title: Down-regulation of Risa improves insulin sensitivity by enhancing autophagy.
abstract: 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 Gsk3β, 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.
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Yuangao
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Yanan
authors.initials: Y
authors.lastname: Hu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Chenxia
authors.initials: C
authors.lastname: Sun
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Shu
authors.initials: S
authors.lastname: Zhuo
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Zhishui
authors.initials: Z
authors.lastname: He
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Hui
authors.initials: H
authors.lastname: Wang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Menghong
authors.initials: M
authors.lastname: Yan
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Jun
authors.initials: J
authors.lastname: Liu
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Yi
authors.initials: Y
authors.lastname: Luan
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Changgui
authors.initials: C
authors.lastname: Dai
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Yonggang
authors.initials: Y
authors.lastname: Yang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Rui
authors.initials: R
authors.lastname: Huang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Ben
authors.initials: B
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and.
authors.forename: Fang
authors.initials: F
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Nutrition and Metabolism, CAS Center for Excellence in Molecular Cell Science, Institute for Nutritional Sciences, Shanghai Institutes for Biological Sciences, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, China; and School of Life Science and Technology, ShanghaiTech University, Shanghai, China qwzhai@sibs.ac.cn.
authors.forename: Qiwei
authors.initials: Q
authors.lastname: Zhai
mesh_terms: D000818:Animals; D001343:Autophagy / Q000502:physiology*; D015536:Down-Regulation / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology*; D055785:Gene Knockdown Techniques; D007333:Insulin Resistance / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D062085:RNA, Long Noncoding / Q000235:genetics / Q000378:metabolism*
chemical_list: D062085:RNA, Long Noncoding
keywords: glucose homeostasis; insulin resistance; lncRNA; ob/ob mice