Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate
J Cereb Blood Flow Metab. 2016-07-22; 36(10): 1813-1822
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Valdebenito R(1), Ruminot I(2), Garrido-Gerter P(3), Fernández-Moncada I(3),
Forero-Quintero L(2), Alegría K(1), Becker HM(2), Deitmer JW(2), Barros LF(4).
(1)Centro de Estudios Científicos, Valdivia, Chile.
(2)General Zoology/University of Kaiserslautern, Kaiserslautern, Germany.
(3)Centro de Estudios Científicos, Valdivia, Chile Universidad Austral de Chile,
(4)Centro de Estudios Científicos, Valdivia, Chile .
The effectiveness of ketogenic diets and intermittent fasting against
neurological disorders has brought interest to the effects of ketone bodies on
brain cells. These compounds are known to modify the metabolism of neurons, but
little is known about their effect on astrocytes, cells that control the supply
of glucose to neurons and also modulate neuronal excitability through the
glycolytic production of lactate. Here we have used genetically-encoded Förster
Resonance Energy Transfer nanosensors for glucose, pyruvate and ATP to
characterize astrocytic energy metabolism at cellular resolution. Our results
show that the ketone body beta-hydroxybutyrate strongly inhibited astrocytic
glucose consumption in mouse astrocytes in mixed cultures, in organotypic
hippocampal slices and in acute hippocampal slices prepared from ketotic mice,
while blunting the stimulation of glycolysis by physiological and
pathophysiological stimuli. The inhibition of glycolysis was paralleled by an
increased ability of astrocytic mitochondria to metabolize pyruvate. These
results support the emerging notion that astrocytes contribute to the
neuroprotective effect of ketone bodies.