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Comparative Study
. 2006 Feb;3(2):87-98.
doi: 10.1016/j.cmet.2006.01.005.

miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting

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Free article
Comparative Study

miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting

Christine Esau et al. Cell Metab. 2006 Feb.
Free article

Abstract

Current understanding of microRNA (miRNA) biology is limited, and antisense oligonucleotide (ASO) inhibition of miRNAs is a powerful technique for their functionalization. To uncover the role of the liver-specific miR-122 in the adult liver, we inhibited it in mice with a 2'-O-methoxyethyl phosphorothioate ASO. miR-122 inhibition in normal mice resulted in reduced plasma cholesterol levels, increased hepatic fatty-acid oxidation, and a decrease in hepatic fatty-acid and cholesterol synthesis rates. Activation of the central metabolic sensor AMPK was also increased. miR-122 inhibition in a diet-induced obesity mouse model resulted in decreased plasma cholesterol levels and a significant improvement in liver steatosis, accompanied by reductions in several lipogenic genes. These results implicate miR-122 as a key regulator of cholesterol and fatty-acid metabolism in the adult liver and suggest that miR-122 may be an attractive therapeutic target for metabolic disease.

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