Search

MicroRNAs (miRNAs) are small noncoding RNAs, approximately 18-25 nucleotides in length, that modulate gene expression at the posttranscriptional level. Thousands of miRNAs have been described, and it is thought that they regulate some aspects of more than 60% of all human cell transcripts. Several polyphenols have been shown to modulate miRNAs related to metabolic homeostasis and chronic diseases. Polyphenolic modulation of miRNAs is very attractive as a strategy to target numerous cell processes and potentially reduce the risk of chronic disease. Evidence is building that polyphenols can target specific miRNAs, such as miR-122, but more studies are necessary to discover and validate additional miRNA targets.

Scope 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. Conclusion 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.