miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
miR-122 regulation of lipid metabolism revealed by in vivo antisense targeting
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DOI：
10.1016/j.cmet.2006.01.005
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发表时间：
2006-02-01
期刊：
影响因子：
29
通讯作者：
Monia, BP
中科院分区：
文献类型：
--
作者：
Esau, C;Davis, S;Monia, BP
目前对microRNA(MiRNA)生物学的了解是有限的，而反义寡核苷酸(ASO)抑制miRNAs是实现其功能化的有力手段。为了揭示肝脏特异性miR-122在成年肝脏中的作用，我们用2‘-O-甲氧乙基硫代磷酸ASO抑制了它。抑制正常小鼠的MIR-122导致血浆胆固醇水平降低，肝脏脂肪酸氧化增加，肝脏脂肪酸和胆固醇合成率下降。中枢代谢感受器AMPK的激活也增加。在饮食诱导的肥胖小鼠模型中，抑制MIR-122导致血浆胆固醇水平下降，肝脏脂肪变性显著改善，并伴随着几个造脂基因的减少。这些结果表明miR-122是成人肝脏胆固醇和脂肪酸代谢的关键调节因子，并提示miR-122可能是治疗代谢性疾病的一个有吸引力的靶点。
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.