Increased brain uptake and oxidation of acetate in heavy drinkers

Journal of Clinical Investigation

Volumn 123, Issue 4, 2013, Pages 1605-1614

  Jiang, Lihong ^a   Gulanski, Barbara Irene ^a   De Feyter, Henk M ^a   Weinzimer, Stuart A ^a   Pittman, Brian ^a   Guidone, Elizabeth ^a   Koretski, Julia ^a   Harman, Susan ^a   Petrakis, Ismene L ^a   Krystal, John H ^a   Mason, Graeme F ^a  

^a YALE UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ACETIC ACID; CARBON 13; GLUTAMIC ACID; GLUTAMINE; N ACETYLASPARTIC ACID;

ADULT; ALCOHOL CONSUMPTION; ARTICLE; BRAIN METABOLISM; CARBON NUCLEAR MAGNETIC RESONANCE; CLINICAL ARTICLE; FEMALE; HUMAN; MALE; METABOLIC RATE; OXIDATION; PRIORITY JOURNAL; STEADY STATE;

ACETATES; ADULT; ALCOHOLISM; BLOOD GLUCOSE; BRAIN; CASE-CONTROL STUDIES; FEMALE; GLUTAMIC ACID; GLUTAMINE; HUMANS; KINETICS; MALE; METABOLIC NETWORKS AND PATHWAYS; MIDDLE AGED; MODELS, BIOLOGICAL; OXIDATION-REDUCTION; YOUNG ADULT;

EID: 84875835696     PISSN: 00219738     EISSN: 15588238     Source Type: Journal    
DOI: 10.1172/JCI65153     Document Type: Article

References (78)

1. Prosser RA, Mangrum CA, Glass JD. Acute ethanol modulates glutamatergic and serotonergic phase shifts of the mouse circadian clock in vitro. Neuroscience. 2008;152(3):837-848.
2. Wallner M, Hanchar HJ, Olsen RW. Low-dose alcohol actions on alpha4beta3delta GABAA receptors are reversed by the behavioral alcohol antagonist Ro15-4513. Proc Natl Acad Sci U S A. 2006;103(22):8540-8545.
3. Wakita M, Shin MC, Iwata S, Nonaka K, Akaike N. Effects of ethanol on GABAA receptors in GABAergic and glutamatergic presynaptic nerve terminals. J Pharmacol Exp Ther. 2012;341(3):809-819.
4. Ting JW, Lautt WW. The effect of acute, chronic, and prenatal ethanol exposure on insulin sensitivity. Pharmacol Ther. 2006;111(2):346-373.
5. Manzo-Avalos S, Saavedra-Molina A. Cellular and mitochondrial effects of alcohol consumption. Int J Environ Res Public Health. 2010;7(12):4281-4304.
6. Lundquist F, Winkler K, Munckpet S, Tygstrup N, Mellemgaard K. Ethanol metabolism and production of free acetate in the human liver. J Clin Invest. 1962;41:955-961.
7. Norberg A, Jones AW, Hahn RG, Gabrielsson JL. Role of variability in explaining ethanol pharmacokinetics-Research and forensic applications. Clinical Pharmacokinetics. 2003;42(1):1-31.
8. Jucker BM, Lee JY, Shulman RG. In vivo C-13 NMR measurements of hepatocellular tricarboxylic acid cycle flux. J Biol Chem. 1998; 273(20):12187-12194.
9. Lundquist F, Sestoft L, Damgaard SE, Clausen JP, Trap-Jensen J. Utilization of acetate in the human forearm during exercise after ethanol ingestion. J Clin Invest. 1973;52(12):3231-3235.
10. Davin A, Vion-Dury J, Viout P, Cozzone PJ. Rapid evaluation of ethanol content and metabolism in human plasma using quantitative proton magnetic resonance spectroscopy. Alcohol Alcohol. 1994;29(5):479-483.
11. Peng G-S, Chen Y-C, Tsao T-P, Wang M-F, Yin S-J. Pharmacokinetic and pharmacodynamic basis for partial protection against alcoholism in Asians, heterozygous for the variant ALDH2*2 gene allele. Pharmacogenet Genomics. 2007;17(10):845-855.
12. Nuutinen H, Lindros K, Hekali P, Salaspuro M. Elevated blood acetate as indicator of fast ethanol elimination in chronic alcoholics. Alcohol. 1985;2(4):623-626.
13. Mascord D, Smith J, Starmer GA, Whitfield JB. Effects of increasing the rate of alcohol metabolism on plasma acetate concentration. Alcohol Alcohol. 1992;27(1):25-28.
14. Patel AB, de Graaf RA, Rothman DL, Behar KL, Mason GF. Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using 1H-[13C]-NMR. J Cereb Blood Flow Metab. 2010;30(6):1200-1213.
15. Hellman L, Rosenfeld RS, Gallagher TF. Cholesterol synthesis from C-14-acetate in man. J Clin Invest. 1954;33(2):142-149.
16. Natali F, Siculella L, Salvati S, Gnoni GV. Oleic acid is a potent inhibitor of fatty acid and cholesterol synthesis in C6 glioma cells. J Lipid Res. 2007;48(9):1966-1975.
17. Pronko PS, Velichko MG, Moroz AR, Rubanovich NN. Low-molecular-weight metabolites relevant to ethanol metabolism: Correlation with alcohol withdrawal severity and utility for identification of alcoholics. Alcohol Alcohol. 1997;32(6):761-768.
18. Kiviluoma KT, Peuhkurinen KJ, Hassinen IE. Adenine nucleotide transport and adenosine production in isolated rat heart mitochondria during acetate metabolism. Biochim Biophys Acta. 1989;974(3):274-281.
19. Kiselevski Y, et al. Acetate metabolism in brain mechanisms of adaptation to ethanol. Med Sci Monit. 2003;9(5):178-182.
20. Mailliard WS, Diamond I. Recent advances in the neurobiology of alcoholism: The role of adenosine. Pharmacol Ther. 2004;101(1):39-46.
21. Diamond I, Nagy L, Mochly-Rosen D, Gordon A. The role of adenosine and adenosine transport in ethanol-induced cellular tolerance and dependence. Possible biologic and genetic markers of alcoholism. Ann N Y Acad Sci. 1991;625:473-487.
22. Carmichael FJ, et al. Central nervous system effects of acetate: Contribution to the central effects of ethanol. J Pharmacol Exp Ther. 1991;259(1):403-408.
23. Carmichael FJ, Orrego H, Saldivia V, Israel Y. Effect of propylthiouracil on the ethanol-induced increase in liver oxygen consumption in awake rats. Hepatology. 1993;18(2):415-421.
24. Carmichael FJ, Orrego H, Israel Y. Acetate-induced adenosine mediated effects of ethanol. Alcohol Alcohol Suppl. 1993;2:411-418.
25. Muir D, Berl S, Clarke DD. Acetate and fluoroacetate as possible markers for glial metabolism in vivo. Brain Res. 1986;380(2):336-340.
26. Jain H, Beriwal S, Singh S. Alcohol induced ketoacidosis, severe hypoglycemia and irreversible encephalopathy. Med Sci Monit. 2002;8(11):CS77-CS79.
27. Jiang L, et al. Recurrent antecedent hypoglycemia alters neuronal oxidative metabolism in vivo. Diabetes. 2009;58(6):1266-1274.
28. Mason GF, Petersen KF, Lebon V, Rothman DL, Shulman GI. Increased brain monocarboxylic acid transport and utilization in type 1 diabetes. Diabetes. 2006;55(4):929-934.
29. Volkow ND, et al. Low doses of alcohol substantially decrease glucose metabolism in the human brain. Neuroimage. 2006;29(1):295-301.
30. Volkow ND, et al. Acute alcohol intoxication decreases glucose metabolism but increases acetate uptake in the human brain. Neuroimage. 2013;64:277-283.
31. Pawlosky RJ, et al. Alterations in brain glucose utilization accompanying elevations in blood ethanol and acetate concentrations in the rat. Alcohol Clin Exp Res. 2010;34(2):375-381.
32. Sarkola T, Iles MR, Kohlenberg-Mueller K, Eriksson CJ. Ethanol, acetaldehyde, acetate, and lactate levels after alcohol intake in white men and women: Effect of 4-methylpyrazole. Alcohol Clin Exp Res. 2002;26(2):239-245.
33. Clubb R, Mason G. Animal welfare: Captivity effects on wide-ranging carnivores. Nature. 2003;425(6957):473-474.
34. Lebon V, et al. Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: Elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci. 2002;22(5):1523-1531.
35. Brusilow SW, Koehler RC, Traystman RJ, Cooper AJL. Astrocyte glutamine synthetase: Importance in hyperammonemic syndromes and potential target for therapy. Neurotherapeutics. 2010;7(4):452-470.
36. Shulman RG, Rothman DL, Behar KL, Hyder F. Energetic basis of brain activity: Implications for neuroimaging. Trends Neurosci. 2004;27(8):489-495.
37. Volkow N, et al. Decreased brain metabolism in neurologically intact healthy alcoholics. Am J Psychiatry. 1992;149(8):1016-1022.
38. Hommer D, et al. Effects of m-chlorophenylpiperazine on regional brain glucose utilization: A positron emission tomographic comparison of alcoholic and control subjects. J Neurosci. 1997;17(8):2796-2806.
39. Theberge J, et al. Glutamate and glutamine measured with 4.0 T proton MRS in never-treated patients with schizophrenia and healthy volunteers. Am J Psychiatry. 2002;159(11):1944-1946.
40. Korri UM, Nuutinen H, Salaspuro M. Increased blood acetate: A new laboratory marker of alcoholism and heavy drinking. Alcohol Clin Exp Res. 1985;9(5):468-471.
41. McBride WJ, Li TK. Animal models of alcoholism: Neurobiology of high alcohol-drinking behavior in rodents. Crit Rev Neurobiol. 1998;12(4):339-369.
42. Marks V. Clinical pathology of alcohol. J Clin Pathol. 1983;36(4):365-378.
43. Patel AB, De Graaf RA, Rothman DL, Behar KL, Mason GF. Evaluation of cerebral acetate transport and metabolic rates in the rat brain in vivo using (1)H-(13)C-NMR. J Cereb Blood Flow Metab. 2010;30(6):1200-1213.
44. Brecher AS, Lehti MD. A hypothesis linking hypoglycemia, hyperuricemia, lactic acidemia, and reduced gluconeogenesis in alcoholics to inactivation of glucose-6-phosphatase activity by acetaldehyde. Alcohol. 1996;13(6):553-557.
45. Krebs HA, Freedland RA, Hems R, Stubbs M. Inhibition of hepatic gluconeogenesis by ethanol. Biochem J. 1969;112(1):117-124.
46. Wright J. Endocrine effects of alcohol. Clin Endocrinol Metab. 1978;7(2):351-367.
47. Juhlin-Dannfelt A. Ethanol effects of substrate utilization by the human brain. Scand J Clin Lab Invest. 1977;37(5):443-449.
48. Sporer KA, Ernst AA, Conte R, Nick TG. The incidence of ethanol-induced hypoglycemia. Am J Emerg Med. 1992;10(5):403-405.
49. Waniewski RA, Martin DL. Astrocytes and synaptosomes transport and metabolize lactate and acetate differently. Neurochem Res. 2004;29(1):209-217.
50. Borowiec A, Lechward K, Tkacz-Stachowska K, Skladanowski AC. Adenosine as a metabolic regulator of tissue function: Production of adenosine by cytoplasmic 5'-nucleotidases. Acta Biochim Pol. 2006;53(2):269-278.
51. Dunwiddie TV, Diao L, Proctor WR. Adenine nucleotides undergo rapid, quantitative conversion to adenosine in the extracellular space in rat hippocampus. J Neurosci. 1997;17(20):7673-7682.
52. Kiviluoma KT, Peuhkurinen KJ, Hassinen IE. Adenine nucleotide transport and adenosine production in isolated rat heart mitochondria during acetate metabolism. Biochim Biophys Acta. 1989;974(3):274-281.
53. Verdy M, Saliou-Diallo G. [Hypoglycemia and alcohol]. Can Med Assoc J. 1968;98(17):827-830.
54. Asatryan L, et al. Implication of the purinergic system in alcohol use disorders. Alcohol Clin Exp Res. 2011;35(4):584-594.
55. Badar-Goffer RS, Bachelard HS, Morris PG. Cerebral metabolism of acetate and glucose studied by 13C-n.m.r. spectroscopy. A technique for investigating metabolic compartmentation in the brain. Biochem J. 1990;266(1):133-139.
56. Lebon V, et al. Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: Elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci. 2002;22(5):1523-1531.
57. van den Berg CJ, Garfinkel D. A stimulation study of brain compartments. Metabolism of glutamate and related substances in mouse brain. Biochem J. 1971;123(2):211-218.
58. 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 U S A. 2005;102(15):5588-5593.
59. Feinstein A, Stergiopoulos V, Fine J, Lang AE. Psychiatric outcome in patients with a psychogenic movement disorder: A prospective study. Neuropsychiatry Neuropsychol Behav Neurol. 2001;14(3):169-176.
60. Sobell LC, Sobell MB. Timeline follow-back: A technique for assessing self-reported alcohol consumption. In: Litten RZ, Allen JP, eds. Measuring Alcohol Consumption: Psychosocial And Biochemical Methods. Totowa, New Jersey, USA: Humana Press; 1993:41-72.
61. Coles L, Litt J, Hatta H, Bonen A. Exercise rapidly increases expression of the monocarboxylate transporters MCT1 and MCT4 in rat muscle. J Physiol. 2004;561(pt 1):253-261.
62. Leino RL, Gerhart DZ, Duelli R, Enerson BE, Drewes LR. Diet-induced ketosis increases monocarboxylate transporter (MCT1) levels in rat brain. Neurochem Int. 2001;38(6):519-527.
63. Morgan P, et al. Cortical GABA levels in primary insomnia. Sleep. 2012;35(6):807-814.
64. Shen J, Rycyna RE, Rothman DL. Improvements on an in vivo automatic shimming method [FASTERMAP]. Magn Reson Med. 1997;38(5):834-839.
65. Rothman DL, Petroff OA, Behar KL, Mattson RH. Localized 1H NMR measurements of gamma-aminobutyric acid in human brain in vivo. Proc Natl Acad Sci U S A. 1993;90(12):5662-5666.
66. Boumezbeur F, et al. Altered brain mitochondrial metabolism in healthy aging as assessed by in vivo magnetic resonance spectroscopy. J Cereb Blood Flow Metab. 2010;30(1):211-221.
67. Shen J, et al. Determination of the rate of the glutamate/glutamine cycle in the human brain by in vivo 13C NMR. Proc Natl Acad Sci U S A. 1999; 96(14):8235-8240.
68. Shen J, Rycyna RE, Rothman DL. Improvements on an in vivo automatic shimming method [FASTERMAP]. Magn Reson Med. 1997;38(5):834-839.
69. Valentine GW, et al. The antidepressant effect of ketamine is not associated with changes in occipital amino acid neurotransmitter content as measured by [(1)H]-MRS. Psychiatry Res. 2011;191(2):122-127.
70. Mason GF, Rothman DL, Behar KL, Shulman RG. NMR determination of the TCA cycle rate and alpha-ketoglutarate/glutamate exchange rate in rat brain. J Cereb Blood Flow Metab. 1992;12(3):434-447.
71. 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 U S A. 2005;102(15):5588-5593.
72. Gjedde A, Diemer NH. Autoradiographic determination of regional brain glucose content. J Cereb Blood Flow Metab. 1983;3(3):303-310.
73. Gruetter R, Ugurbil K, Seaquist ER. Steady-state cerebral glucose concentrations and transport in the human brain. J Neurochem. 1998;70(1):397-408.
74. Mason GF, Petersen KF, de Graaf RA, Shulman GI, Rothman DL. Measurements of the anaplerotic rate in the human cerebral cortex using 13C magnetic resonance spectroscopy and [1-13C] and [2-13C] glucose. J Neurochem. 2007;100(1):73-86.
75. Mason GF, Gruetter R, Rothman DL, Behar KL, Shulman RG, Novotny EJ. Simultaneous determination of the rates of the TCA cycle, glucose utilization, alpha-ketoglutarate/glutamate exchange, and glutamine synthesis in human brain by NMR. J Cereb Blood Flow Metab. 1995;15(1):12-25.
76. Gruetter R, Seaquist ER, Ugurbil K. A mathematical model of compartmentalized neurotransmitter metabolism in the human brain. Am J Physiol Endocrinol Metab. 2001;281(1):E100-E112.
77. Gruetter R, et al. Localized 13C NMR spectroscopy in the human brain of amino acid labeling from D-[1-13C]glucose. J Neurochem. 1994;63(4):1377-1385.
78. Lebon V, et al. Astroglial contribution to brain energy metabolism in humans revealed by 13C nuclear magnetic resonance spectroscopy: Elucidation of the dominant pathway for neurotransmitter glutamate repletion and measurement of astrocytic oxidative metabolism. J Neurosci. 2002;22(5):1523-1531.