Acutely administered grape-seed proanthocyanidin extract acts as a satiating agent

Abstract

Grape-seed proanthocyanidins' role as stimulators of active GLP-1 in rats suggests that they could be effective as satiating agents. Wistar rats were used to study the effects of proanthocyanidins on food intake with different doses, administration times and proanthocyanidin extract compositions. A dose of 423 mg of phenolics per kg body weight (BW) of grape-seed proanthocyanidin extract (GSPE) was necessary to decrease the 12-hour cumulative food intake by 18.7 ± 3.4%. Proanthocyanidins were effective when delivered directly into the gastrointestinal tract one hour before, or simultaneously at the start of the feeding period. Proanthocyanidins without galloyl forms, such as those from cocoa extract, were not as effective as grape-seed derived forms. GSPE increased the portal levels of active GLP-1 and total ghrelin and decreased the CCK levels, simultaneously with a decrease in gastric emptying. In conclusion, grape-seed proanthocyanidins could be useful as a satiating agent under the conditions defined in this study.

Defining Conditions for Optimal Inhibition of Food Intake in Rats by a Grape-Seed Derived Proanthocyanidin Extract

“…Given that GSPE was effective in increasing active GLP-1 levels [36] at doses inhibiting food intake [17], we checked the role of GLP-1 in this effect on food intake. Figure 3a shows that the short-term effects of GSPE on food intake were antagonized by the GLP-1 receptor (GLP-1-R) antagonist Ex9 [29], as was the case with i.p.…”

“…We initially defined the inhibitory effect of GSPE on food intake in female, male, young, aged, normofagic and hyperfagic animals after an acute treatment [17]. Afterwards, we showed that a specific dose is needed to ensure a significant chronic effect on body weight control [14].…”

“…Regarding the optimal dose, we initially proved that the inhibition on food intake could be obtained by the GSPE dose, which caused an increase in GLP-1 levels, 1 g GSPE/kg BW; we then proved that GSPE at a dose of 500 mg of GSPE extract/kg of body weight is the optimal dose [17]. However, since several studies have failed to find any effect on food intake at lower doses, we considered it necessary to determine the range of doses that could inhibit food intake.…”

“…Parallel controls were performed by intragastrically administering the vehicle. This experiment was conducted on animals on a standard chow diet and on animals receiving hypercaloric meals as detailed in [17]. …”

“…We ruled out the possibility that proanthocyanidins were playing an important role in inhibiting the gastrointestinal digestion process [14]. Remarkably, the animals ingested less food, which could be due to the changes induced by the extract on enteroendocrine signals (increased active GLP-1 [17] and decreased acylated ghrelin [18]) and/or by other signals that limit their need to feeding [17]. Bao et al, working with GSPE in diabetic rats and at doses similar to ours, also found an inhibition in food intake after chronic administration [19].…”