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Cell Metab ; 3(2): 87-98, 2006 Feb.
Article in English | MEDLINE | ID: mdl-16459310

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.


Subject(s)
Lipid Metabolism/physiology , Liver/metabolism , MicroRNAs/antagonists & inhibitors , MicroRNAs/metabolism , Obesity/metabolism , Oligonucleotides, Antisense/pharmacology , AMP-Activated Protein Kinases , Animals , Blood Chemical Analysis , Blotting, Northern , Blotting, Western , Cell Line , Cholesterol/blood , Chromatography, High Pressure Liquid , DNA Primers , Enzyme Activation/drug effects , Fatty Acids/metabolism , Gene Expression Regulation/drug effects , Liver/cytology , Mice , Microarray Analysis , Molecular Sequence Data , Multienzyme Complexes/metabolism , Oligonucleotides, Antisense/genetics , Protein Serine-Threonine Kinases/metabolism , Reverse Transcriptase Polymerase Chain Reaction
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