miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
- PMID: 16459310
- DOI: 10.1016/j.cmet.2006.01.005
miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
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.
Similar articles
-
Reduction of JNK1 expression with antisense oligonucleotide improves adiposity in obese mice.Am J Physiol Endocrinol Metab. 2008 Aug;295(2):E436-45. doi: 10.1152/ajpendo.00629.2007. Epub 2008 Jun 3. Am J Physiol Endocrinol Metab. 2008. PMID: 18523126
-
MicroRNA expression signature and antisense-mediated depletion reveal an essential role of MicroRNA in vascular neointimal lesion formation.Circ Res. 2007 Jun 8;100(11):1579-88. doi: 10.1161/CIRCRESAHA.106.141986. Epub 2007 May 3. Circ Res. 2007. PMID: 17478730
-
The up-regulation of microRNA-335 is associated with lipid metabolism in liver and white adipose tissue of genetically obese mice.Biochem Biophys Res Commun. 2009 Aug 7;385(4):492-6. doi: 10.1016/j.bbrc.2009.05.058. Epub 2009 May 19. Biochem Biophys Res Commun. 2009. PMID: 19460359
-
AMP-activated protein kinase: Role in metabolism and therapeutic implications.Diabetes Obes Metab. 2006 Nov;8(6):591-602. doi: 10.1111/j.1463-1326.2005.00561.x. Diabetes Obes Metab. 2006. PMID: 17026483 Review.
-
Role of malonyl-CoA in heart disease and the hypothalamic control of obesity.Cardiovasc Res. 2007 Jan 15;73(2):278-87. doi: 10.1016/j.cardiores.2006.10.008. Epub 2006 Oct 20. Cardiovasc Res. 2007. PMID: 17126822 Review.
Cited by
-
Therapeutic Potential of miRNAs for Type 2 Diabetes Mellitus: An Overview.Epigenet Insights. 2022 Oct 15;15:25168657221130041. doi: 10.1177/25168657221130041. eCollection 2022. Epigenet Insights. 2022. PMID: 36262691 Free PMC article. Review.
-
Transcriptomic Analysis Reveals the Effects of miR-122 Overexpression in the Liver of Qingyuan Partridge Chickens.Animals (Basel). 2024 Jul 22;14(14):2132. doi: 10.3390/ani14142132. Animals (Basel). 2024. PMID: 39061594 Free PMC article.
-
Characteristics and expression profiles of circRNAs during abdominal adipose tissue development in Chinese Gushi chickens.PLoS One. 2021 Apr 15;16(4):e0249288. doi: 10.1371/journal.pone.0249288. eCollection 2021. PLoS One. 2021. PMID: 33857153 Free PMC article.
-
Predicting Nonalcoholic Fatty Liver Disease through a Panel of Plasma Biomarkers and MicroRNAs in Female West Virginia Population.Int J Mol Sci. 2020 Sep 13;21(18):6698. doi: 10.3390/ijms21186698. Int J Mol Sci. 2020. PMID: 32933141 Free PMC article.
-
Interplay of mitochondrial metabolism and microRNAs.Cell Mol Life Sci. 2017 Feb;74(4):631-646. doi: 10.1007/s00018-016-2342-7. Epub 2016 Aug 25. Cell Mol Life Sci. 2017. PMID: 27563705 Free PMC article. Review.
Publication types
MeSH terms
Substances
Associated data
- Actions
LinkOut - more resources
Full Text Sources
Other Literature Sources
Medical
Molecular Biology Databases