A grape seed procyanidin extract inhibits HDAC activity leading to increased Pparα phosphorylation and target-gene expression.
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.



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, Pparα activity and target-gene expression, and serum lipid levels.



GSPE increased histone acetylation and decreased Class I HDAC activity in vivo, and dose-dependently inhibited recombinant HDAC2 and 3 activities in vitro. Accordingly, Pparα gene and phosphorylated protein expression were increased, as were target genes involved in fatty acid catabolism, suggesting increased Pparα activity. Serum fibroblast growth factor 21 (Fgf21) was elevated, and triglyceride levels were reduced by 28%.



GSPE regulates HDAC and Pparα activities to modulate lipid catabolism and reduce serum triglycerides in vivo.
Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA.
Laura E
LE
Downing
Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA.
Bradley S
BS
Ferguson
Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA.
Kelvin
K
Rodriguez
Department of Agriculture, Nutrition and Veterinary Sciences, University of Nevada Reno, Reno, NV, USA.
Marie-Louise
ML
Ricketts
D000107:Acetylation / Q000187:drug effects; D000818:Animals; D000072040:Apolipoprotein A-V / Q000235:genetics; D044946:Biflavonoids / Q000494:pharmacology*; D002392:Catechin / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005346:Fibroblast Growth Factors / Q000097:blood / Q000235:genetics; D056604:Grape Seed Extract / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D056464:Histone Deacetylase 2 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D056572:Histone Deacetylase Inhibitors / Q000494:pharmacology*; D006655:Histone Deacetylases / Q000378:metabolism; D006657:Histones / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D047493:PPAR alpha / Q000378:metabolism*; D010766:Phosphorylation / Q000187:drug effects; D044945:Proanthocyanidins / Q000494:pharmacology*; D014280:Triglycerides / Q000097:blood
C499058:Apoa5 protein, mouse; D000072040:Apolipoprotein A-V; D044946:Biflavonoids; D056604:Grape Seed Extract; D056572:Histone Deacetylase Inhibitors; D006657:Histones; D047493:PPAR alpha; D044945:Proanthocyanidins; D014280:Triglycerides; C414620:fibroblast growth factor 21; C017674:procyanidin; D005346:Fibroblast Growth Factors; D002392:Catechin; D056464:Histone Deacetylase 2; D006655:Histone Deacetylases
Fgf21; HDAC; Pparα; Procyanidins; Triglycerides