Co‐administration of a Grape Seed Procyanidin Extract and the Bile Acid Sequestrant, Cholestyramine, Results in Beneficial Metabolic Alterations, Including Decreased Triglyceride Levels

Abstract

Bile acid (BA) sequestrants, used to lower cholesterol levels, may be taken alone or in combination with cholesterol‐lowering medication. We previously showed that grape seed procyanidin extract (GSPE) reduces enterohepatic BA recirculation as a new mechanism to reduce serum triglyceride (TG) levels. This study aimed to determine the effects of co‐administering an acute dose of GSPE with the BA‐binding resin cholestyramine (CHY) on TG levels and BA homeostatic gene expression.
 Eight‐week old C57BL/6 mice were treated for 4 weeks with a control diet, or a 2% CHY‐supplemented diet, after which, they were administered vehicle or GSPE (250mg/kg) for 14 hours. Tissues were harvested and gene expression levels were analyzed via qPCR. Biochemical analysis was performed to assess serum BA and TG levels. Data were analyzed using one‐way ANOVA.
 Results show that CHY‐GSPE co‐administration reduces intestinal IBABP (61%, p<0.0001) and FGF15 (99.5%, p<0.0001) expression, relative to control. In addition serum BA levels were decreased 74% (p<0.0001), while hepatic CYP7A1 expression was increased 13‐fold (p<0.0001), indicative of increased BA synthesis. SREBP1c expression was reduced 42% and serum TG levels were decreased 34% in the CHY‐GSPE group, compared to control.
 We present novel evidence showing that GSPE works synergistically with CHY to lower serum TG levels, which is achieved via enhanced de novo BA biosynthesis.