Acetate supplementation attenuates lipopolysaccharide-induced neuroinflammation

Area of Science:

• Neuroscience
• Biochemistry
• Pharmacology

Background:

• Neuroinflammation, induced by bacterial lipopolysaccharide (LPS), causes glial activation and reduced choline acetyltransferase (ChAT) in the basal forebrain.
• Glyceryl triacetate (GTA) increases acetate levels, a key metabolite in cellular energy pathways.

Purpose of the Study:

• To investigate the neuroprotective and anti-inflammatory effects of GTA in an LPS-induced neuroinflammation rat model.
• To assess the impact of GTA on acetyl-CoA metabolism and ChAT immunoreactivity.

Main Methods:

• Rats received continuous intra-ventricular LPS infusion for 28 days, with daily oral gavage of water or GTA (6 g/kg).
• Acetyl-CoA and free-CoA levels were measured in brain and peripheral tissues after a single GTA dose.
• Immunohistochemistry was used to quantify glial markers (GFAP, CD11b) and ChAT-positive cells.

Main Results:

• A single GTA dose increased plasma acetate for 4 hours and elevated brain, heart, and liver acetyl-CoA levels.
• GTA treatment significantly reduced reactive astrocytes and microglia by 40-50% in LPS-infused rats.
• Daily GTA administration increased ChAT-positive cells in the basal forebrain by 40%.

Conclusions:

• Acetate supplementation via GTA enhances short-chain acetyl-CoA metabolism.
• GTA demonstrates anti-inflammatory and neuroprotective potential by attenuating neuroglial activation and increasing ChAT immunoreactivity in neuroinflammation models.