title: Acetate supplementation increases brain histone acetylation and inhibits histone deacetylase activity and expression.
abstract: Acetate supplementation increases brain, heart, and liver acetyl-CoA levels and reduces lipopolysaccharide-induced neuroinflammation. Because intracellular acetyl-CoA can be used to alter histone acetylation-state, using Western blot analysis, we measured the temporal effect that acetate supplementation had on brain and liver histone acetylation following a single oral dose of glyceryl triacetate (6 g/kg). In parallel experiments, we measured the effect that acetate supplementation had on histone deacetylase (HDAC) and histone acetyltransferase (HAT) enzymic activities and the expression levels of HDAC class I and II enzymes using Western blot analysis. We found that acetate supplementation increased the acetylation-state of brain histone H4 at lysine 8 at 2 and 4 h, histone H4 at lysine 16 at 4 and 24 h, and histone H3 at lysine 9 at 4 h following treatment. No changes in other forms of brain or liver H3 and H4 acetylation-state were found at any post-treatment times measured. Enzymic HAT and HDAC assays on brain extracts showed that acetate supplementation had no effect on HAT activity, but significantly inhibited by 2-fold HDAC activity at 2 and 4 h post-treatment. Western blot analysis demonstrated that HDAC 2 levels were decreased at 4 h following treatment. Based on these results, we conclude that acetyl-CoA derived from acetate supplementation increases brain histone acetylation-state by reducing HDAC activity and expression.
authors.affiliation: Department of Pharmacology, Physiology, and Therapeutics, School of Medicine and Health Sciences, University of North Dakota, Grand Forks, ND 58203, USA.
authors.forename: Mahmoud L
authors.initials: ML
authors.lastname: Soliman
authors.forename: Thad A
authors.initials: TA
authors.lastname: Rosenberger
mesh_terms: D000085:Acetates / Q000008:administration & dosage*; D000107:Acetylation; D000818:Animals; D015153:Blotting, Western; D001921:Brain / Q000201:enzymology / Q000378:metabolism*; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism*; D006657:Histones / Q000378:metabolism*; D008099:Liver / Q000201:enzymology / Q000378:metabolism; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley
chemical_list: D000085:Acetates; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D006655:Histone Deacetylases