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

نویسندگان

  • Christine Esau
  • Scott Davis
  • Susan F Murray
  • Xing Xian Yu
  • Sanjay K Pandey
  • Michael Pear
  • Lynnetta Watts
  • Sheri L Booten
  • Mark Graham
  • Robert McKay
  • Amuthakannan Subramaniam
  • Stephanie Propp
  • Bridget A Lollo
  • Susan Freier
  • C Frank Bennett
  • Sanjay Bhanot
  • Brett P Monia
چکیده

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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عنوان ژورنال:
  • Cell metabolism

دوره 3 2  شماره 

صفحات  -

تاریخ انتشار 2006