Acetate transport and utilization in the rat brain

• Published in: Journal of neurochemistry 2009-05, Vol.109 (s1), p.46-54
• Main Authors: Deelchand, Dinesh K, Shestov, Alexander A, Koski, Dee M, Uğurbil, Kâmil, Henry, Pierre-Gilles
• Format: Article
• Language: English
• Subjects: 13C; acetate; Acetates - administration & dosage; Acetates - blood; Acetates - metabolism; Algorithms; Amino Acids - metabolism; Animals; Astrocytes - metabolism; Biochemistry; Biological Transport, Active - physiology; Biotransformation; Brain; Brain Chemistry - physiology; C; Citric Acid Cycle - physiology; Glutamic Acid - metabolism; Glutamine - metabolism; Infusions, Intravenous; Kinetics; LCModel; Magnetic Resonance Spectroscopy; Male; Neurology; NMR spectroscopy; nuclear magnetic resonance spectroscopy; Pyruvate Carboxylase - metabolism; Rats; Rats, Sprague-Dawley; Rodents; Substrates; transport
• ISSN: 0022-3042; 1471-4159
• DOI: 10.1111/j.1471-4159.2009.05895.x

Acetate, a glial-specific substrate, is an attractive alternative to glucose for the study of neuronal-glial interactions. The present study investigates the kinetics of acetate uptake and utilization in the rat brain in vivo during infusion of [2-¹³C]acetate using NMR spectroscopy. When plasma acetate concentration was increased, the rate of brain acetate utilization (CMRace) increased progressively and reached close to saturation for plasma acetate concentration > 2-3 mM, whereas brain acetate concentration continued to increase. The Michaelis-Menten constant for brain acetate utilization ( [graphic removed] = 0.01 ± 0.14 mM) was much smaller than for acetate transport through the blood-brain barrier (BBB) ( [graphic removed] = 4.18 ± 0.83 mM). The maximum transport capacity of acetate through the BBB ( [graphic removed] = 0.96 ± 0.18 μmol/g/min) was nearly twofold higher than the maximum rate of brain acetate utilization ( [graphic removed] = 0.50 ± 0.08 μmol/g/min). We conclude that, under our experimental conditions, brain acetate utilization is saturated when plasma acetate concentrations increase above 2-3 mM. At such high plasma acetate concentration, the rate-limiting step for glial acetate metabolism is not the BBB, but occurs after entry of acetate into the brain.