Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR-122 in rats
Article first published online: 11 SEP 2012
© 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
Molecular Nutrition & Food Research
Volume 56, Issue 11, pages 1636–1646, November 2012
How to Cite
Baselga-Escudero, L., Bladé, C., Ribas-Latre, A., Casanova, E., Salvadó, M. J., Arola, L. and Arola-Arnal, A. (2012), Grape seed proanthocyanidins repress the hepatic lipid regulators miR-33 and miR-122 in rats. Mol. Nutr. Food Res., 56: 1636–1646. doi: 10.1002/mnfr.201200237
- Issue published online: 24 OCT 2012
- Article first published online: 11 SEP 2012
- Manuscript Accepted: 31 JUL 2012
- Manuscript Revised: 19 JUL 2012
- Manuscript Received: 24 APR 2012
- Spanish Government. Grant Number: AGL 2008–00387/ALI
- European Union Seventh Framework Programme. Grant Number: 244995
One major health problem in westernized countries is dysregulated fatty acid and cholesterol metabolism that causes pathologies such as metabolic syndrome. Previous studies from our group have shown that proanthocyanidins, which are the most abundant polyphenols in the human diet, regulate lipid metabolism and are potent hypolipidemic agents. The noncoding RNAs, miR-33 and miR-122, regulate genes that are involved in lipid metabolism.
Methods and results
Here, we show that grape seed proanthocyanidins rapidly and transiently repressed the expression of miR-33 and miR-122 in rat hepatocytes in vivo and in vitro. Furthermore, the miR-33 target gene ATP-binding cassette A1 and the miR-122 target gene fatty acid synthase were also modulated by proanthocyanidins. Specifically, ATP-binding cassette A1 mRNA and protein levels were increased, and fatty acid synthase mRNA and protein levels were reduced after the miRNA levels were altered.
These results suggest that proanthocyanidin treatment increased hepatic cholesterol efflux to produce new HDL particles by repressing miR-33, and it reduced lipogenesis by repressing miR-122. These results highlight a new mechanism by which grape seed proanthocyanidins produce hypolipidemia through their effects on miRNA modulators of lipid metabolism.