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

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

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.

Publication types

  • Comparative Study

MeSH terms

  • 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
  • Lipid Metabolism / physiology*
  • Liver / cytology
  • Liver / metabolism*
  • Mice
  • MicroRNAs / antagonists & inhibitors*
  • MicroRNAs / metabolism*
  • Microarray Analysis
  • Molecular Sequence Data
  • Multienzyme Complexes / metabolism
  • Obesity / metabolism*
  • Oligonucleotides, Antisense / genetics
  • Oligonucleotides, Antisense / pharmacology*
  • Protein-Serine-Threonine Kinases / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction

Substances

  • DNA Primers
  • Fatty Acids
  • MicroRNAs
  • Multienzyme Complexes
  • Oligonucleotides, Antisense
  • Cholesterol
  • Protein-Serine-Threonine Kinases
  • AMP-Activated Protein Kinases

Associated data

  • GEO/GSE3603