Ketosis Proportionately Spares Glucose Utilization in Brain

Abstract

The brain is dependent on glucose as a primary energy substrate, but is capable of utilizing ketones such as b-hydroxybutyrate and acetoacetate, as occurs with fasting, starvation, or chronic feeding of a ketogenic diet. The relationship between changes in cerebral metabolic rates of glucose (CMR glc ) and degree or duration of ketosis remains uncertain. To investigate if CMR glc decreases with chronic ketosis, 2-[18 F]fluoro-2-deoxy-D-glucose in combination with positron emission tomography, was applied in anesthetized young adult rats fed 3 weeks of either standard or ketogenic diets. Cerebral metabolic rates of glucose (mmol/min per 100 g) was determined in the cerebral cortex and cerebellum using Gjedde-Patlak analysis. The average CMR glc significantly decreased in the cerebral cortex (23.0 ± 4.9 versus 32.9 ± 4.7) and cerebellum (29.3 ± 8.6 versus 41.2 ± 6.4) with increased plasma ketone bodies in the ketotic rats compared with standard diet group. The reduction of CMR glc in both brain regions correlates linearly by B9% for each 1 mmol/L increase of total plasma ketone bodies (0.3 to 6.3 mmol/L). Together with our meta-analysis, these data revealed that the degree and duration of ketosis has a major role in determining the corresponding change in CMR glc with ketosis.

Protection of Hypoglycemia-Induced Neuronal Death by β-Hydroxybutyrate Involves the Preservation of Energy Levels and Decreased Production of Reactive Oxygen Species

“…These results agree with recent reports suggesting that D-BHB can be used as an alternative substrate, as a decrease in the glucose metabolic rate is observed in the brain of animals subjected to the ketogenic diet. 31,32 In vitro data show that D-BHB notably prevents neuronal death when incubated during GD and GR, but is also effective when incubated only during GD or only during GR. Consistently, ATP levels recover to the same extent when D-BHB is present only during GD, only during GR or during both periods.…”

Rapid Adaptation of Rat Brain and Liver Metabolism to a Ketogenic Diet: An Integrated Study Using 1H- and 13C-NMR Spectroscopy

“…[1][2][3][4][5][6][7][8][9][10][11][12][13] C]Glc (D-glucose) or [2,4-13 C 2 ]β-HB (sodium D-3-hydroxybutyrate) (Cambridge Isotope Laboratories, Andover, MA, USA) was then infused into the tail vein over a total period of 60 minutes. The [1-13 C]Glc infusion followed our previous 20 steps, time-decreasing exponential rate protocol, going from 15 to 1.23 mL/h during the first 25 minutes, after which the rate was kept unchanged for the last 35 minutes.…”

“…15 Total Glc administered was 2.19 mmol/h per 200 g body weight. [2,[4][5][6][7][8][9][10][11][12][13] C 2 ]β-HB was infused according to a three-step protocol: 9 (1) 0 to 5 minutes at 80 μL/min per 200 g body weight, (2) 5 to 10 minutes at 40 μL/min per 200 g body weight, and (3) 10 to 60 minutes at 16 μL/min per 200 g body weight. Total β-HB infused was 2.1 mmol/h per 200 g body weight (stock solution concentration = 1.5 mol/L).…”

“…8 It is of interest to know the impact of the KD on brain fuel utilization. Some studies report that the KD decreases brain Glc uptake 9,10 while others have shown that it increases brain Glc transporter expression 11 or 18 F-fluorodeoxyglucose uptake using positron emission tomography. 5,12 The primary aim of the present study was to investigate the short-term effects of the KD on brain metabolism, using mainly 13 C-NMR spectroscopy, a technique that allows the study of metabolic pathways by following the fate of 13 C-labeled substrates.…”

“…Tail vein whole blood β-HB was measured every other day using test strips and a hand-held device (Precision Xtra, Abbott Laboratories, Alameda, CA, USA). At the end of the 7-day feeding period, the CT and KD groups were each separated into two subgroups for the substrate infusion: [1][2][3][4][5][6][7][8][9][10][11][12][13] C]Glc or [2,[4][5][6][7][8][9][10][11][12][13] C 2 ]β-HB (n = 6/subgroup). The experimental protocol was approved by the Institutional Animal Research Ethics Review Board and met the guidelines of the French governmental agency (In accordance with ARRIVE: personal authorization no.…”