Abstract
The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as β-hydroxybutyrate (βHB) and acetoacetate (AcAc), as occurs with fasting, prolonged starvation or chronic feeding of a high fat/low carbohydrate diet (ketogenic diet). In this study, the local cerebral metabolic rate of glucose consumption (CMRglu; μM/min/100g) was calculated in the cortex and cerebellum of control and ketotic rats using Patlak analysis. Rats were imaged on a rodent PET scanner and MRI was performed on a 7-Tesla Bruker scanner for registration with the PET images. Plasma glucose and βHB concentrations were measured and 90-minute dynamic PET scans were started simultaneously with bolus injection of 2-Deoxy-2[18F]Fluoro-D-Glucose (FDG).The blood radioactivity concentration was automatically sampled from the tail vein for 3 min following injection and manual periodic blood samples were taken. The calculated local CMRGlu decreased with increasing plasma BHB concentration in the cerebellum (CMRGlu = -4.07*[BHB] + 61.4, r² = 0.3) and in the frontal cortex (CMRGlu = - 3.93*[BHB] + 42.7, r² = 0.5). These data indicate that, under conditions of ketosis, glucose consumption is decreased in the cortex and cerebellum by about 10% per each mM of plasma ketone bodies.
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Keywords
- Positron Emission Tomography
- Cerebral Blood Flow
- Positron Emission Tomography Image
- Glucose Consumption
- Ketone Body
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References
R. A. Hawkins and J.F. Biebuyck: Ketone bodies are selectively used by individual brain regions. Science 205:325-327 (1979).
S. G. Hasselbalch, P.L. Madsen, L.P. Hageman, K.S. Olsen, N. Justesen, S. Holm, and O.B. Paulson: Changes in cerebral blood flow and carbohydrate metabolism during acute hyperketonemia. Am J Physiol 270:E746-E751(1996).
E. O. Balasse and F. Fery: Ketone body production and disposal: effects of fasting, diabetes, and exercise. Diabetes Metab Rev.5:247-270 (1989).
D. H. Corddry, S.I. Rapoport, and E.D. London: No effect of hyperketonemia on local cerebral glucose utilization in conscious rats. J Neurochem.38:1637-1641 (1982).
N. B. Ruderman, P.S. Ross, M. Berger, and M.N. Goodman: Regulation of glucose and ketone-body metabolism in brain of anaesthetized rats. Biochem.J138:1-10 (1974).
O. E. Owen, A.P. Morgan, H.G. Kemp, J.M. Sullivan, M.G. Herrera, and G.F.jr. Cahill: Brain metabolism during fasting. J.Clin.Invest.46:1589-1595 (1967).
G. Dahlquist and B. Persson: The rate of cerebral utilization of glucose, ketone bodies, and oxygen: a comparative in vivo study of infant and adult rats. Pediatr.Res10:910-917 (1976).
A. S. al Mudallal, B.E. Levin, W.D. Lust, and S.I. Harik: Effects of unbalanced diets on cerebral glucose metabolism in the adult rat. Neurol.45:2261-2265 (1995).
A. S. Al-Mudallal, J.C. LaManna, W.D. Lust, and S.I. Harik: Diet-induced ketosis does not cause cerebral acidosis. Epilepsia37:258-261 (1996).
M. A. Puchowicz, K. Xu, X. Sun, A. Ivy, D. Emancipator, and J.C. LaManna: Diet-induced ketosis increases capillary density without altered blood flow in rat brain. Am J Physiol Endocrinol.Metab (2007).
V. Lebon, K.F. Petersen, G.W. Cline, J. Shen, G.F. Mason, S. Dufour, K.L. Behar, G.I. Shulman, and D.L. Rothman: 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. {\it J Neurosci. 22:1523-1531 (2002).
I. Tkac, Z. Starcuk, I.Y. Choi, and R. Gruetter: In vivo 1H NMR spectroscopy of rat brain at 1 ms echo time. Magn Reson.Med.41:649-656 (1999).
R. A. Hawkins, A.W. Mans, and D.W. Davis: Regional ketone body utilization by rat brain in starvation and diabetes. Am.J.Physiol.250:E169-E178(1986).
M. A. Puchowicz, D.S. Emancipator, K. Xu, D.L. Magness, O.I. Ndubuizu, W.D. Lust, and J.C. LaManna: Adaptation to chronic hypoxia during diet-induced ketosis. Adv.Exp.Med.Biol.566:51-57 (2005).
R. L. Veech: The therapeutic implications of ketone bodies: the effects of ketone bodies in pathological conditions: ketosis, ketogenic diet, redox states, insulin resistance, and mitochondrial metabolism. Prostaglandins Leukot.Essent.Fatty Acids70:309-319 (2004).
A. S. Y. Chang and L.G. D’Alecy: Hypoxia and beta-hydroxybutyrate acutely reduce glucose extraction by the brain in anesthetized dogs. Can.J.Physiol.Pharmacol.71:465-472 (1993).
R. Masuda, J.W. Monahan, and Y. Kashiwaya: D-beta-hydroxybutyrate is neuroprotective against hypoxia in serum-free hippocampal primary cultures. J Neurosci.Res80:501-509 (2005).
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LaManna, J.C. et al. (2009). Ketones Suppress Brain Glucose Consumption. In: Liss, P., Hansell, P., Bruley, D.F., Harrison, D.K. (eds) Oxygen Transport to Tissue XXX. Advances in Experimental Medicine and Biology, vol 645. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-85998-9_45
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DOI: https://doi.org/10.1007/978-0-387-85998-9_45
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