Journal
JOURNAL OF CEREBRAL BLOOD FLOW AND METABOLISM
Volume 34, Issue 7, Pages 1233-1242Publisher
SAGE PUBLICATIONS INC
DOI: 10.1038/jcbfm.2014.77
Keywords
C-13 isotopes; glucose utilization; glutamate/glutamine cycle; ketone body utilization; neuroenergetics; nuclear magnetic resonance spectroscopy
Categories
Funding
- NIH [NIDDK 3R01-DK027121, ARRA R01-DK027121-28S, NIMH R01-MH095104, HINDS R01-NS051854, NINDS 5P30-NS052519]
Ask authors/readers for more resources
The capacity of ketone bodies to replace glucose in support of neuronal function is unresolved. Here, we determined the contributions of glucose and ketone bodies to neocortical oxidative Metabolism over a large range of brain activity in rats fasted 36 hours and infused intravenously with [2,4-C-13(2)]-D-beta-hydroxybutyrate (BHB). Three animal groups and conditions were studied: awake ex vivo, pentobarbital-induced isoelectricity ex vivo, and halothane-anesthetized in vivo, the latter data reanalyzed from a recent study. Rates of neuronal acetyl-CoA oxidation from ketone bodies (VaccoA-kbN) and pyruvate (V-pdhN), and the glutamate-glutamine cycle (V-cyc) were determined by metabolic modeling of C-13 label trapped in major brain amino acid pools. VacCoA-kbN increased gradually with increasing activity, as compared with the steeper change in tricarboxylic acid (TCA) cycle rate (V-tcaN), supporting a decreasing percentage of neuronal ketone oxidation: similar to 100% (isoelectricity), 56% (halothane anesthesia), 36% (awake) with the BHB plasma levels achieved in our experiments (6 to 13 mM). In awake animals ketone oxidation reached saturation for blood levels > 17 mM, accounting for 62% of neuronal substrate oxidation, the remainder (38 /o) provided by glucose. We conclude that ketone bodies present at sufficient concentration to saturate metabolism provides full support of basal (housekeeping) energy needs and up to approximately half Of the activity-dependent oxidative needs of neurons.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available