Long Term Exposure to a Grape Seed Proanthocyanidin Extract Enhances L-Cell Differentiation in Intestinal Organoids.

SCOPE A grape-seed proanthocyanidin extract (GSPE) interacts at the intestinal level, enhancing glucagon-like peptide-1 (GLP-1) and peptide YY (PYY) release, which modulate appetite and glucose homeostasis. Thus, enhancing L-cell numbers could be a strategy to promote hormone production, providing a potential strategy for obesity and type-2 diabetes mellitus treatment. METHODS & RESULTS Mice ileum organoids were used to evaluate the long-term effects of GSPE and two of its main components, epicatechin (EC) and gallic acid (GA), on intestinal differentiation. Hormone levels were determined using RIA and ELISA kits, and gene expression of transcription factors involved in intestinal cell differentiation, as well as markers of different cell types, were assessed by real-time qPCR. GSPE up-regulated enterohormone gene expression and content, as well as the pan-endocrine marker ChgA. GSPE also modulated the temporal gene expression profile of early and late transcription factors involved in L-cell differentiation. Furthermore, GSPE up-regulated goblet cell (Muc2) and enterocyte (SIS) markers, while down-regulating stem cell markers (Lgr5+). Although EC and GA modified enterohormone release, they did not reproduce GSPE effects on transcription factor's profile. CONCLUSIONS This study shows the potential role of GSPE in promoting enteroendocrine differentiation, effect that is not mediated by EC or GA. This article is protected by copyright. All rights reserved.