Modulation of mir-33 and mir-122 by dietary polyphenols

Identificador:  TDX:1257

Handle: https://hdl.handle.net/20.500.11797/TDX1257

Autors:  Baselga Escudero, Laura

Resum:
mi(cro)RNAs are becoming relevant for the epigenetic control of metabolism. miRNAs are small non-conding RNAs of approximately 19-24 nucleotides in length that regulate the expression of target genes at post-transcriptional level. Specifically, miR-33 is a critical regulator of cholesterol and fatty acid homeostasis by repressesing fatty acid oxidation, hepatic HDL biogenesis and cholesterol efflux to HDL. Furthermore, miR-122, which is liver-specific, regulates several genes that control fatty acid and triglyceride biosynthesis. On the other hand, dietary components, such polyphenols, are reported to have benefitial effects againts cardiovascular diseases, reducing triglycerides and/or cholesterol plasma levels. Hence, the main objective of this thesis was to evaluate the capacity of polyphenols, mainly proanthocyanidins, to modulate miR-33 and miR-122 in different physiological situations. Result showed that polyphenols modulate these miRNAs and their target genes in liver, suggesting that miRNAs regulation are a new molecular mechanims used by some polyphenols to modulate lipid metabolism and to improve the atherogenic profile. Moreover, NMR studies showed that polyphenols directly bind to miR-33 and miR-122, suggesting that polyphenols can modulate cell miRNAs levels by a direct interaction.