A grape seed procyanidin extract inhibits HDAC activity leading to increased Ppar[alpha] phosphorylation and target-gene expression

Scope Histone deacetylases (HDACs) have emerged as epigenetic regulators of risk factors associated with the metabolic syndrome (MetS), and certain botanical extracts have proven to be potent HDAC inhibitors. Understanding the role of dietary procyanidins in HDAC inhibition is important in exploring the therapeutic potential of natural products. Methods C57BL/6 mice were gavaged with vehicle (water) or grape seed procyanidin extract (GSPE, 250 mg/kg) and terminated 14 h later. Liver and serum were harvested to assess the effect of GSPE on HDAC activity, histone acetylation, Ppar[alpha] activity and target-gene expression, and serum lipid levels. Results GSPE increased histone acetylation and decreased Class I HDAC activity in vivo, and dose-dependently inhibited recombinant HDAC2 and 3 activities in vitro. Accordingly, Ppar[alpha] gene and phosphorylated protein expression were increased, as were target genes involved in fatty acid catabolism, suggesting increased Ppar[alpha] activity. Serum fibroblast growth factor 21 (Fgf21) was elevated, and triglyceride levels were reduced by 28%. Conclusion GSPE regulates HDAC and Ppar[alpha] activities to modulate lipid catabolism and reduce serum triglycerides in vivo.