Down-regulation of Risa improves insulin sensitivity by enhancing autophagy

被引：34

作者：

Wang, Yuangao ^{[1
]}

Hu, Yanan ^{[1
]}

Sun, Chenxia ^{[1
]}

Zhuo, Shu ^{[1
]}

He, Zhishui ^{[1
]}

Wang, Hui ^{[1
]}

Yan, Menghong ^{[1
]}

Liu, Jun ^{[1
]}

Luan, Yi ^{[1
]}

Dai, Changgui ^{[1
]}

Yang, Yonggang ^{[1
]}

Huang, Rui ^{[1
]}

Zhou, Ben ^{[1
]}

Zhang, Fang ^{[1
]}

Zhai, Qiwei ^{[1
,2
]}

机构：

[1] Chinese Acad Sci, Univ Chinese Acad Sci, CAS Ctr Excellence Mol Cell Sci,Inst Nutr Sci, Key Lab Nutr & Metab,Shanghai Inst Biol Sci, Shanghai, Peoples R China

[2] ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai, Peoples R China

来源：

FASEB JOURNAL | 2016年 / 30卷 / 09期

基金：

中国国家自然科学基金;

关键词：

lncRNA; insulin resistance; glucose homeostasis; ob; ob mice; LONG NONCODING RNAS; ACTIVATES AUTOPHAGY; SIRT1; PHOSPHORYLATION; METABOLISM; OBESITY; STRESS; OVEREXPRESSION; EXPRESSION; SELECTION;

D O I：

10.1096/fj.201500058R

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

It has been reported that some small noncoding RNAs are involved in the regulation of 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 Gsk3, 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.

引用

页码：3133 / 3145

页数：13

共 54 条

[1] NAR Breakthrough Article 7SL RNA represses p53 translation by competing with HuR [J].