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

@article{citeulike:498727, 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.}, address = {Isis Pharmaceuticals, 1896 Rutherford Road, Carlsbad, California 92008.}, author = {Esau, C. and Davis, S. and Murray, S. F. and Yu, X. X. and Pandey, S. K. and Pear, M. and Watts, L. and Booten, S. L. and Graham, M. and McKay, R. and Subramaniam, A. and Propp, S. and Lollo, B. A. and Freier, S. and Bennett, C. F. and Bhanot, S. and Monia, B. P. }, citeulike-article-id = {498727}, doi = {10.1016/j.cmet.2006.01.005}, issn = {1550-4131}, journal = {Cell Metab}, keywords = {antimicrorna, microrna, microrna\_microarray}, month = {February}, number = {2}, pages = {87--98}, posted-at = {2008-01-24 17:27:52}, priority = {3}, title = {miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting.}, url = {http://dx.doi.org/10.1016/j.cmet.2006.01.005}, volume = {3}, year = {2006} }

TY - JOUR ID - citeulike:498727 L3 - citeulike-article-id:498727 TI - miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting. JF - Cell Metab VL - 3 IS - 2 SP - 87 EP - 98 AD - Isis Pharmaceuticals, 1896 Rutherford Road, Carlsbad, California 92008. SN - 1550-4131 N2 - 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. KW - antimicrorna KW - microrna KW - microrna_microarray AU - Esau, C AU - Davis, S AU - Murray, SF AU - Yu, XX AU - Pandey, SK AU - Pear, M AU - Watts, L AU - Booten, SL AU - Graham, M AU - McKay, R AU - Subramaniam, A AU - Propp, S AU - Lollo, BA AU - Freier, S AU - Bennett, CF AU - Bhanot, S AU - Monia, BP PY - 2006/02// UR - http://dx.doi.org/10.1016/j.cmet.2006.01.005 ER -