Inhibition of miR-29 has a significant lipid-lowering benefit through suppression of lipogenic programs in liver

ABSTRACT: MicroRNAs (miRNAs) are important regulators and potential therapeutic targets of metabolic disease. In this study we show by in vivo administration of locked nucleic acid (LNA) inhibitors that suppression of endogenous miR-29 lowers plasma cholesterol levels by ~40%, commensurate with the effect of statins, and reduces fatty acid content in the liver by ~20%. Whole transcriptome sequencing of the liver reveals 883 genes dysregulated (612 down, 271 up) by inhibition of miR-29. The set of 612 down-regulated genes are most significantly over-represented in lipid synthesis pathways. Among the up-regulated genes are the anti-lipogenic deacetylase sirtuin 1 (Sirt1) and the anti-lipogenic transcription factor aryl hydrocarbon receptor (Ahr), the latter of which we demonstrate is a direct target o

ORGANISM(S): Mus musculus

SUBMITTER: Praveen Sethupathy 

PROVIDER: E-GEOD-63493 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress