Acetate supplementation attenuates lipopolysaccharide‐induced neuroinflammation

J. Neurochem. (2011) 117, 264–274. Glyceryl triacetate (GTA), a compound effective at increasing circulating and tissue levels of acetate was used to treat rats subjected to a continual 28 day intra‐ventricular infusion of bacterial lipopolysaccharide (LPS). This model produces a neuroinflammatory injury characterized by global neuroglial activation and a decrease in choline acetyltransferase immunoreactivity in the basal forebrain. During the LPS infusion, rats were given a daily treatment of either water or GTA at a dose of 6 g/kg by oral gavage. In parallel experiments, free‐CoA and acetyl‐CoA levels were measured in microwave fixed brains and flash frozen heart, liver, kidney and muscle following a single oral dose of GTA. We found that a single oral dose of GTA significantly increased plasma acetate levels by 15 min and remained elevated for up to 4 h. At 30 min the acetyl‐CoA levels in microwave‐fixed brain and flash frozen heart and liver were increased at least 2.2‐fold. The concentrations of brain acetyl‐CoA was significantly increased between 30 and 45 min following treatment and remained elevated for up to 4 h. The concentration of free‐CoA in brain was significantly decreased compared to controls at 240 min. Immunohistochemical and morphological analysis demonstrated that a daily treatment with GTA significantly reduced the percentage of reactive glial fibrillary acidic protein‐positive astrocytes and activated CD11b‐positive microglia by 40–50% in rats subjected to LPS‐induced neuroinflammation. Further, in rats subjected to neuroinflammation, GTA significantly increased the number of choline acetyltransferase (ChAT)‐positive cells by 40% in the basal forebrain compared to untreated controls. These data suggest that acetate supplementation increases intermediary short chain acetyl‐CoA metabolism and that treatment is potentially anti‐inflammatory and neuroprotective with regards to attenuating neuroglial activation and increasing ChAT immunoreactivity in this model.