Down-regulation of Risa improves insulin sensitivity by enhancing autophagy

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作者:Yuangao Wang,* Yanan Hu,* Chenxia Sun,* Shu Zhuo,* Zhishui He,* Hui Wang,* Menghong Yan,* Jun Liu,* Yi Luan,* Changgui Dai,* Yonggang Yang,* Rui Huang,* Ben Zhou,* Fang Zhang,* and Qiwei Zhai*,†,1

The FASEB Journal 卷:30 期:9 页:3133-3145  发表年份:2016

摘要:It has been reported that some smal lnoncoding RNAs are involved in the regulationof insulin sensitivity.However, whether long noncoding RNAs also participate in the regulation of insulin sensitivity is still largely unknown. We identified and characterized a long noncoding RNA, regulator of insulin sensitivity and autophagy(Risa), which is a poly(A)+ cytoplasmic RNA. Overexpression of Risa in mouse primary hepatocytes or C2C12 myotubes attenuated insulin-stimulated phosphorylation of insulin receptor, Akt, and Gsk3b, and knockdown of Risa alleviated insulin resistance. Further studies showed that overexpression of Risa in hepatocytes or myotubes decreased autophagy, and knockdown of Risa up-regulated autophagy. Moreover, knockdown of Atg7 or -5 significantly inhibited the effect of knockdown of Risa on insulin resistance, suggesting that knockdown of Risa alleviated insulin resistance via enhancing autophagy. In addition, tail vein injection of adenovirus to knock down Risa enhanced insulin sensitivity and hepatic autophagy in both C57BL/6 and ob/ob mice. Taken together, the data demonstrate that Risa regulates insulin sensitivity by affecting autophagy and suggest that Risa is a potential target for treating insulin-resistance–related diseases.—Wang, Y., Hu, Y., Sun, C., Zhuo, S., He, Z.,Wang, H., Yan,M., Liu,J., Luan, Y., Dai, C., Yang, Y., Huang, R., Zhou, B., Zhang, F., Zhai, Q. Down-regulation of Risa improves insulin sensitivity by enhancing autophagy.FASEB J. 30, 3133–3145 (2016). www.fasebj.org