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Grape seed proanthocyanidins repress the hepatic lipid regulators miR‐33 and miR‐122 in rats
Author(s) -
BaselgaEscudero Laura,
Bladé Cinta,
RibasLatre Aleix,
Casanova Ester,
Salvadó M. Josepa,
Arola Lluis,
ArolaArnal Anna
Publication year - 2012
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201200237
Subject(s) - proanthocyanidin , lipid metabolism , fatty acid synthase , biochemistry , lipogenesis , grape seed extract , biology , abca1 , fatty acid , polyphenol , chemistry , gene , antioxidant , medicine , alternative medicine , pathology , transporter
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.