Long-Lasting Effects of GSPE on Ileal GLP-1R Gene Expression Are Associated with a Hypomethylation of the GLP-1R Promoter in Female Wistar Rats.

Abstract

Flavonoids have been shown to modulate GLP-1 in obesity. GLP-1 induces some of its effects through the intestinal GLP-1 receptor (GLP-1R), though no data exist on how flavonoids affect this receptor. Here, we examine how a dose of grape seed proanthocyanidin extract (GSPE) with anti-obesity activity affects intestinal GLP-1R and analyze whether epigenetics play a role in the long-lasting effects of GSPE. We found that 10-day GSPE administration prior to the cafeteria diet upregulated GLP-1R mRNA in the ileum 17 weeks after the GSPE treatment. This was associated with a hypomethylation of the GLP-1R promoter near the region where the SP1 transcription factor binds. In the colon, the cafeteria diet upregulated GLP-1R without showing any GSPE effect. In conclusion, we have identified long-lasting GSPE effects on GLP-1R gene expression in the ileum that are partly mediated by hypomethylation at the gene promoter and may affect the SP1 binding factor.

• Authors: Iris Ginés, Katherine Gil-Cardoso, Claudio D'Addario, Anastasia Falconi, Fabio Bellia, M Teresa Blay, Ximena Terra, Anna Ardévol, Montserrat Pinent, Raúl Beltrán-Debón
• Journal: Biomolecules (Biomolecules) Vol. 9 Issue 12 (12 12 2019) ISSN: 2218-273X [Electronic] Switzerland
• PMID: 31842341 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glucagon-Like Peptide-1 Receptor
• Grape Seed Extract
• Grape Seed Proanthocyanidins
• Plant Extracts
• Proanthocyanidins
• RNA, Messenger

Topics

• Animals
• DNA Methylation (drug effects)
• Female
• Glucagon-Like Peptide-1 Receptor (genetics, metabolism)
• Grape Seed Extract (administration & dosage, chemistry, pharmacology)
• Ileum (drug effects, metabolism)
• Intestinal Mucosa (drug effects, metabolism)
• Plant Extracts (administration & dosage, chemistry, pharmacology)
• Proanthocyanidins (administration & dosage, chemistry, pharmacology)
• Promoter Regions, Genetic (genetics)
• RNA, Messenger (genetics, metabolism)
• Rats
• Rats, Wistar
• Up-Regulation (drug effects)