Ketone body synthesis in the brain: possible neuroprotective effects

Abstract

Ketone bodies make an important contribution to brain energy production and biosynthetic processes when glucose becomes scarce. Although it is generally assumed that the liver supplies the brain with ketone bodies, recent evidence shows that cultured astrocytes are also ketogenic cells. Moreover, astrocyte ketogenesis might participate in the control of the survival/death decision of neural cells in at least two manners: first, by scavenging non-esterified fatty acids the ketogenic pathway would prevent the detrimental actions of these compounds and their derivatives (e.g. ceramide) on brain structure and function. Second, ketone bodies may exert pro-survival actions per se by acting as cellular substrates, thereby preserving neuronal synaptic function and structural stability. These findings support the notion that ketone bodies produced by astrocytes may be used in situ as substrates for neuronal metabolism, and raise the possibility that astrocyte ketogenesis is a neuroprotective pathway.