate metabolism in human brain. J Cereb Blood Flow Metab 2002; 22: 890-898
4. Jiang L, Mason GF, RA Rothman DL, de Graaf RA, Behar KL. Cortical substrate oxidation during hyperketonemia in the fasted anesthetized rat in vivo. J Cereb Blood Flow Metab 2011; 31: 2313-2323
5. Sibson NR, Dhankhar A, Mason GF, Rothman DL, Behar KL, Shulman RG. Stoichiometric coupling of brain glucose metabolism and glutamatergic neuronal activity. Proc Natl Acad Sci USA 1998; 95: 316-321
6. Patel AB, de Graaf RA, Mason GF, Rothman DL, Shulman RG, Behar KL. The contribution of GABA to glutamate/glutamine cycling and energy metabolism in the rat cortex in vivo. Proc Natl Acad Sci USA 2005; 102: 5588-5593
7. Chowdhury GMI, Patel AB, Mason GF, Rothman DL, Behar KL. Glutamatergic and GABAergic neurotransmitter cycling and energy metabolism in rat cerebral cortex during postnatal development. J Cereb Blood Flow Metab 2007; 27: 1895-1907
8. Rothman DL, De Feyter HM, de Graaf RA, Mason GF, Behar KL. 13C MRS studies of neuroenergetics and neurotransmitter cycling in humans. NMR Biomed 2011; 24: 943-957
9. Hyder F, Rothman DL, Bennett MR. Cortical energy demands of signaling and nonsignaling components in brain are conserved across mammalian species and activity levels. Proc Natl Acad Sci USA 2013; 110: 3549-3554
10. Magistretti PJ, Pellerin L, Rothman DL, Shulman RG. Energy on demand. Science 1999; 283: 496-497
11. Chowdhury GMI, Banasr M, de Graaf RA, Rothman DL, Behar KL, Sanacora G. Chronic riluzole treatment increases glucose metabolism in rat prefrontal cortex and hippocampus. J Cereb Blood Flow Metab. 2008; 28: 1892-1897
12. de Graaf RA, Brown PB, Mason GF, Rothman DL, Behar KL. Detection of [1, 6-13C2]-glucose metabolism in rat brain by in vivo 1H-[13C]-NMR spectroscopy. Magn Reson Med 2003; 49: 37-46
13. Chowdhury GMI, Gupta M, Gibson KM, Patel AB, Behar KL. Altered cerebral glucose and acetate metabolism in succinic semialdehyde dehydrogenase-deficient mice: Evidence for glial dysfunction and reduced glutamate/glutamine cycling. J Neurochem 2007; 103: 2077-2091
14. Mason GF, Falk Petersen K, de Graaf RA, Kanamatsu T, Otsuki T, Shulman GI et al. A comparison of 13C NMR measurements of the rates of glutamine synthesis and the tricarboxylic acid cycle during oral and intravenous administration of [1-13C]glucose. Brain Res Brain Res Protoc 2003; 10: 181-190
15. Shen J, Rothman DL, Behar KL, Xu S. Determination of the glutamate-glutamine cycling flux using two-compartment dynamic metabolic modeling is sensitive to astroglial dilution. J Cereb Blood Flow Metab 2009; 29: 108-118
16. Lu DM, Davis DW, Mans AM, Hawkins RA. Regional cerebral glucose utilization measured with [14C]glucose in brief experiments. Am J Physiol 1983; 245(5 Pt 1): C428-C438
17. Choi IY, Lei HX, Gruetter R. Effect of deep pentobarbital anesthesia on neurotransmitter metabolism in vivo: On the correlation of total glucose consumption with glutamatergic action. J Cereb Blood Flow Metab 2002; 22: 1343-1351
18. Cruz NF, Lasater A, Zielke HR, Dienel GA. Activation of astrocytes in brains of conscious rats during acoustic stimulation: Acetate utilization in working brain. J Neurochem 2005; 92: 934-947
19. Edmond J, Auestad N, Robbins RA, Bergstrom JD. Ketone body metabolism in the neonate: Development and the effect of diet. Fed Proc 1985; 44: 2359-2364
20. Cremer JE. Measurement of brain substrate utilization in adult and infant rats using various 14C-labeled precursors. In Passonneau JV, Hawkins RA, Lust WD, Welsh FA (eds). Cerebral Metabolism and Neural Function. Williams and Wilkins: Baltimore, MD, USA, 1982, pp 300-308
21. Miller AL. Regional glucose and b-hydroxybutyrate use by developing rat brain. Metab Brain Dis 1986; 1: 53-61
22. Nehlig A, Boyet S, Pereira de Vasconcelos A. Autoradiographic measurement of local cerebral beta-hydroxybutyrate uptake in the rat during postnatal development. Neurosci 1991; 40: 871-878
23. Nehlig A. Brain uptake and metabolism of ketone bodies in animal models. Prost Leuko. Essen Fatty Acids 2004; 70: 265-275
24. Thio LL, Wong M, Yamada KA. Ketone bodies do not directly alter excitatory or inhibitory hippocampal synaptic transmission. Neurol 2000; 54: 325-331
25. Bak LK, Schousboe A, Sonnewald U, Waagepetersen HS. Glucose is necessary to maintain neurotransmitter homeostasis during synaptic activity in cultured glutamatergic neurons. J Cereb Blood Flow Metab 2006; 26: 1285-1297
26. Lund TM, Risa O, Sonnewald U, Schousboe A, Waagepetersen HS. Availability of neurotransmitter glutamate is diminished when beta-hydroxybutyrate replaces glucose in cultured neurons. J Neurochem 2009; 110: 80-91
27. Hawkins RA, Mans AM, Davis DW. Regional ketone body utilization by rat brain in starvation and diabetes. Am J Physiol 1986; 250(2 Pt 1): E169-E178
28. Hawkins RA, Williamson DH, Krebs HA. Ketone-body utilization by adult and suckling rat brain in vivo. Biochem J 1971; 122: 13-18
29. Dahlquist G, Persson B. The rate of cerebral utilization of glucose, ketone bodies, and oxygen: A comparative in vivo study of infant and adult rats. Pediatr Res 1976; 10: 910-917
30. Ruderman NB, Ross PS, Berger M, Goodman MN. Regulation of glucose and ketonebody metabolism in brain of anaesthetized rats. Biochem J 1974; 138: 1-10
31. Williamson DH, Bates MW, Page MA, Krebs HA. Activities of enzymes involved in acetoacetate utilization in adult mammalian tissues. Biochem J 1971; 121: 41-47
32. Page MA, Krebs HA, Williamson DH. Activities of enzymes of ketone-body utilization in brain and other tissues of suckling rats. Biochem J 1971; 121: 49-53
33. Middleton B. The acetoacetyl-coenzyme A thiolases of rat brain and their relative activities during postnatal development. Biochem J 1973; 132: 731-737
34. Booth RF, Patel TB, Clark JB. The development of enzymes of energy metabolism in the brain of a precocial (guinea pig) and non-precocial (rat) species. J Neurochem 1980; 34: 17-25
35. Nielsen NC, Zahler WL, Fleischer S. Mitochondrial D-b-hydroxybutyrate dehydrogenase. IV. Kinetic analysis of reaction mechanism. J Biol Chem 1973; 248: 2556-2562
36. Dombrowski GJ, Cheung GP, Swiatek KR. Evidence for the existence of enzymatic variants of beta-hydroxybutyrate dehydrogenase from rat liver and brain mitochondria. Life Sci 1977; 21: 1821-1829
37. Owen OE, Morgan AP, Kemp HG, Sullivan JM, Herrera MG, Cahill GF. Brain metabolism during fasting. J Clin Invest 1967; 46: 1589-1595
38. Hertz L, Yu AC, Kala G, Schousboe A. Neuronal-Astrocytic and cytosolicmitochondrial metabolite trafficking during brain activation, hyperammonemia and energy deprivation. Neurochem Int 2000; 37: 83-102
39. Hyder F, Patel AB, Gjedde A, Rothman DL, Behar KL, Shulman RG. NeuronalYglial glucose oxidation and glutamatergic-GABAergic function. J Cereb Blood Flow Metab 2006; 26: 865-877
40. Patel AB, Lai JCK, Chowdhury GMI, Hyder F, Rothman DL, Shulman RG et al. Direct evidence for activity-dependent glucose phosphorylation in neurons with implications for the astrocyte-To-neuron lactate shuttle. Proc Nat Acad Sci USA 2014; 111: 5385-5390