title: Targeting of astrocytic glucose metabolism by beta-hydroxybutyrate.
abstract: 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.
authors.affiliation: Centro de Estudios Científicos, Valdivia, Chile.
authors.forename: Rocío
authors.initials: R
authors.lastname: Valdebenito
authors.affiliation: General Zoology/University of Kaiserslautern, Kaiserslautern, Germany.
authors.forename: Iván
authors.initials: I
authors.lastname: Ruminot
authors.affiliation: Centro de Estudios Científicos, Valdivia, Chile Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Pamela
authors.initials: P
authors.lastname: Garrido-Gerter
authors.affiliation: Centro de Estudios Científicos, Valdivia, Chile Universidad Austral de Chile, Valdivia, Chile.
authors.forename: Ignacio
authors.initials: I
authors.lastname: Fernández-Moncada
authors.affiliation: General Zoology/University of Kaiserslautern, Kaiserslautern, Germany.
authors.forename: Linda
authors.initials: L
authors.lastname: Forero-Quintero
authors.affiliation: Centro de Estudios Científicos, Valdivia, Chile.
authors.forename: Karin
authors.initials: K
authors.lastname: Alegría
authors.affiliation: General Zoology/University of Kaiserslautern, Kaiserslautern, Germany.
authors.forename: Holger M
authors.initials: HM
authors.lastname: Becker
authors.affiliation: General Zoology/University of Kaiserslautern, Kaiserslautern, Germany.
authors.forename: Joachim W
authors.initials: JW
authors.lastname: Deitmer
authors.affiliation: Centro de Estudios Científicos, Valdivia, Chile fbarros@cecs.cl.
authors.forename: L Felipe
authors.initials: LF
authors.lastname: Barros
mesh_terms: D020155:3-Hydroxybutyric Acid / Q000494:pharmacology*; D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism; D015374:Biosensing Techniques; D018929:Cell Culture Techniques; D004734:Energy Metabolism; D005260:Female; D031541:Fluorescence Resonance Energy Transfer; D005947:Glucose / Q000378:metabolism*; D006624:Hippocampus / Q000187:drug effects* / Q000378:metabolism; D066298:In Vitro Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008808:Mice, Inbred CBA; D008856:Microscopy, Fluorescence
chemical_list: D005947:Glucose; D020155:3-Hydroxybutyric Acid
keywords: ATeam; FLII12Pglu700µΔ6; Förster Resonance Energy Transfer microscopy; ketone bodies; pyronic