Acetate is primarily produced in the liver during alcohol metabolism (Figure 3), but is also generated within the brain. Systemic concentrations of acetate are around 0.2 mM, but increase to 0.5 – 1.0 mM following alcohol intake. When acetate enters the tricarboxylic acid (TCA) cycle, it can be oxidized to generate adenosine, a neuromodulator that, like alcohol, has central depressant effects (140). After alcohol consumption, astrocytes preferentially use acetate as an alternative fuel to glucose (146). Clinical neuroimaging studies indicate that both acute and chronic heavy alcohol drinking increase cerebral acetate uptake and lower brain glucose metabolism (147, 148), with the cerebellum showing the greatest shift toward acetate use (reviewed in (149)).
