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

被引：1945

作者：

Esau, C ^{[1
]}

Davis, S ^{[1
]}

Murray, SF ^{[1
]}

Yu, XX ^{[1
]}

Pandey, SK ^{[1
]}

Pear, M ^{[1
]}

Watts, L ^{[1
]}

Booten, SL ^{[1
]}

Graham, M ^{[1
]}

McKay, R ^{[1
]}

Subramaniam, A ^{[1
]}

Propp, S ^{[1
]}

Lollo, BA ^{[1
]}

Freier, S ^{[1
]}

Bennett, CF ^{[1
]}

Bhanot, S ^{[1
]}

Monia, BP ^{[1
]}

机构：

[1] ISIS Pharmaceut, Carlsbad, CA 92008 USA

来源：

CELL METABOLISM | 2006年 / 3卷 / 02期

关键词：

D O I：

10.1016/j.cmet.2006.01.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

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.

引用

页码：87 / 98

页数：12

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