Dietary procyanidins lower serum triglyceride levels via up‐regulation in Pparα and its downstream target gene expression

Abstract

Hypertriglyceridemia is an independent risk factor for cardiovascular disease. We previously demonstrated that a grape seed procyanidin extract (GSPE) reduces serum triglycerides (TG) in normolipidemic mice and dyslipidemic rats. The current study aimed to identify additional molecular mechanisms underlying the TG‐lowering effect of GSPE.Eight‐week old C57BL/6 mice were fed a standard rodent chow and administered vehicle (water) or GSPE (250 mg/kg) for 14 hours. Following termination, blood was collected and biochemical analyses were performed to assess serum TG and fibroblast growth factor 21 (Fgf21) levels. Liver was harvested and gene expression was analyzed via qPCR. Statistical significance was determined using a student's t‐test.GSPE increased peroxisome proliferator‐activated receptor alpha (Pparα) expression (82%, p<0.05) and several target‐genes, including Fgf21 (eight‐fold, p<0.01), Cpt1a (40%, p<0.01), and ApoA5 (62%, p<0.05). In agreement with these results, serum Fgf21 levels were increased eight‐fold (p<0.05), compared to control, while TG levels were reduced (28%, p<0.001). Additionally, bile acid (BA) biosynthetic gene expression was up‐regulated, in particular Cyp7a1 expression was increased five‐fold (p<0.0001), indicative of increased BA synthesis in the presence of GSPE. Pparα target genes involved in biliary cholesterol excretion were also increased in the presence of GSPE (Abcg5/8, 47% and 42%, respectively, p<0.01), as was fecal cholesterol excretion (7.5%, p<0.05).In conclusion, we propose that GSPE increases BA biosynthesis, which then increases Pparα expression, facilitating increased expression of Fgf21 and genes associated with fatty acid oxidation, ultimately leading to increased TG catabolism and reduced serum TG levels. Pparα activation also leads to increased biliary cholesterol excretion and fecal cholesterol content.Support or Funding InformationFunding provided by USDA‐Hatch project NEV0749